{"id":5171,"date":"2024-01-16T11:01:40","date_gmt":"2024-01-16T11:01:40","guid":{"rendered":"https:\/\/farlong.com\/?p=5171"},"modified":"2024-01-27T10:30:11","modified_gmt":"2024-01-27T10:30:11","slug":"research-progress-on-pyroptosis-mediated-immune-inflammatory-response-in-ischemic-stroke-and-the-role-of-natural-plant-components-as-regulator-of-pyroptosis-a-review","status":"publish","type":"post","link":"https:\/\/directcm.com\/fr\/research-progress-on-pyroptosis-mediated-immune-inflammatory-response-in-ischemic-stroke-and-the-role-of-natural-plant-components-as-regulator-of-pyroptosis-a-review\/","title":{"rendered":"Progr\u00e8s de la recherche sur la r\u00e9ponse immuno-inflammatoire m\u00e9di\u00e9e par la pyroptose dans les accidents vasculaires c\u00e9r\u00e9braux isch\u00e9miques et le r\u00f4le des composants naturels des plantes en tant que r\u00e9gulateurs de la pyroptose\u00a0: une revue"},"content":{"rendered":"<div id=\"ab0015\" class=\"abstract author-highlights\">\n<h2 class=\"section-title u-h4 u-margin-l-top u-margin-xs-bottom\">Highlights<\/h2>\n<div id=\"abs0015\">\n<ul>\n<li id=\"p0005\">This review summarized the latest molecular mechanism of pyroptosis on ischemic stroke.<\/li>\n<li id=\"p0010\">This review summarizes the role of natural plant components as regulator of pyroptosis in ischemic stroke<\/li>\n<li id=\"p0015\">Regulation of pyroptosis in ischemic stroke is proposed as a potential therapeutic strategy.<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<div id=\"ab0010\" class=\"abstract author\"><\/p>\n<h2><\/h2>\n<h2 class=\"section-title u-h4 u-margin-l-top u-margin-xs-bottom\">Abstract<\/h2>\n<div id=\"abs0010\">\n<p id=\"sp0030\"><a class=\"topic-link\" title=\"Learn more about Ischemic stroke from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/brain-ischemia\">Ischemic stroke<\/a>\u00a0(IS) is one of the leading causes of death and disability. Its pathogenesis is not completely clear, and inflammatory cascade is one of its main\u00a0<a class=\"topic-link\" title=\"Learn more about pathological processes from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pathological-process\">pathological processes<\/a>. The current clinical practice of IS is to restore the\u00a0<a class=\"topic-link\" title=\"Learn more about blood supply from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vascularity\">blood supply<\/a>\u00a0to the ischemic area after IS as soon as possible through\u00a0<a class=\"topic-link\" title=\"Learn more about thrombolytic therapy from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/fibrinolytic-therapy\">thrombolytic therapy<\/a>\u00a0to protect the vitality and function of neurons. However, blood reperfusion further accelerates ischemic damage and cause ischemia-reperfusion injury. The pathological process of cerebral ischemia-reperfusion injury involves multiple mechanisms, and the exact mechanism has not been fully elucidated.\u00a0<a class=\"topic-link\" title=\"Learn more about Pyroptosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pyroptosis\">Pyroptosis<\/a>, a newly discovered form of inflammatory\u00a0<a class=\"topic-link\" title=\"Learn more about programmed cell death from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/programmed-cell-death\">programmed cell death<\/a>, plays an important role in the initiation and progression of inflammation. It is a pro-inflammatory programmed death mediated by\u00a0<a class=\"topic-link\" title=\"Learn more about caspase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/caspase\">caspase<\/a>\u00a0Caspase-1\/4\/5\/11, which can lead to cell swelling and rupture, release inflammatory factors IL-1\u03b2 and IL-18, and induce an inflammatory cascade. Recent studies have shown that pyroptosis and its mediated inflammatory response are important factors in aggravating ischemic brain injury, and inhibition of pyroptosis may alleviate the ischemic brain injury. Furthermore, studies have found that natural plant components may have a regulatory effect on pyroptosis. Therefore, this review not only summarizes the molecular mechanism of pyroptosis and its role in ischemic stroke, but also the role of natural plant components as regulator of pyroptosis, in order to provide reference information on pyroptosis for the\u00a0<a class=\"topic-link\" title=\"Learn more about treatment from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/therapeutic-procedure\">treatment<\/a>\u00a0of IS in the future.<\/p>\n<div class=\"Keywords u-font-serif text-s\">\n<div id=\"keys0005\" class=\"keywords-section\">\n<h2 class=\"section-title u-h4 u-margin-l-top u-margin-xs-bottom\">Keywords<\/h2>\n<div id=\"key0005\" class=\"keyword\">Pyroptosis; Ischemic stroke; Caspases; Natural plant components; Inflammasome<\/div>\n<\/div>\n<\/div>\n<div id=\"body\" class=\"Body u-font-serif text-s\">\n<div>\n<section id=\"sec0005\">\n<h2 id=\"sect0025\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">1.\u00a0Introduction<\/h2>\n<p id=\"p0025\">With the aging of the world&#8217;s population, the incidence of\u00a0<a class=\"topic-link\" title=\"Learn more about cerebrovascular disease from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cerebrovascular-disease\">cerebrovascular disease<\/a>\u00a0(such as stroke) has become the second largest in the world, and the threat to human beings is increasing\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib1\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib1\"><span class=\"anchor-text\">[1]<\/span><\/a>. Stroke includes\u00a0<a class=\"topic-link\" title=\"Learn more about ischemic stroke from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/brain-ischemia\">ischemic stroke<\/a>\u00a0(IS) and\u00a0<a class=\"topic-link\" title=\"Learn more about hemorrhagic stroke from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cerebral-hemorrhage\">hemorrhagic stroke<\/a>, and up to 87% of strokes are ischemic\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib2\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib2\"><span class=\"anchor-text\">[2]<\/span><\/a>. IS is a common clinical emergency, and its incidence is increasing year by year. The current clinical practice of IS is to restore the\u00a0<a class=\"topic-link\" title=\"Learn more about blood supply from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vascularity\">blood supply<\/a>\u00a0to the ischemic area after IS as soon as possible through\u00a0<a class=\"topic-link\" title=\"Learn more about thrombolytic therapy from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/fibrinolytic-therapy\">thrombolytic therapy<\/a>\u00a0to protect the vitality and function of neurons\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib3\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib3\"><span class=\"anchor-text\">[3]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib4\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib4\"><span class=\"anchor-text\">[4]<\/span><\/a>. However, ischemia-reperfusion injury (IRI) after restoration of blood flow often causes more serious damage to\u00a0<a class=\"topic-link\" title=\"Learn more about brain tissue from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-tissue\">brain tissue<\/a>\u00a0and nerve cells, which further becomes an important factor leading to poor prognosis and dysfunction of patients\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib5\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib5\"><span class=\"anchor-text\">[5]<\/span><\/a>. The worldwide epidemiological survey analyzed data from 1990 to 2019 in 204 countries and regions around the world. Their report states that stroke remains the second leading cause of death (11.6% of total deaths) and the third leading cause of death and disability [5.7% of total\u00a0<a class=\"topic-link\" title=\"Learn more about Disability adjusted life years from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/disability-adjusted-life-years\">Disability adjusted life years<\/a>\u00a0(DALYs)], which is second only to\u00a0<a class=\"topic-link\" title=\"Learn more about neonatal disease from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/newborn-disease\">neonatal disease<\/a>\u00a0(7.3% DALYs) and\u00a0<a class=\"topic-link\" title=\"Learn more about ischemic heart disease from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ischemic-heart-disease\">ischemic heart disease<\/a>\u00a0(7.2% DALYs), and the number of stroke patients is still increasing\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib6\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib6\"><span class=\"anchor-text\">[6]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib7\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib7\"><span class=\"anchor-text\">[7]<\/span><\/a>, especially in China. China has become the country with the highest risk of stroke in the world, with the risk of stroke among residents reaching 39.3%, and the risk of stroke among Chinese males is also the highest among males in the world, exceeding 41%; IS has risen from the third leading cause of death (as of 1990) to the first (as of 2017) among Chinese residents\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib8\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib8\"><span class=\"anchor-text\">[8]<\/span><\/a>. Current studies suggest that the pathological mechanisms of cerebral IRI (CIRI) are mainly\u00a0<a class=\"topic-link\" title=\"Learn more about oxidative stress from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/oxidative-stress\">oxidative stress<\/a>\u00a0injury,\u00a0<a class=\"topic-link\" title=\"Learn more about inflammatory injury from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/inflammatory-injury\">inflammatory injury<\/a>, mitochondrial injury, autophagy, and\u00a0<a class=\"topic-link\" title=\"Learn more about apoptosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/programmed-cell-death\">apoptosis<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib9\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib9\"><span class=\"anchor-text\">[9]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib10\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib10\"><span class=\"anchor-text\">[10]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib11\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib11\"><span class=\"anchor-text\">[11]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib12\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib12\"><span class=\"anchor-text\">[12]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib13\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib13\"><span class=\"anchor-text\">[13]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib14\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib14\"><span class=\"anchor-text\">[14]<\/span><\/a>. However, these are still insufficient to explain the pathological mechanism of\u00a0<a class=\"topic-link\" title=\"Learn more about CIRI from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/immunoreactive-insulin\">CIRI<\/a>. For example, neuronal death after CIRI is thought to be mainly caused by apoptosis, and the direction of neuronal cell protection is mainly anti-apoptosis. However, apoptosis is not directly related to inflammation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib15\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib15\"><span class=\"anchor-text\">[15]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib16\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib16\"><span class=\"anchor-text\">[16]<\/span><\/a>, but there is a substantial the inflammatory response in CIRI\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib16\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib16\"><span class=\"anchor-text\">[16]<\/span><\/a>. Therefore, it is necessary to further clarify the pathophysiological mechanism of IS and further explore the etiology of CIRI.<\/p>\n<p id=\"p0030\"><a class=\"topic-link\" title=\"Learn more about Pyroptosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pyroptosis\">Pyroptosis<\/a>, also known as\u00a0<a class=\"topic-link\" title=\"Learn more about cell inflammatory from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/inflammatory-cell\">cell inflammatory<\/a>\u00a0necrosis, is a newly discovered and confirmed programmed cell death in recent years\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib17\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib17\"><span class=\"anchor-text\">[17]<\/span><\/a>. Pyroptosis is dependent on inflammatory\u00a0<a class=\"topic-link\" title=\"Learn more about caspases from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/caspase\">caspases<\/a>\u00a0(mainly caspase-1, 4, 5, 11) and is accompanied by the release of a large number of pro-inflammatory factors. It is manifested by the continuous expansion of cells until the cell\u00a0<a class=\"topic-link\" title=\"Learn more about membrane ruptures from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/membrane-rupture\">membrane ruptures<\/a>, resulting in the release of the cellular contents and the activation of a strong inflammatory response\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib17\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib17\"><span class=\"anchor-text\">[17]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib18\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib18\"><span class=\"anchor-text\">[18]<\/span><\/a>. The\u00a0<a class=\"topic-link\" title=\"Learn more about morphological characteristics from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/morphological-trait\">morphological characteristics<\/a>, occurrence and regulatory mechanism of pyroptosis are different from other cell death methods such as apoptosis and necrosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib18\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib18\"><span class=\"anchor-text\">[18]<\/span><\/a>. Pyroptosis is widely involved in the occurrence and development of various diseases such as infectious diseases, nervous system-related diseases, atherosclerotic diseases and malignant tumors\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib19\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib19\"><span class=\"anchor-text\">[19]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib20\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib20\"><span class=\"anchor-text\">[20]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib21\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib21\"><span class=\"anchor-text\">[21]<\/span><\/a>. The latest studies show that pyroptosis and its mediated inflammatory response are involved in the\u00a0<a class=\"topic-link\" title=\"Learn more about pathological process from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pathological-process\">pathological process<\/a>\u00a0of IS, and preventing the activation of pyroptosis is beneficial to inhibiting the inflammatory cascade and reducing ischemic brain injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib22\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib22\"><span class=\"anchor-text\">[22]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib23\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib23\"><span class=\"anchor-text\">[23]<\/span><\/a>. Based on this, the study of pyroptosis is crucial for the\u00a0<a class=\"topic-link\" title=\"Learn more about treatment from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/therapeutic-procedure\">treatment<\/a>\u00a0of IS; regulating pyroptosis may reduce the fatality rate of IS, improve the survival rate of neurons, and improve the symptoms of IS patients. Currently,\u00a0<a class=\"topic-link\" title=\"Learn more about drugs from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/chemotherapeutic-agent\">drugs<\/a>\u00a0that exert\u00a0<a class=\"topic-link\" title=\"Learn more about neuroprotective from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neuroprotective-agent\">neuroprotective<\/a>\u00a0effects by regulating the pyroptosis pathway are being developed. In particular, there are many studies on natural plant components regulating the pyroptosis of vascular neuronal units in IS. Our previous studies also showed that\u00a0<a class=\"topic-link\" title=\"Learn more about saponins from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/saponin\">saponins<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib24\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib24\"><span class=\"anchor-text\">[24]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib25\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib25\"><span class=\"anchor-text\">[25]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib26\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib26\"><span class=\"anchor-text\">[26]<\/span><\/a>\u00a0and multicomponent compounds\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib27\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib27\"><span class=\"anchor-text\">[27]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib28\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib28\"><span class=\"anchor-text\">[28]<\/span><\/a>\u00a0can regulate the\u00a0<a class=\"topic-link\" title=\"Learn more about biological process from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/biological-phenomena-and-functions-concerning-the-entire-organism\">biological process<\/a>\u00a0of pyroptosis in IS. Therefore, this review not only summarizes the molecular mechanism of pyroptosis and its role in ischemic stroke, but also the role of natural plant components as regulator of pyroptosis so as to provide lead compounds or natural plant components for future pyroptosis-related drug development.<\/p>\n<\/section>\n<section id=\"sec0010\">\n<h2 id=\"sect0030\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">2.\u00a0Pyroptosis<\/h2>\n<section id=\"sec0015\">\n<h3 id=\"sect0035\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">2.1.\u00a0The characteristics of pyroptosis<\/h3>\n<div>\n<p id=\"p0035\"><a class=\"topic-link\" title=\"Learn more about Pyroptosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pyroptosis\">Pyroptosis<\/a>\u00a0is a form of\u00a0<a class=\"topic-link\" title=\"Learn more about programmed cell death from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/programmed-cell-death\">programmed cell death<\/a>\u00a0dependent on pro-inflammatory\u00a0<a class=\"topic-link\" title=\"Learn more about caspases from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/caspase\">caspases<\/a>, which is characterized by the formation of transmembrane pores, swelling and rupture of cell membranes, and the release of pro-inflammatory contents\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib29\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib29\"><span class=\"anchor-text\">[29]<\/span><\/a>. In the process of apoptosis, cells have nuclear fragmentation and cell membrane integrity, which does not cause inflammatory response in surrounding tissues, while cells in the process of pyroptosis have a complete nuclear morphology and cell\u00a0<a class=\"topic-link\" title=\"Learn more about membrane rupture from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/membrane-rupture\">membrane rupture<\/a>, which causes peripheral inflammation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib30\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib30\"><span class=\"anchor-text\">[30]<\/span><\/a>. When pyroptosis occurs, the cell membrane will gradually rupture to form 1\u20132\u00a0nm cell membrane pores, and then the cell contents such as intracellular inflammatory factors and other substances are released outside the cell membrane. Membrane-penetrating dyes such as\u00a0<a class=\"topic-link\" title=\"Learn more about ethidium bromide from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ethidium-bromide\">ethidium bromide<\/a>\u00a0can be used to observe whether cells undergo pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib31\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib31\"><span class=\"anchor-text\">[31]<\/span><\/a>. In addition, the occurrence of necrosis depends on the mixed series protein kinase-like\u00a0<a class=\"topic-link\" title=\"Learn more about domain protein from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/protein-domain\">domain protein<\/a>\u00a0(MLKL), which is selective for ions entering the cell, and the nuclear chromatin is flocculent or edge-clumped. Pyroptosis is dependent on the pore-forming protein GSDMD, a non-selective protein that causes nuclear\u00a0<a class=\"topic-link\" title=\"Learn more about pyknosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pyknosis\">pyknosis<\/a>\u00a0and\u00a0<a class=\"topic-link\" title=\"Learn more about DNA fragmentation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/dna-fragmentation\">DNA fragmentation<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib32\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib32\"><span class=\"anchor-text\">[32]<\/span><\/a>. There are similarities and differences among pyroptosis, apoptosis, necroptosis and\u00a0<a class=\"topic-link\" title=\"Learn more about ferroptosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ferroptosis\">ferroptosis<\/a>, such as the cause, cell changes, etc. The details are shown in\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#tbl0005\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"tbl0005\"><span class=\"anchor-text\">Table 1<\/span><\/a>.<\/p>\n<div id=\"tbl0005\" class=\"tables colsep-0 rowsep-0 frame-topbot\">\n<p id=\"sp0020\"><span class=\"label\">Table 1<\/span>.\u00a0Similarities and differences among pyroptosis, apoptosis and necroptosis.<\/p>\n<div class=\"groups\">\n<table>\n<thead>\n<tr class=\"rowsep-1\">\n<th scope=\"col\">Characteristics<\/th>\n<th scope=\"col\">Signature components<\/th>\n<th scope=\"col\">Changes in cells<\/th>\n<th scope=\"col\">General cause<\/th>\n<th scope=\"col\">Inhibitors<\/th>\n<th scope=\"col\">Reference<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<th scope=\"row\">Pyroptosis<\/th>\n<td>Pyroptosome, inflammasome<\/td>\n<td>Pore formation, cell swelling, plasma membrane rupture, chromatin condensation, DNA fragmentation but nuclear integrity, etc.<\/td>\n<td>DAMP, PAMP, infection<\/td>\n<td>GSDMD inhibitors<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib19\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib19\"><span class=\"anchor-text\">[19]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib33\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib33\"><span class=\"anchor-text\">[33]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib34\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib34\"><span class=\"anchor-text\">[34]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib35\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib35\"><span class=\"anchor-text\">[35]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib36\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib36\"><span class=\"anchor-text\">[36]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Apoptosis<\/th>\n<td>Apoptosome<\/td>\n<td>Cell shrinks with intact membrane, plasma membrane blebbing, chromatin condensation, DNA fragmentation, etc.<\/td>\n<td>Gene regulation of physiological states<\/td>\n<td>Regulating caspase family, Bcl-2 family, p53, etc.<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib37\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib37\"><span class=\"anchor-text\">[37]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib38\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib38\"><span class=\"anchor-text\">[38]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib39\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib39\"><span class=\"anchor-text\">[39]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Necroptosis<\/th>\n<td>Necrosome<\/td>\n<td>Cell swelling, plasma membrane rupture, organelle swelling, chromatin condensation, etc.<\/td>\n<td>Serious injury<\/td>\n<td>Nec-1, NSA, etc.<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib33\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib33\"><span class=\"anchor-text\">[33]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib40\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib40\"><span class=\"anchor-text\">[40]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib41\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib41\"><span class=\"anchor-text\">[41]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib42\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib42\"><span class=\"anchor-text\">[42]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib43\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib43\"><span class=\"anchor-text\">[43]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Ferroptosis<\/th>\n<td>NRF2, GPX4, ACSL4, etc.<\/td>\n<td>Occurs mainly in mitochondria, with reduced mitochondrial cristae, condensed membranes, and ruptured outer membranes.<\/td>\n<td>Fe2\u00a0+\u00a0overload and ROS<\/td>\n<td>GSH, deferoxamine, liproxstatin-1, ferrostatin-1, etc.<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib44\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib44\"><span class=\"anchor-text\">[44]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib45\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib45\"><span class=\"anchor-text\">[45]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib46\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib46\"><span class=\"anchor-text\">[46]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib47\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib47\"><span class=\"anchor-text\">[47]<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n<section id=\"sec0020\">\n<h3 id=\"sect0040\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">2.2.\u00a0The molecular mechanism of pyroptosis<\/h3>\n<p id=\"p0040\">The formation of\u00a0<a class=\"topic-link\" title=\"Learn more about inflammasome from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/inflammasome\">inflammasome<\/a>\u00a0is the key substance for pyroptosis after injury. When injured, the body can activate the pattern signal related to pathogen-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs)\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib48\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib48\"><span class=\"anchor-text\">[48]<\/span><\/a>. When signal stimulation occurs, the intracellular\u00a0<a class=\"topic-link\" title=\"Learn more about promoter protein from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/promoter-protein\">promoter protein<\/a>\u00a0nucleotide-binding oligomerization domain-like receptor\u00a0<a class=\"topic-link\" title=\"Learn more about pyrin domain from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pyrin-domain\">pyrin domain<\/a>\u00a0containing 3 (NLRP3) can recruit a large amount of procaspase-1 using the inflammasome adaptor molecule ASC through oligomerization\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib49\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib49\"><span class=\"anchor-text\">[49]<\/span><\/a>, the formation of inflammasome aggregated proteins. Procaspase-1 is the precursor of caspase-1, and normally procaspase-1 exists in the body in the form of\u00a0<a class=\"topic-link\" title=\"Learn more about zymogen from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/enzyme-precursor\">zymogen<\/a>. When stimulatory signals are delivered to procaspase-1, it generates P20 and P10 subunits by autohydrolysis. This subunit first forms a\u00a0<a class=\"topic-link\" title=\"Learn more about heterodimer from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/heterodimer\">heterodimer<\/a>\u00a0that cannot function, and then aggregates to form a\u00a0<a class=\"topic-link\" title=\"Learn more about tetramer from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/tetramer\">tetramer<\/a>\u00a0that promotes caspase-1 activity, leading to caspase-1 activation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib50\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib50\"><span class=\"anchor-text\">[50]<\/span><\/a>. When caspase-1 is activated, the active caspase-1 is responsible for the formation of cell membrane pores and rapid lysis of the cell membrane to form an inflammatory response. Meanwhile, caspase-1 can also induce the precursors of IL-1\u03b2 and IL-18, pro-IL-1\u03b2 and pro-IL-18, to accelerate the maturation process. The mature IL-1\u03b2 and IL-18 are released extracellularly, thereby recruiting more inflammasomes. After the inflammasome aggregates, the inflammatory response is further aggravated, and the tissue damage is aggravated. After IL-1\u03b2 is released from cells, inflammatory factors spread to adjacent tissues along with the flow of lymph, further aggravating the inflammatory response. The secretion of a large amount of IL-18 causes Th1 and Th2 immune responses, and stimulates the immune response to play a role\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib51\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib51\"><span class=\"anchor-text\">[51]<\/span><\/a>.<\/p>\n<section id=\"sec0025\">\n<h4 id=\"sect0045\" class=\"u-margin-m-top u-margin-xs-bottom\">2.2.1.\u00a0Canonical pyroptosis pathway<\/h4>\n<p id=\"p0045\">Caspase-1 is a key protein in the canonical pyroptotic pathway, in which the inflammasome plays an important role in the activation of Caspase-1\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib52\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib52\"><span class=\"anchor-text\">[52]<\/span><\/a>. The inflammasome is an important part of the innate immune system and is a multi-protein complex composed of sensor proteins, ASC and pro-Caspase-1. It exists in the cytoplasm of stimulated\u00a0<a class=\"topic-link\" title=\"Learn more about immune cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/immunocompetent-cell\">immune cells<\/a>\u00a0and can sense extracellular stimulatory signals\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib53\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib53\"><span class=\"anchor-text\">[53]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib54\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib54\"><span class=\"anchor-text\">[54]<\/span><\/a>. Inflammasomes are divided into inflammasomes containing nucleotide-binding oligomerization domain-like receptors (NLRs), abstract in\u00a0<a class=\"topic-link\" title=\"Learn more about melanoma from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nodular-melanoma\">melanoma<\/a>\u00a02 (AIM2) inflammasomes and NLRC4 inflammasomes\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib55\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib55\"><span class=\"anchor-text\">[55]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib56\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib56\"><span class=\"anchor-text\">[56]<\/span><\/a>. Purinergic 2\u00a0\u00d7\u00a07 (P2X7) receptor is an ATP-gated transmembrane ion channel receptor expressed in\u00a0<a class=\"topic-link\" title=\"Learn more about microglia from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/microglia\">microglia<\/a>\u00a0and is a key factor in inflammasome activation. Studies have shown that extracellular ATP can regulate K+\u00a0efflux by activating the\u00a0<a class=\"topic-link\" title=\"Learn more about P2X7 receptor from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/purinergic-p2x7-receptor\">P2X7 receptor<\/a>, inducing the activation of the NLR family, pyrin domain-containing 3 (NLRP3)\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib57\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib57\"><span class=\"anchor-text\">[57]<\/span><\/a>. The NLRP3 inflammasome is currently the most studied. Activation of the NLRP3 inflammasome requires a two-step response: initiation of the response, microbial or endogenous factor nuclear factor-\u03baB (NF-\u03baB) into the nucleus, and upregulation of NLRP3 and pro-IL-1\u03b2 expression\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib58\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib58\"><span class=\"anchor-text\">[58]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib59\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib59\"><span class=\"anchor-text\">[59]<\/span><\/a>. When immune cells are stimulated by DAMPs, the sensor protein recruits pro-Caspase-1 through the ASC, which is then activated by autohydrolysis. Mature Caspase-1 processes downstream inactive pro-IL-1\u03b2 and pro-IL-18 into active IL-1\u03b2 and IL-18\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib60\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib60\"><span class=\"anchor-text\">[60]<\/span><\/a>. Meanwhile, Caspase-1 cleaves the downstream GSDMD protein into GSDMD-N fragment and GSDMD-C fragment with pore-forming activity. The GSDMD-N fragment specifically recognizes and binds to the\u00a0<a class=\"topic-link\" title=\"Learn more about membrane lipids from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/membrane-lipid\">membrane lipids<\/a>\u00a0on the inner side of the cell membrane, causing changes in intracellular and extracellular osmotic pressure, which in turn leads to cell swelling and rupture and the release of inflammatory factors IL-1\u03b2 and IL-18, inducing inflammatory response and cell pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib61\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib61\"><span class=\"anchor-text\">[61]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0030\">\n<h4 id=\"sect0050\" class=\"u-margin-m-top u-margin-xs-bottom\">2.2.2.\u00a0Non-canonical pyroptosis pathway<\/h4>\n<p id=\"p0050\">Caspase family is mainly divided into two categories: apoptosis-related and inflammation-related according to different functions. Caspase-3\/2\/10 mainly mediate apoptosis, while caspase-1\/4\/5\/11 are key mediators of inflammation and innate immune responses\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib62\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib62\"><span class=\"anchor-text\">[62]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib63\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib63\"><span class=\"anchor-text\">[63]<\/span><\/a>. The non-canonical pyroptotic pathway is dependent on Caspase-4\/5\/11 activation, whereas the inflammasome is not essential for the maturation of IL-1\u03b2 and IL-18\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib64\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib64\"><span class=\"anchor-text\">[64]<\/span><\/a>. The non-classical pathway of pyroptosis is induced by\u00a0<a class=\"topic-link\" title=\"Learn more about lipopolysaccharide from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/lipopolysaccharide\">lipopolysaccharide<\/a>\u00a0(LPS), a cell wall component of Gram-negative bacteria. LPS can directly bind to human Caspase-4\/5 and mouse Caspase-11. These caspases act as both sensor proteins and effector molecules of LPS. The activated Caspase-4\/5\/11 directly cleave GSDMD and induce pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib65\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib65\"><span class=\"anchor-text\">[65]<\/span><\/a>. In addition, studies have found that Caspase-11 can activate the downstream\u00a0<a class=\"topic-link\" title=\"Learn more about gap junction from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/gap-junction\">gap junction<\/a>\u00a0<a class=\"topic-link\" title=\"Learn more about channel protein from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/channel-protein\">channel protein<\/a>\u00a0Pannexin-1 to promote K+\u00a0efflux, and K+\u00a0efflux can activate the NLRP3 inflammasome, which in turn activates Caspase-1 and promotes the maturation of IL-1\u03b2 and IL-18\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib66\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib66\"><span class=\"anchor-text\">[66]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0035\">\n<h4 id=\"sect0055\" class=\"u-margin-m-top u-margin-xs-bottom\">2.2.3.\u00a0The relationship between GSDMD and pyroptosis<\/h4>\n<p id=\"p0055\">GSDMD (Gsdermin D) is a protein composed of 484 amino acid residue fragments and is a member of the Gasdermin protein family. There are mainly 5 members in this family, they are: DFNA5, DFNB59, GSDMA, GSDMB, GSDMCD. The amino acid structures of these five proteins are highly similar, and these proteins contain two spatial domains, N-terminal and C-terminal\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib67\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib67\"><span class=\"anchor-text\">[67]<\/span><\/a>. GSDMD protein is a long-chain amino\u00a0<a class=\"topic-link\" title=\"Learn more about acid protein from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/acid-protein\">acid protein<\/a>, and the structure between its N-terminal and C-terminal domains is relatively loose. GSDMD is typically cleaved at\u00a0<a class=\"topic-link\" title=\"Learn more about amino acid sequence from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/peptide-sequence\">amino acid sequence<\/a>\u00a0275, exposing the N-terminal and C-terminal domains. In\u00a0<a class=\"topic-link\" title=\"Learn more about mammalian cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mammalian-cell\">mammalian cells<\/a>, the simple N-terminal structure of GSDMD can regulate cell pyroptosis. Therefore, GSDMD often expresses the N-terminal domain but cannot express all GSDMD proteins\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib68\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib68\"><span class=\"anchor-text\">[68]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib69\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib69\"><span class=\"anchor-text\">[69]<\/span><\/a>. However, studies have shown that when the N-terminal domain of GSDMD was introduced into E. coli for culture, strong toxic effects occurred. In contrast, intact GSDMD and the C-terminal domain of GSDMD showed relatively low toxicity\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib70\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib70\"><span class=\"anchor-text\">[70]<\/span><\/a>. The N-terminal structure of intracellular GSDMD will gradually transfer to the cell membrane with the invasion of damage factors, and on the cell membrane, where it specifically binds to phosphosarcosinase and\u00a0<a class=\"topic-link\" title=\"Learn more about phosphatidylserine from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/phosphatidylserine\">phosphatidylserine<\/a>\u00a0on the cell membrane to produce biological effects\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib71\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib71\"><span class=\"anchor-text\">[71]<\/span><\/a>. Using equipment such as atomic force\u00a0<a class=\"topic-link\" title=\"Learn more about electron microscopy from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/electron-microscopy\">electron microscopy<\/a>\u00a0and cryo-electron microscopy, L. Sborigi observed that the N-terminal structure of GSDMD can be combined with biofilms to form a hollow ring-like polymer on the biofilm. This polymer induces the formation of biofilm pores, due to which GSDMD induces pyroptosis in cells when endogenous damage occurs. When external\u00a0<a class=\"topic-link\" title=\"Learn more about pathogens from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pathogen\">pathogens<\/a>\u00a0invade, they are able to adsorb on the cell surface of pathogens and protect the body from external harmful substances by lysing the cells\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib72\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib72\"><span class=\"anchor-text\">[72]<\/span><\/a>. GSDMD is a substance that specifically binds to caspase-1\/4\/5\/11 proteins downstream of\u00a0<a class=\"topic-link\" title=\"Learn more about signal transduction from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/signal-transduction\">signal transduction<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib73\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib73\"><span class=\"anchor-text\">[73]<\/span><\/a>. Caspase-1 promotes the release of downstream IL-1\u03b2 and IL-18 out of the cell membrane through inflammasome responses generated by complexes with various proteins. Activated caspase-1 cleaves GSDMD protein, converting GSDMD into active peptides. The decomposition products of GSDMD specifically bind to the cell membrane, and components such as extracellular water molecules enter the cell membrane through the pores, causing the cells to swell and eventually rupture\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib74\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib74\"><span class=\"anchor-text\">[74]<\/span><\/a>.<\/p>\n<\/section>\n<\/section>\n<section id=\"sec0040\">\n<h3 id=\"sect0060\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">2.3.\u00a0Noncoding RNAs participate in the expression of pyroptotic genes in IS<\/h3>\n<p id=\"p0060\">In recent years, the regulatory mechanism at the gene level related to the occurrence of pyroptosis has also been fully developed. Modern molecular biology studies show that 98% of the genome is not involved in coding proteins. Long-chain coding RNAs (lncRNAs) are RNAs with no protein-coding function, so named because they are more than 200 nucleotides in length\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib75\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib75\"><span class=\"anchor-text\">[75]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib76\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib76\"><span class=\"anchor-text\">[76]<\/span><\/a>. However, although\u00a0<a class=\"topic-link\" title=\"Learn more about lncRNA from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/long-untranslated-rna\">lncRNA<\/a>\u00a0does not have the function of encoding protein, it is the most expressed gene in the body and the most conserved gene in transcription. It participates in important pathological and physiological processes in the body, especially in reperfusion injury-related diseases, and plays an important role\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib77\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib77\"><span class=\"anchor-text\">[77]<\/span><\/a>. Studies have shown that in microglia, the expression level of lncRNA-H19 is positively correlated with the duration of reperfusion\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib78\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib78\"><span class=\"anchor-text\">[78]<\/span><\/a>. Overexpression of LncRNA-H19 plays an inflammatory role when it promotes the expression of the downstream signaling molecule NLRP3\/6 and initiates GSDMD\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib79\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib79\"><span class=\"anchor-text\">[79]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib80\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib80\"><span class=\"anchor-text\">[80]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib81\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib81\"><span class=\"anchor-text\">[81]<\/span><\/a>. lncRNA-H19 is able to activate members of the caspase protein family\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib82\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib82\"><span class=\"anchor-text\">[82]<\/span><\/a>, leading to mitochondrial dysfunction, participating in the activation of inflammasomes, and causing neuronal damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib83\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib83\"><span class=\"anchor-text\">[83]<\/span><\/a>. In addition to the regulation of molecular structure, lncRNA-H19 can also recruit more transcription factors to regulate the mRNA transcription process\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib84\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib84\"><span class=\"anchor-text\">[84]<\/span><\/a>. In addition, lncRNA-H19 can also promote the\u00a0<a class=\"topic-link\" title=\"Learn more about nuclear transport from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nucleocytoplasmic-transport\">nuclear transport<\/a>\u00a0process of transcription factors, thereby increasing the specific expression of more target genes, and generating an inflammatory cascade network when\u00a0<a class=\"topic-link\" title=\"Learn more about ischemia from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ischemia\">ischemia<\/a>\u00a0occurs\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib84\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib84\"><span class=\"anchor-text\">[84]<\/span><\/a>. Therefore, lncRNA-H19 is a strong danger signal when\u00a0<a class=\"topic-link\" title=\"Learn more about CIRI from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/immunoreactive-insulin\">CIRI<\/a>\u00a0occurs, and inhibition of H19 may be a potential\u00a0<a class=\"topic-link\" title=\"Learn more about treatment from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/therapeutic-procedure\">treatment<\/a>\u00a0for ischemia-reperfusion injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib84\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib84\"><span class=\"anchor-text\">[84]<\/span><\/a>. In AIM2 inflammasome-mediated pyroptosis capable of ischemia-reperfusion injury, the lincRNA MEG3\/miR-485\/AIM2 axis promotes pyroptosis by activating caspase1 signaling during CIRI, and thus this axis may be an effective therapeutic target for\u00a0<a class=\"topic-link\" title=\"Learn more about IS from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/brain-ischemia\">IS<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib84\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib84\"><span class=\"anchor-text\">[84]<\/span><\/a>. For the\u00a0<a class=\"topic-link\" title=\"Learn more about immune regulation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/immunoregulation\">immune regulation<\/a>\u00a0of microglia, Wang et al. found that LncRNA-Fendrr protects the\u00a0<a class=\"topic-link\" title=\"Learn more about ubiquitination from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ubiquitination\">ubiquitination<\/a>\u00a0and degradation of NLRC4 protein through HERC2 and regulates microglial pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib85\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib85\"><span class=\"anchor-text\">[85]<\/span><\/a>. Zhang et al. found that the lncRNA NEAT1\/miR-22\u20133p axis inhibited pyroptosis and attenuated CIRI injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib86\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib86\"><span class=\"anchor-text\">[86]<\/span><\/a>. In vitro oxygen-glucose deprivation (OGD) injury experiments after IS showed that OGD increased NOD-like receptor protein 3 (NLRP3) expression to induce pyroptotic death of NSCs, which was rescued by\u00a0<a class=\"topic-link\" title=\"Learn more about hyperbaric oxygen therapy from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/hyperbaric-medicine\">hyperbaric oxygen therapy<\/a>. The upregulated lncRNA-H19 acts as a molecular sponge for miR-423\u20135p, targeting NLRP3 after OGD to induce neural stem cell (NSC) pyroptosis. Therefore, it was confirmed that hyperbaric oxygen therapy protects NSCs from pyroptosis by inhibiting the lncRNA-H19\/miR-423\u20135p\/NLRP3 axis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib87\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib87\"><span class=\"anchor-text\">[87]<\/span><\/a>. miR-21 is a\u00a0<a class=\"topic-link\" title=\"Learn more about microRNA from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/microrna\">microRNA<\/a>\u00a0(miRNA) that is closely related to the occurrence of pyroptosis. Studies have shown that miR-21 can specifically regulate NLRP3 protein, activate NLRP3 protein, stimulate NLRP3 secretion, and express in macrophages through NF-\u03baB signaling through the inflammatory feedback pathway\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib88\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib88\"><span class=\"anchor-text\">[88]<\/span><\/a>. In addition to activating NLRP3, miR-21 can also regulate the activation of downstream caspase-1, promote the secretion of IL-1\u03b2, and promote the occurrence of pyroptosis. When miR-21 is deficient, the expression of caspase-1 pathway regulated by NLRP3 is significantly reduced. Therefore, the expression level of miR-21 is also a key link in regulating the occurrence of pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib89\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib89\"><span class=\"anchor-text\">[89]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib90\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib90\"><span class=\"anchor-text\">[90]<\/span><\/a>. Modern molecular biology studies have shown that miR-214\u20133p has a binding site for caspase-1, which can specifically bind to the occurrence of caspase-1, thereby regulating the inflammatory response and increasing the incidence of pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib91\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib91\"><span class=\"anchor-text\">[91]<\/span><\/a>.<\/p>\n<div>\n<p id=\"p0065\">The molecular mechanism of pyroptosis was summarized in\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#fig0005\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"fig0005\"><span class=\"anchor-text\">Fig. 1<\/span><\/a>.<\/p>\n<figure id=\"fig0005\" class=\"figure text-xs\"><img decoding=\"async\" src=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr1.jpg\" alt=\"Fig. 1\" height=\"414\" aria-describedby=\"cap0005\" \/><\/p>\n<ol class=\"u-margin-s-bottom\">\n<li><a class=\"anchor download-link u-font-sans u-display-inline anchor-default\" title=\"Download high-res image (294KB)\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr1_lrg.jpg\" target=\"_blank\" rel=\"noopener\" download=\"\"><span class=\"anchor-text\">Download :\u00a0<span class=\"download-link-title\">Download high-res image (294KB)<\/span><\/span><\/a><\/li>\n<li><a class=\"anchor download-link u-font-sans u-display-inline anchor-default\" title=\"Download full-size image\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr1.jpg\" target=\"_blank\" rel=\"noopener\" download=\"\"><span class=\"anchor-text\">Download :\u00a0<span class=\"download-link-title\">Download full-size image<\/span><\/span><\/a><\/li>\n<\/ol>\n<p id=\"sp0005\"><span class=\"label\">Fig. 1<\/span>.\u00a0The molecular mechanism of pyroptosis (The mechanisms of pyroptosis include the canonical inflammasome pathway and the non-canonical inflammasome pathway. The canonical inflammasome pathway is triggered by DAMPs or PAMPs. The non-canonical inflammasome pathway is triggered by LPS of extracellular Gram-negative bacteria or death stimulation. After triggering, pyroptosis is triggered through a series of intermolecular interactions.\u00a0<a class=\"topic-link\" title=\"Learn more about TLR from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/toll-like-receptor\">TLR<\/a>: Toll-like receptor; GSDM: Gsdermin; NLRP3: nucleotide-binding oligomerization domain-like receptor\u00a0<a class=\"topic-link\" title=\"Learn more about pyrin domain from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pyrin-domain\">pyrin domain<\/a>\u00a0containing 3; DAMP: damage associated molecular pattern; PAMP: pathogen-associated molecular pattern).<\/p>\n<\/figure>\n<\/div>\n<\/section>\n<section id=\"sec0045\">\n<h3 id=\"sect0065\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">2.4.\u00a0The relationship between pyroptosis and other cellular damage<\/h3>\n<p id=\"p0070\">There are many mechanisms involved in the occurrence of cerebral ischemia-reperfusion injury. The known mechanisms are related to various mechanisms such as inflammatory response, calcium channel disorder, mitochondrial function impairment, and autophagy. Pyroptosis is involved in all aspects of cerebral ischemia-reperfusion injury and is closely related to other injuries.<\/p>\n<p id=\"p0075\">The occurrence of pyroptosis and apoptosis both belong to a way of cell death, but they are fundamentally different. Apoptosis is a physiological way of cell death, while pyroptosis is often associated with pathological cell death after body injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib92\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib92\"><span class=\"anchor-text\">[92]<\/span><\/a>. Autophagy is a kind of autophagy phenomenon that widely exists in\u00a0<a class=\"topic-link\" title=\"Learn more about eukaryotic cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/eukaryotic-cell\">eukaryotic cells<\/a>. Autophagy is generally divided into three types, namely chaperone-mediated autophagy, microautophagy, and macroautophagy. At present, there are many studies on macroautophagy\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib93\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib93\"><span class=\"anchor-text\">[93]<\/span><\/a>. Autophagy is an indispensable part of the normal metabolic process of cells. Inhibition of autophagy can lead to the accumulation of harmful substances in tissues, organs or cells. Excessive activation of autophagy will destroy important intracellular organelles and essential proteins, triggering autophagic apoptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib94\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib94\"><span class=\"anchor-text\">[94]<\/span><\/a>.<\/p>\n<p id=\"p0080\">Pyroptosis and autophagy are inextricably linked. Under normal circumstances, the occurrence of autophagy and pyroptosis in vivo is in a state of dynamic equilibrium. When the body mounts an inflammatory response to external stimuli, the balance between autophagy and pyroptosis is disrupted\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib95\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib95\"><span class=\"anchor-text\">[95]<\/span><\/a>. For example, NF-\u03baB is a\u00a0<a class=\"topic-link\" title=\"Learn more about signal transduction pathway from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/signal-transduction-pathway\">signal transduction pathway<\/a>\u00a0that participates in the signal transduction of many\u00a0<a class=\"topic-link\" title=\"Learn more about signal pathways from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cell-signaling-pathway\">signal pathways<\/a>\u00a0to achieve signal transduction. The study found that in IS mice with knockout of the NF-\u03baB gene,\u00a0<a class=\"topic-link\" title=\"Learn more about mTOR from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mammalian-target-of-rapamycin\">mTOR<\/a>\u00a0activity was inhibited and autophagy levels were enhanced. The signaling activation pathway of NF-\u03baB is a large number of stimuli to activate NF-\u03baB-induced kinases, which activate I\u03baK\u03b1, I\u03baKB and I\u03baK\u03b3 trimers, resulting in the phosphorylation and degradation of I\u03baB, and finally activate the NF-\u03baB signaling pathway. After activation, NF-\u03baB enters the cell and specifically binds to its corresponding DNA receptor, thereby stimulating the transcription of inflammatory factors and promoting the massive expression of inflammatory factors TNF-\u03b1, IL-1\u03b2 and IL-6. Studies have shown that the NF-\u03baB signaling pathway is involved in regulating the activation of the pre- and post-transcriptional levels of the key pyroptotic protein NLRP3 to induce pyroptosis. The abundantly expressed inflammatory factors may induce an inflammatory cascade in the body, induce pyroptosis, and further expand the inflammatory response, thereby aggravating brain damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib96\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib96\"><span class=\"anchor-text\">[96]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib97\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib97\"><span class=\"anchor-text\">[97]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib98\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib98\"><span class=\"anchor-text\">[98]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0050\">\n<h3 id=\"sect0070\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">2.5.\u00a0Mechanisms of pyroptosis and inflammation involved in IS<\/h3>\n<p id=\"p0085\">Inflammatory cascades exist in various stages of IS\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib99\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib99\"><span class=\"anchor-text\">[99]<\/span><\/a>. In the early stages of IS, blood flow in the brain slows and\u00a0<a class=\"topic-link\" title=\"Learn more about neutrophils from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neutrophil\">neutrophils<\/a>\u00a0adhere to the\u00a0<a class=\"topic-link\" title=\"Learn more about endothelial cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/endothelial-cell\">endothelial cells<\/a>\u00a0of ischemic vessels, and an initial acute inflammatory response begins\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib100\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib100\"><span class=\"anchor-text\">[100]<\/span><\/a>. With the occurrence of reperfusion after cerebral ischemia, exogenous inflammatory factors, inflammatory cells and inflammatory factors pass through the blood-brain barrier, resulting in the secondary effect of ischemia after reperfusion, and leading to the release of a large number of oxidation factors and\u00a0<a class=\"topic-link\" title=\"Learn more about free radicals from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/radical-chemistry\">free radicals<\/a>. At this time, the microglia in the\u00a0<a class=\"topic-link\" title=\"Learn more about brain tissue from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-tissue\">brain tissue<\/a>\u00a0are gradually activated in large quantities and produce more\u00a0<a class=\"topic-link\" title=\"Learn more about inflammatory mediators from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/inflammatory-mediator\">inflammatory mediators<\/a>. This type of inflammatory mediators can over-activate endothelial cells in the brain tissue and produce a large amount of\u00a0<a class=\"topic-link\" title=\"Learn more about tissue factor from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/thromboplastin\">tissue factor<\/a>\u00a0to accumulate the toxicity of amino acids. This further aggravates the release of oxidative factors, free radicals and\u00a0<a class=\"topic-link\" title=\"Learn more about carbon monoxide from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/carbon-monoxide\">carbon monoxide<\/a>, and activates inflammatory response-related signaling pathways such as NF-\u03baB, Toll-like receptors, and Nod-like receptors (NLRs)\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib101\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib101\"><span class=\"anchor-text\">[101]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib102\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib102\"><span class=\"anchor-text\">[102]<\/span><\/a>. For example, NLRs, studies have shown that there are 23 family members of NLRs, which are mainly expressed in the cell cytoplasm and play a key role in the innate immune response of the body. Members of the NLR family, Nalp1, Nalp3, Nalp5, and Ipaf, are able to activate caspase-1 activation through the\u00a0<a class=\"topic-link\" title=\"Learn more about adaptor protein from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/adaptor-protein\">adaptor protein<\/a>\u00a0ASC, initiate a cascade of inflammatory responses, and mediate pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib103\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib103\"><span class=\"anchor-text\">[103]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib104\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib104\"><span class=\"anchor-text\">[104]<\/span><\/a>. NLRP3 is an important component of inflammatory factors. NLRP3 contains three domains: PYD, NACHT, and LRR, which can be represented by LRR-NACHT-PYD: PYD-CARD: CARD-CARDC a spase domain. It responds to various signals of endogenous damage, so the activation of the NLRP3 inflammasome is considered to be the main type of pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib105\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib105\"><span class=\"anchor-text\">[105]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib106\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib106\"><span class=\"anchor-text\">[106]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib107\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib107\"><span class=\"anchor-text\">[107]<\/span><\/a>.<\/p>\n<p id=\"p0090\">Inflammasomes are protein complexes assembled after the body receives signals of infection or cell damage, and serve as a platform for the recruitment and activation of pro-caspase-1. The promoter protein NLRP3 can recruit large amounts of procaspase-1 through oligomerization using the inflammasome adaptor molecule ASC\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib108\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib108\"><span class=\"anchor-text\">[108]<\/span><\/a>. Procaspase-1 is the precursor of caspase-1, and active caspase-1 is responsible for rapidly lysing cells to activate and release extracellular IL-1\u03b2 and IL-18, which further aggravates the inflammatory response. Therefore, the occurrence of pyroptosis is closely related to the appearance of inflammatory response and the formation of inflammasomes. The occurrence of cerebral ischemia-reperfusion injury is more closely related to the interaction between pyroptosis and inflammatory response\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib109\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib109\"><span class=\"anchor-text\">[109]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib110\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib110\"><span class=\"anchor-text\">[110]<\/span><\/a>. Especially in the central nerve system, astrocytes induce the activation and proliferation of microglia and produce a large number of inflammatory mediators. These inflammatory mediators can activate endothelial cells to produce a variety of tissue factors, increase the toxicity of\u00a0<a class=\"topic-link\" title=\"Learn more about excitatory amino acids from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/excitatory-amino-acid\">excitatory amino acids<\/a>, and promote the release of\u00a0<a class=\"topic-link\" title=\"Learn more about nitric oxide from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nitric-oxide\">nitric oxide<\/a>\u00a0and oxygen free radicals. The above substances further lead to the activation of multiple inflammatory signal transduction pathways such as NF-\u03baB and JNK2\/STAT3, and promote the assembly of inflammasomes such as NLRP1 and NLRP3. Activated caspase-1 induces pyroptosis of cells, expands the inflammatory response, and aggravates cerebral ischemia-reperfusion injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib111\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib111\"><span class=\"anchor-text\">[111]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib112\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib112\"><span class=\"anchor-text\">[112]<\/span><\/a>. Some studies have found that compared with wild-type mice, the levels of AIM2 and IL-1\u03b2 in the brain of AIM2\u00a0<a class=\"topic-link\" title=\"Learn more about knockout mice from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/knockout-mouse\">knockout mice<\/a>\u00a0after cerebral ischemia-reperfusion were significantly decreased, the infarct volume was significantly reduced, and the\u00a0<a class=\"topic-link\" title=\"Learn more about neurological function from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nervous-system-physiology\">neurological function<\/a>\u00a0scores were also significantly improved. Inhibition of AIM2 inflammasome activation can inhibit the occurrence of pyroptosis to a certain extent, thereby reducing ischemic brain injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib113\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib113\"><span class=\"anchor-text\">[113]<\/span><\/a>. Therefore, pyroptosis plays an important role in the process of cerebral ischemia-reperfusion injury. The NLRP3 inflammasome is a key protein in the pyroptotic pathway, and inhibiting its expression can simultaneously inhibit the expression of downstream pyroptotic pathway-related proteins, limit the inflammatory response and alleviate cerebral ischemia-reperfusion injury.<\/p>\n<\/section>\n<section id=\"sec0055\">\n<h3 id=\"sect0075\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">2.6.\u00a0Pyroptosis and mitochondrial damage mediate oxidative stress injury after IS<\/h3>\n<p id=\"p0095\">Mitochondria are mainly involved in the aerobic respiration of cells and are the place where aerobic respiration occurs. Mitochondria provides an ionized basis for normal signal transmission between cells and signal transduction of nerve cells\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib114\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib114\"><span class=\"anchor-text\">[114]<\/span><\/a>. Mitochondrial damage is mostly caused by abnormal\u00a0<a class=\"topic-link\" title=\"Learn more about mitochondrial metabolism from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mitochondrial-respiration\">mitochondrial metabolism<\/a>\u00a0and oxidative damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib115\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib115\"><span class=\"anchor-text\">[115]<\/span><\/a>. Studies have shown that cerebral ischemia-reperfusion injury is closely related to mitochondrial dysfunction\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib116\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib116\"><span class=\"anchor-text\">[116]<\/span><\/a>. Oxidative stress, as the key to the occurrence of oxidative damage, is closely related to pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib117\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib117\"><span class=\"anchor-text\">[117]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib118\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib118\"><span class=\"anchor-text\">[118]<\/span><\/a>. Oxidative stress is more likely to be expressed in brain tissue injury, especially in cerebral ischemia and\u00a0<a class=\"topic-link\" title=\"Learn more about reperfusion injury from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/reperfusion-injury\">reperfusion injury<\/a>\u00a0after cerebral ischemia\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib119\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib119\"><span class=\"anchor-text\">[119]<\/span><\/a>. When the body is attacked by external harmful substances, the cells can secrete a large amount of\u00a0<a class=\"topic-link\" title=\"Learn more about ROS from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/reactive-oxygen-species\">ROS<\/a>\u00a0and\u00a0<a class=\"topic-link\" title=\"Learn more about activated carbon from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/activated-charcoal\">activated carbon<\/a>, which disrupts the balance between oxidation and anti-oxidation, resulting in a series of oxidative damage reactions\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib120\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib120\"><span class=\"anchor-text\">[120]<\/span><\/a>. Most of ROS are secreted by mitochondria\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib121\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib121\"><span class=\"anchor-text\">[121]<\/span><\/a>. When stimulated by external stimuli or endogenous damage occurs, the body stimulates the binding of nucleotides to NLRP3 by inducing high levels of ROS, activating the inflammasome protein complex. When ROS is overactivated, the normal order of signaling pathways in the body is disrupted, resulting in the destruction of genetic material, proteins, and various organelles (including mitochondria) in cells. When various organelles such as mitochondria in cells are damaged, the cells have abnormal nutrition and metabolism, and ROS can further aggravate the damage of the\u00a0<a class=\"topic-link\" title=\"Learn more about vascular endothelium from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vascular-endothelium\">vascular endothelium<\/a>\u00a0and induce the disturbance of the\u00a0<a class=\"topic-link\" title=\"Learn more about microcirculation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/microcirculation\">microcirculation<\/a>\u00a0in the brain. The permeability disorder of the blood-brain barrier in the brain induces the overexpression of\u00a0<a class=\"topic-link\" title=\"Learn more about cell adhesion molecules from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cell-adhesion-molecule\">cell adhesion molecules<\/a>, thereby aggravating brain injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib122\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib122\"><span class=\"anchor-text\">[122]<\/span><\/a>. Meanwhile,\u00a0<a class=\"topic-link\" title=\"Learn more about oxidative stress from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/oxidative-stress\">oxidative stress<\/a>\u00a0causes cells to gradually exhibit a cell death mode characterized by increased\u00a0<a class=\"topic-link\" title=\"Learn more about cell membrane permeability from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cell-membrane-permeability\">cell membrane permeability<\/a>\u00a0and the release of cell contents &#8211; pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib120\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib120\"><span class=\"anchor-text\">[120]<\/span><\/a>. Therefore, both pyroptosis and mitochondrial damage are involved in the pathological process of cerebral ischemia-reperfusion injury. It has been reported that the mitochondrial motility-related protein Drp1 is a key protein necessary for mitochondria to maintain normal physiological functions\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib123\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib123\"><span class=\"anchor-text\">[123]<\/span><\/a>. When the expression of Drp1 is increased, it can inhibit the\u00a0<a class=\"topic-link\" title=\"Learn more about mitochondrial fission from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mitochondrial-fission\">mitochondrial fission<\/a>\u00a0process and reduce the level of pyroptosis, thereby slowing down the occurrence of damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib124\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib124\"><span class=\"anchor-text\">[124]<\/span><\/a>. When the body receives a variety of endogenous and exogenous damage stimuli, the regulatory process of signaling pathways in the body changes. It is manifested as decreased secretion of Drp1, mitochondrial damage, mitochondrial dysfunction, and increased apoptosis and pyroptosis, leading to various diseases in the body\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib125\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib125\"><span class=\"anchor-text\">[125]<\/span><\/a>. Recent studies show mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia\/reperfusion injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib126\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib126\"><span class=\"anchor-text\">[126]<\/span><\/a>. Mitochondrial\u00a0<a class=\"topic-link\" title=\"Learn more about uncoupling protein 2 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/uncoupling-protein-2\">uncoupling protein 2<\/a>\u00a0(UCP2) deficiency exacerbates brain injury after CIRI, and new studies show that UCP2 deficiency enhances NLRP3 inflammasome activation after hyperglycemia-induced CIRI exacerbation in vitro and in vivo. UCP2 may be a potential therapeutic target for hyperglycemia-induced worsening of CIRI. UCP2 deficiency also enhanced NLRP3 inflammasome activation and ROS production in neurons in vitro and in vivo\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib127\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib127\"><span class=\"anchor-text\">[127]<\/span><\/a>.\u00a0<a class=\"topic-link\" title=\"Learn more about Adiponectin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/adiponectin\">Adiponectin<\/a>\u00a0is an adipose-derived hormone with broad antioxidant and anti-inflammatory effects. Adiponectin peptide attenuates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK\/GSK-3\u03b2\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib128\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib128\"><span class=\"anchor-text\">[128]<\/span><\/a>. Therefore, in IS, there is a close relationship between the occurrence of pyroptosis and mitochondrial damage, and there is a close interaction between the two.<\/p>\n<\/section>\n<section id=\"sec0060\">\n<h3 id=\"sect0080\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">2.7.\u00a0Oxidative stress\/nitrosative stress mediates pyroptosis after IS<\/h3>\n<p id=\"p0100\">Oxidative\/nitrosative stress and\u00a0<a class=\"topic-link\" title=\"Learn more about neuroinflammation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neuroinflammation\">neuroinflammation<\/a>\u00a0are key\u00a0<a class=\"topic-link\" title=\"Learn more about pathological processes from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pathological-process\">pathological processes<\/a>\u00a0of cerebral ischemia-reperfusion injury, mediating neuronal damage, blood-brain barrier damage and hemorrhagic transformation during ischemic stroke\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib129\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib129\"><span class=\"anchor-text\">[129]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib130\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib130\"><span class=\"anchor-text\">[130]<\/span><\/a>. Nitric oxide (NO) and\u00a0<a class=\"topic-link\" title=\"Learn more about peroxynitrite from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/peroxynitrite\">peroxynitrite<\/a>\u00a0(ONOO-) are typical RNSs in CIRI\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib130\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib130\"><span class=\"anchor-text\">[130]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib131\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib131\"><span class=\"anchor-text\">[131]<\/span><\/a>. There are 3 isomers of\u00a0<a class=\"topic-link\" title=\"Learn more about nitric oxide synthase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nitric-oxide-synthase\">nitric oxide synthase<\/a>:\u00a0<a class=\"topic-link\" title=\"Learn more about endothelial nitric oxide synthase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/endothelial-nitric-oxide-synthase\">endothelial nitric oxide synthase<\/a>\u00a0(eNOS) produces low NO concentration and has physiological functions; while\u00a0<a class=\"topic-link\" title=\"Learn more about neuronal nitric oxide synthase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neuronal-nitric-oxide-synthase\">neuronal nitric oxide synthase<\/a>\u00a0(nNOS) and\u00a0<a class=\"topic-link\" title=\"Learn more about inducible nitric oxide synthase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/inducible-nitric-oxide-synthase\">inducible nitric oxide synthase<\/a>\u00a0(iNOS) produce high NO concentrations, which induces inflammation and increases blood-brain barrier permeability\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib132\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib132\"><span class=\"anchor-text\">[132]<\/span><\/a>. The overproduction of ROS\/RNS creates a stressful microenvironment and leads to a series of cellular signaling cascades, leading to inflammation, hyperpermeability of the blood-brain barrier,\u00a0<a class=\"topic-link\" title=\"Learn more about brain edema from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-edema\">brain edema<\/a>\u00a0and neuronal cell death\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib133\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib133\"><span class=\"anchor-text\">[133]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib134\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib134\"><span class=\"anchor-text\">[134]<\/span><\/a>. Peroxynitrite mediates\u00a0<a class=\"topic-link\" title=\"Learn more about DNA strand from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/dna-strand\">DNA strand<\/a>\u00a0breaks and activates the\u00a0<a class=\"topic-link\" title=\"Learn more about ribozyme from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ribozyme\">ribozyme<\/a>\u00a0poly(ADP-ribose) synthase (PARS), also known as poly(ADP-ribose) polymerase (PARP) or poly(ADPribose)\u00a0<a class=\"topic-link\" title=\"Learn more about transferase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/transferase\">transferase<\/a>\u00a0(pADPRT). ONOO- can directly activate PARP\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib135\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib135\"><span class=\"anchor-text\">[135]<\/span><\/a>, and in vivo and in vitro experiments have demonstrated the role of ONOO-\/PARP signaling pathway in ischemic brain injury. In vivo experiments showed that NOS-deficient mice displayed less PARP activation in an animal model of ischemic stroke. In vitro experiments showed that ONOO-donors, but not NO-donors, significantly induced PARP activation in cultured C6\u00a0<a class=\"topic-link\" title=\"Learn more about glioma cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/glioma-cell\">glioma cells<\/a>.\u00a0<a class=\"topic-link\" title=\"Learn more about Gene disruption from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/gene-disruption\">Gene disruption<\/a>\u00a0or silencing of PARP significantly reduces\u00a0<a class=\"topic-link\" title=\"Learn more about cerebral infarct size from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-infarction-size\">cerebral infarct size<\/a>, alleviates\u00a0<a class=\"topic-link\" title=\"Learn more about neurotoxicity from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neurotoxicity\">neurotoxicity<\/a>, protects neurovascular units and improves neurological outcomes\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib136\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib136\"><span class=\"anchor-text\">[136]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib137\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib137\"><span class=\"anchor-text\">[137]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib138\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib138\"><span class=\"anchor-text\">[138]<\/span><\/a>. Studies have found that ROS\/RNS may be an activator of the inflammasome during CIRI\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib139\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib139\"><span class=\"anchor-text\">[139]<\/span><\/a>. The inflammasome is a multi-protein complex in the cytoplasm of microglia, of which NOD-like receptor 3 (NLRP3) is the most widely studied one. NLRP3 triggers and activates caspase-1, activates IL-1\u03b2 and IL-18 and releases them into the\u00a0<a class=\"topic-link\" title=\"Learn more about extracellular space from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/extracellular-space\">extracellular space<\/a>, promoting the development of inflammation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib140\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib140\"><span class=\"anchor-text\">[140]<\/span><\/a>. In vivo experiments showed that the cerebral infarct size and BBB damage in NLPR3 knockout mice were lower than those in wild-type mice. Further experiments showed that NLRP3 could mediate the release of IL-1\u03b2 and increase the permeability of cerebral microvascular endothelial cells\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib141\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib141\"><span class=\"anchor-text\">[141]<\/span><\/a>. Nuclear factor E2-related\u00a0<a class=\"topic-link\" title=\"Learn more about factor 2 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/prothrombin\">factor 2<\/a>\u00a0(Nrf2) regulates cellular antioxidant responses, and Nrf2 inhibits ROS-mediated NLRP3 production in BV2 microglia under conditions of oxygen and glucose deprivation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib142\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib142\"><span class=\"anchor-text\">[142]<\/span><\/a>. It was found that oxidative\/nitrosative stress induces the formation of peroxynitrite, which may be a key trigger of caspase1\/inflammasome activation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib143\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib143\"><span class=\"anchor-text\">[143]<\/span><\/a>. Therefore, ROS\/RNS-mediated inflammasome may be a potential therapeutic target for ischemic brain injury.<\/p>\n<p id=\"p0105\">In addition, ROS\/RNS mediates the activation of Toll-like receptors. Current studies have shown that Toll-like receptors (TLRs) have been widely studied as an innate\u00a0<a class=\"topic-link\" title=\"Learn more about immune receptor from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/immune-system-receptors\">immune receptor<\/a>, and TLR4\/2 have been studied more in cerebral\u00a0<a class=\"topic-link\" title=\"Learn more about ischemic injury from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ischemic-injury\">ischemic injury<\/a>.\u00a0<a class=\"topic-link\" title=\"Learn more about TLR4 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/toll-like-receptor-4\">TLR4<\/a>\u00a0can mediate the expression of IL-1\u03b2, MMP-9, iNOS and COX-2, and aggravate oxidative stress-induced brain damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib144\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib144\"><span class=\"anchor-text\">[144]<\/span><\/a>. The application of the TLR4 inhibitor\u00a0<a class=\"topic-link\" title=\"Learn more about E5564 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/eritoran\">E5564<\/a>\u00a0showed that it can play a\u00a0<a class=\"topic-link\" title=\"Learn more about neuroprotective from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neuroprotective-agent\">neuroprotective<\/a>\u00a0role by inhibiting the activation of microglia and the production of ROS\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib145\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib145\"><span class=\"anchor-text\">[145]<\/span><\/a>. After IS, the infarct size of TLR4-deficient mice was significantly smaller than that of wild-type mice\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib146\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib146\"><span class=\"anchor-text\">[146]<\/span><\/a>. TLR4 is also involved in post-IS\u00a0<a class=\"topic-link\" title=\"Learn more about neurogenesis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neurogenesis\">neurogenesis<\/a>.\u00a0<a class=\"topic-link\" title=\"Learn more about Positron emission tomography from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/positron-emission-tomography\">Positron emission tomography<\/a>\u00a0studies have shown that TLR4-deficient mice have enhanced neurogenesis and suppressed inflammatory responses in IS\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib147\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib147\"><span class=\"anchor-text\">[147]<\/span><\/a>. In addition, in vivo experimental studies have shown that inhibiting the TLR2\/4\/NF-\u03baB signaling pathway has a certain effect on regulating oxidative stress, inflammatory response, and protecting ischemic brain tissue\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib148\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib148\"><span class=\"anchor-text\">[148]<\/span><\/a>. Therefore, TLR4\/2 may be a therapeutic target for ischemic brain injury.<\/p>\n<\/section>\n<\/section>\n<section id=\"sec0065\">\n<h2 id=\"sect0085\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">3.\u00a0The relationship between pyroptosis and IS<\/h2>\n<p id=\"p0110\">The pathological mechanisms of cerebral\u00a0<a class=\"topic-link\" title=\"Learn more about ischemia from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ischemia\">ischemia<\/a>\u00a0and post-ischemia-reperfusion injury are complex. The mechanisms involved in this process include inflammation, oxidative stress, autophagy, mitochondrial dysfunction, calcium overload, and programmed cell death\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib149\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib149\"><span class=\"anchor-text\">[149]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib150\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib150\"><span class=\"anchor-text\">[150]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib151\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib151\"><span class=\"anchor-text\">[151]<\/span><\/a>. A number of studies have shown that programmed cell death plays an important role in the pathological process of cerebral ischemia and ischemia-reperfusion injury, and is intertwined and closely related to the above mechanisms, especially pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib152\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib152\"><span class=\"anchor-text\">[152]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib153\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib153\"><span class=\"anchor-text\">[153]<\/span><\/a>. Programmed cell death is the main event of ischemic stroke, involving neurons,\u00a0<a class=\"topic-link\" title=\"Learn more about microglia from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/microglia\">microglia<\/a>, astrocytes,\u00a0<a class=\"topic-link\" title=\"Learn more about vascular endothelial cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vascular-endothelial-cell\">vascular endothelial cells<\/a>, etc., such as apoptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib154\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib154\"><span class=\"anchor-text\">[154]<\/span><\/a>, autophagy\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib155\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib155\"><span class=\"anchor-text\">[155]<\/span><\/a>, programmed necrosis or necroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib156\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib156\"><span class=\"anchor-text\">[156]<\/span><\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about ferroptosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ferroptosis\">ferroptosis<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib157\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib157\"><span class=\"anchor-text\">[157]<\/span><\/a>, and pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib158\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib158\"><span class=\"anchor-text\">[158]<\/span><\/a>. Especially in pyroptosis, the expression of pyroptosis-related proteins such as NLRP1, ASC, Caspase-1, and GSDMD is increased in a rat model of cerebral ischemia, and inhibition of NLRP1 can alleviate inflammation and cerebral\u00a0<a class=\"topic-link\" title=\"Learn more about ischemic injury from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ischemic-injury\">ischemic injury<\/a>. In addition, in the event of chronic cerebral ischemia, cells promote inflammatory responses by releasing signals such as DAMPs and\u00a0<a class=\"topic-link\" title=\"Learn more about PAMPs from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pathogen-associated-molecular-pattern\">PAMPs<\/a>, and trigger a series of complex molecular responses. At this time, intracranial neuroimmune inflammatory cells, such as microglia and astrocytes, appear to proliferate and activate, which further damages the neurovascular unit\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib159\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib159\"><span class=\"anchor-text\">[159]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib160\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib160\"><span class=\"anchor-text\">[160]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib161\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib161\"><span class=\"anchor-text\">[161]<\/span><\/a>.<\/p>\n<section id=\"sec0070\">\n<h3 id=\"sect0090\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">3.1.\u00a0Pyroptosis and neurons<\/h3>\n<p id=\"p0115\">After IS, necrosis occurs in the central ischemic area in a short time, and dead cells release danger signals such as\u00a0<a class=\"topic-link\" title=\"Learn more about HMGB1 protein from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/high-mobility-group-b1-protein\">HMGB1 protein<\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about heat shock protein from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/heat-shock-protein\">heat shock protein<\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about peroxidase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/peroxidase\">peroxidase<\/a>\u00a0family protein, etc. These danger signal molecules bind to\u00a0<a class=\"topic-link\" title=\"Learn more about pattern recognition receptors from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pattern-recognition-receptor\">pattern recognition receptors<\/a>, form\u00a0<a class=\"topic-link\" title=\"Learn more about inflammasomes from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/inflammasome\">inflammasomes<\/a>, initiate innate immune responses, and cause neuronal death\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib162\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib162\"><span class=\"anchor-text\">[162]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib163\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib163\"><span class=\"anchor-text\">[163]<\/span><\/a>. Studies have confirmed that cerebral ischemia can lead to the high expression of NLRP1 and\u00a0<a class=\"topic-link\" title=\"Learn more about NLRP3 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nucleotide-binding-oligomerization-domain-like-receptor\">NLRP3<\/a>\u00a0in ischemic brain tissue and neurons, and the activation of NLRP1 mainly exists in neurons\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib164\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib164\"><span class=\"anchor-text\">[164]<\/span><\/a>. The use of Caspase-1 inhibitors or immunoglobulin preparations can attenuate the expression of NLRP1 and NLRP3 in primary cortical neurons and reduce the size of\u00a0<a class=\"topic-link\" title=\"Learn more about cerebral infarction from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-infarction\">cerebral infarction<\/a>, and the mechanism may be related to the inhibition of NF-\u03baB and MAPK pathway activation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib164\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib164\"><span class=\"anchor-text\">[164]<\/span><\/a>. In the IS mice Li et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib165\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib165\"><span class=\"anchor-text\">[165]<\/span><\/a>\u00a0found that on the 3rd day after cerebral ischemia, ultrastructural damage of neuronal plasma, nuclear and\u00a0<a class=\"topic-link\" title=\"Learn more about mitochondrial membranes from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mitochondrial-membrane\">mitochondrial membranes<\/a>\u00a0occurred, and the expressions of Caspase-1, GSDMD and IL-1\u03b2 were significantly increased. The Caspase-1 inhibitor\u00a0<a class=\"topic-link\" title=\"Learn more about Vx765 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/belnacasan\">Vx765<\/a>\u00a0can inhibit pyroptosis, promote the survival of neurons in ischemic areas, and improve\u00a0<a class=\"topic-link\" title=\"Learn more about brain dysfunction from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-dysfunction\">brain dysfunction<\/a>\u00a0in mice. Liang et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib166\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib166\"><span class=\"anchor-text\">[166]<\/span><\/a>\u00a0found that long non-coding RNA maternally expressed gene 3 (MEG3) promotes pyroptosis and inflammatory responses by activating the AIM2\/Caspase-1 pathway, resulting in cerebral ischemia-reperfusion injury. Knockout of MEG3 gene can inhibit the expression of\u00a0<a class=\"topic-link\" title=\"Learn more about AIM2 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nodular-melanoma\">AIM2<\/a>, Caspase-1, GSDMD and other proteins, and alleviate ischemic brain injury. This suggests that MEG3 may be an effective therapeutic target for ischemic stroke.<\/p>\n<\/section>\n<section id=\"sec0075\">\n<h3 id=\"sect0095\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">3.2.\u00a0Pyroptosis and astrocytes<\/h3>\n<p id=\"p0120\">Astrocytes are the most abundant\u00a0<a class=\"topic-link\" title=\"Learn more about glial cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/glial-cells\">glial cells<\/a>\u00a0in the\u00a0<a class=\"topic-link\" title=\"Learn more about central nervous system from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/central-nervous-system\">central nervous system<\/a>\u00a0and are involved in the formation of the blood-brain barrier, regulating neuronal metabolism and stabilizing intercellular communication\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib167\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib167\"><span class=\"anchor-text\">[167]<\/span><\/a>. After IS, a prominent pathological change is reactive\u00a0<a class=\"topic-link\" title=\"Learn more about astrogliosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/astrocytosis\">astrogliosis<\/a>\u00a0and glial scarring, which promote neuronal plasticity early after ischemic injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib168\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib168\"><span class=\"anchor-text\">[168]<\/span><\/a>. It is generally believed that when the\u00a0<a class=\"topic-link\" title=\"Learn more about hippocampus from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/hippocampus\">hippocampus<\/a>\u00a0is ischemia and\u00a0<a class=\"topic-link\" title=\"Learn more about hypoxia from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/hypoxia\">hypoxia<\/a>, the\u00a0<a class=\"topic-link\" title=\"Learn more about antioxidant capacity from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/antioxidant-capacity\">antioxidant capacity<\/a>\u00a0of the hippocampus will be weakened, and a large number of inflammatory factors may be released, thereby aggravating the damage to the hippocampus\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib169\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib169\"><span class=\"anchor-text\">[169]<\/span><\/a>. Three (3) h after focal cerebral ischemia in\u00a0<a class=\"topic-link\" title=\"Learn more about SD rats from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/sprague-dawley-rat\">SD rats<\/a>, IL-1\u03b2-like immunoreactive positive cells appeared in the ischemic area, mainly inactivated astrocytes. Until 2 months after ischemia, the positive cells can still be detected in the ischemic hemisphere, especially around the necrotic foci, and the higher the degree of activation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib170\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib170\"><span class=\"anchor-text\">[170]<\/span><\/a>. Activated astrocytes can induce the release of\u00a0<a class=\"topic-link\" title=\"Learn more about tumor necrosis factor from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/tumor-necrosis-factor\">tumor necrosis factor<\/a>, interleukin, growth factor and other inflammatory factors or neuronal toxic mediators, resulting in neuronal damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib171\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib171\"><span class=\"anchor-text\">[171]<\/span><\/a>. NLRP2 is mainly expressed in astrocytes, but hardly expressed in neurons and microglia. Moreover, the expression of NLRP2 was significantly up-regulated in the mouse cerebral ischemia model and after oxygen and glucose deprivation in astrocytes, and silencing NLRP2 could reduce the pyroptosis induced by oxygen and glucose deprivation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib172\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib172\"><span class=\"anchor-text\">[172]<\/span><\/a>. Another study found that in an in vitro model of cerebral ischemia, oxygen-glucose deprivation led to an increase in NLRP3, ASC, Caspase-1, IL-1\u03b2, and IL-18, and a decrease in astrocyte survival.\u00a0<a class=\"topic-link\" title=\"Learn more about Hispidulin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/hispidulin\">Hispidulin<\/a>\u00a0is a ketone compound isolated from\u00a0<a class=\"topic-link\" title=\"Learn more about Chinese herbal medicine from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/chinese-herbal-medicine\">Chinese herbal medicine<\/a>. In vitro and in vivo experiments have shown that Hispidulin can inhibit NLRP3-mediated pyroptosis and exert a protective effect on the brain, and its mechanism is related to the activation of the AMPK\/GSK-3\u03b2\u00a0<a class=\"topic-link\" title=\"Learn more about signaling pathway from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/signal-transduction\">signaling pathway<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib173\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib173\"><span class=\"anchor-text\">[173]<\/span><\/a>. Meng et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib174\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib174\"><span class=\"anchor-text\">[174]<\/span><\/a>\u00a0found that the expression of NLRP6 reached a peak at 48\u2009h after cerebral ischemia-reperfusion in rats. After oxygen and glucose deprivation in astrocytes, the production of NLRP6 and its activation products increases, and silencing NLRP6 can reduce ASC and Caspase-1, reduce the release of inflammatory factors, and increase neuronal activity\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib175\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib175\"><span class=\"anchor-text\">[175]<\/span><\/a>. Therefore, interventions targeting inflammasome activation in astrocytes may provide new ideas for the treatment of IS.<\/p>\n<\/section>\n<section id=\"sec0080\">\n<h3 id=\"sect0100\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">3.3.\u00a0Pyroptosis and Microglia<\/h3>\n<p id=\"p0125\">Microglia are the innate\u00a0<a class=\"topic-link\" title=\"Learn more about immune cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/immunocompetent-cell\">immune cells<\/a>\u00a0of the central nervous system and the earliest activated cells after ischemic stroke\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib176\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib176\"><span class=\"anchor-text\">[176]<\/span><\/a>. In the acute phase of cerebral ischemia injury, microglia rapidly migrate to the lesion site and secrete inflammatory factors and cytotoxic substances, aggravating tissue damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib177\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib177\"><span class=\"anchor-text\">[177]<\/span><\/a>. In the chronic phase, microglia can produce anti-inflammatory cytokines and growth factors to promote\u00a0<a class=\"topic-link\" title=\"Learn more about tissue repair from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/tissue-repair\">tissue repair<\/a>\u00a0and remodeling\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib178\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib178\"><span class=\"anchor-text\">[178]<\/span><\/a>. Studies have found that microglial pyroptosis plays an important role in ischemic brain injury. NLRC4 was the first inflammasome to be significantly increased when microglia were deprived of oxygen and glucose for 3\u2009h, while NLRP1, NLRP3 and AIM2 were not significantly increased until after 6\u2009h of oxygen glucose deprivation. Silencing NLRC4 can reduce the production of GSDMD, IL-1\u03b2 and IL-18, and inhibit microglial pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib179\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib179\"><span class=\"anchor-text\">[179]<\/span><\/a>. Xu et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib180\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib180\"><span class=\"anchor-text\">[180]<\/span><\/a>\u00a0reported that driver receptor 1 (TREM-1) expressed by\u00a0<a class=\"topic-link\" title=\"Learn more about myeloid cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/myeloid-cell\">myeloid cells<\/a>\u00a0in microglia after cerebral ischemia-reperfusion can activate the NLRP3\/Caspase-1-mediated pyroptosis pathway and induce neuroinflammatory responses. Inhibition of TREM-1 reduces microglial pyroptosis and nerve damage. Li et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib181\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib181\"><span class=\"anchor-text\">[181]<\/span><\/a>\u00a0confirmed that the expression of cyclic guanosine monophosphate-adenosine synthase (cGAS) is up-regulated after cerebral ischemia and activates the AIM2 inflammasome to induce microglial pyroptosis. The cGAS antagonist A151 can inhibit AIM2 activation and microglial pyroptosis, significantly reduce cerebral infarct volume, and alleviate nerve damage. The above studies indicate that microglia pyroptosis and its mediated neuroinflammatory response may be an important mechanism leading to ischemic brain injury. Inhibiting the neurotoxic effects of microglia may be a new strategy for the treatment of ischemic stroke.<\/p>\n<\/section>\n<section id=\"sec0085\">\n<h3 id=\"sect0105\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">3.4.\u00a0Pyroptosis and endothelial cells<\/h3>\n<p id=\"p0130\">Endothelial cells constitute the first barrier of the blood-brain barrier, providing scaffolds for\u00a0<a class=\"topic-link\" title=\"Learn more about claudin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/claudin\">claudin<\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about adhesion molecules from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cell-adhesion-molecule\">adhesion molecules<\/a>\u00a0and\u00a0<a class=\"topic-link\" title=\"Learn more about extracellular matrix from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/extracellular-matrix\">extracellular matrix<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib182\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib182\"><span class=\"anchor-text\">[182]<\/span><\/a>. During cerebral ischemia, immune-inflammatory response and oxidative stress can damage\u00a0<a class=\"topic-link\" title=\"Learn more about endothelial cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/endothelial-cell\">endothelial cells<\/a>\u00a0and disrupt the integrity of the blood-brain barrier, leading to vasogenic edema, hemorrhagic transformation, and increased mortality\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib183\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib183\"><span class=\"anchor-text\">[183]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib184\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib184\"><span class=\"anchor-text\">[184]<\/span><\/a>. After cerebral ischemia, NLRP3 is up-regulated in neurons, microglia and vascular endothelial cells, and silencing NLRP3 gene can reduce the volume of cerebral infarction in mice with\u00a0<a class=\"topic-link\" title=\"Learn more about middle cerebral artery from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/middle-cerebral-artery\">middle cerebral artery<\/a>\u00a0ischemia and reduce the permeability of blood-brain barrier\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib185\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib185\"><span class=\"anchor-text\">[185]<\/span><\/a>. Wang et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib186\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib186\"><span class=\"anchor-text\">[186]<\/span><\/a>\u00a0confirmed that cerebral ischemia can induce pyroptosis of microvascular endothelial cells and aggravate ischemia-reperfusion injury. They also found that activation of peroxisome proliferator-activated receptor gamma coactivator 1\u03b1 (PGC-1\u03b1) significantly reduced the expression of pyroptosis-related proteins and increased the expression of ZO-1 and\u00a0<a class=\"topic-link\" title=\"Learn more about Occludin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/occludin\">Occludin<\/a>\u00a0proteins in brain microvascular endothelial cells, so as to protect the integrity of the blood-brain barrier. In addition, studies have found that the pyroptosis of cerebral microvascular endothelial cells may increase the possibility of hemorrhage after IS, leading to serious complications such as\u00a0<a class=\"topic-link\" title=\"Learn more about cerebral hemorrhage from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cerebral-hemorrhage\">cerebral hemorrhage<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib187\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib187\"><span class=\"anchor-text\">[187]<\/span><\/a>.<\/p>\n<div>\n<p id=\"p0135\">The association between cerebral ischemia and pyroptosis is summarized in\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#fig0010\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"fig0010\"><span class=\"anchor-text\">Fig. 2<\/span><\/a>.<\/p>\n<figure id=\"fig0010\" class=\"figure text-xs\"><img decoding=\"async\" src=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr2.jpg\" alt=\"Fig. 2\" height=\"362\" aria-describedby=\"cap0010\" \/><\/p>\n<ol class=\"u-margin-s-bottom\">\n<li><a class=\"anchor download-link u-font-sans u-display-inline anchor-default\" title=\"Download high-res image (274KB)\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr2_lrg.jpg\" target=\"_blank\" rel=\"noopener\" download=\"\"><span class=\"anchor-text\">Download :\u00a0<span class=\"download-link-title\">Download high-res image (274KB)<\/span><\/span><\/a><\/li>\n<li><a class=\"anchor download-link u-font-sans u-display-inline anchor-default\" title=\"Download full-size image\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr2.jpg\" target=\"_blank\" rel=\"noopener\" download=\"\"><span class=\"anchor-text\">Download :\u00a0<span class=\"download-link-title\">Download full-size image<\/span><\/span><\/a><\/li>\n<\/ol>\n<p id=\"sp0010\"><span class=\"label\">Fig. 2<\/span>.\u00a0Summary of the mechanism of pyroptosis in vascular neuronal units after IS [Molecular mechanism of pyroptosis on vascular neuronal units (consists of microglia, astrocytes, neurons,\u00a0<a class=\"topic-link\" title=\"Learn more about vascular endothelial cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vascular-endothelial-cell\">vascular endothelial cells<\/a>, pericytes) after IS. IRF:\u00a0<a class=\"topic-link\" title=\"Learn more about interferon regulatory factor from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/interferon-regulatory-factor\">interferon regulatory factor<\/a>; IFN:\u00a0<a class=\"topic-link\" title=\"Learn more about Interferon from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/interferon\">Interferon<\/a>; CASP: Caspase; GPX4: Glutathione peroxidase 4].<\/p>\n<\/figure>\n<\/div>\n<\/section>\n<\/section>\n<section id=\"sec0090\">\n<h2 id=\"sect0110\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">4.\u00a0Potential of pyroptosis inhibitors to treat IS<\/h2>\n<p id=\"p0140\">In recent years, the research of pyroptosis inhibitors in IS has received much attention. Liang et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib188\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib188\"><span class=\"anchor-text\">[188]<\/span><\/a>\u00a0found that the Caspase-1 inhibitor VX-765 can reduce Caspase-1, ASC, GSDMD and IL-1\u03b2, while up-regulating the levels of\u00a0<a class=\"topic-link\" title=\"Learn more about tight junction proteins from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/tight-junction-protein\">tight junction proteins<\/a>\u00a0and\u00a0<a class=\"topic-link\" title=\"Learn more about tissue inhibitors of metalloproteinases from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/metalloprotease-inhibitor\">tissue inhibitors of metalloproteinases<\/a>, protecting the integrity of the blood-brain barrier. In addition, VX-765 also promotes the transformation of microglia from M1 type to M2 type, reduce the inflammatory response mediated by microglia, and exert a neuroprotective effect\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib189\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib189\"><span class=\"anchor-text\">[189]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib190\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib190\"><span class=\"anchor-text\">[190]<\/span><\/a>. MCC950 is a selective NLRP3 inhibitor. Studies have found that MCC950 can reduce the expression of NLRP3, Caspase-1, and IL-1\u03b2 in the ischemic penumbra, and has a protective effect on focal cerebral ischemia in mice\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib191\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib191\"><span class=\"anchor-text\">[191]<\/span><\/a>. Studies have found that some\u00a0<a class=\"topic-link\" title=\"Learn more about microRNAs from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/microrna\">microRNAs<\/a>\u00a0may inhibit the pyroptosis in cerebral ischemia model and play a neuroprotective role\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib192\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib192\"><span class=\"anchor-text\">[192]<\/span><\/a>. LP17 may inhibit\u00a0<a class=\"topic-link\" title=\"Learn more about myeloid cell from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/myeloid-cell\">myeloid cell<\/a>\u00a0trigger receptor-1, thereby inhibiting oxidative stress and pyroptosis, and reducing cerebral ischemia-induced neuronal damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib192\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib192\"><span class=\"anchor-text\">[192]<\/span><\/a>.\u00a0<a class=\"topic-link\" title=\"Learn more about Histidine from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/histidine\">Histidine<\/a>\u00a0may inhibit NLRP3-mediated pyroptosis by regulating the adenylate-activated protein kinase\/glycogen synthase kinase-3\u03b2 signaling pathway, thereby exerting anti-CIRI neuroprotective effects\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib193\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib193\"><span class=\"anchor-text\">[193]<\/span><\/a>. Low-density lipoprotein receptors may inhibit NLRP3-mediated neuronal pyroptosis after CIRI\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib194\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib194\"><span class=\"anchor-text\">[194]<\/span><\/a>. The lipid alcohol-mediated peroxisome proliferator-activated receptor \u03b1-glutamate oxaloacetate transaminase 1 axis may inhibit the pyroptosis of endothelial cells after IS and improve ischemic brain injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib195\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib195\"><span class=\"anchor-text\">[195]<\/span><\/a>. Overexpression of CHRFAM7A may inhibit NLRP3\/caspase-1 pathway-dependent microglial pyroptosis and attenuate CIRI\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib196\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib196\"><span class=\"anchor-text\">[196]<\/span><\/a>. TP53-induced glycolysis and apoptosis regulators may alleviate cerebral ischemia-induced microglial pyroptosis and ischemic brain injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib197\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib197\"><span class=\"anchor-text\">[197]<\/span><\/a>. In addition,\u00a0<a class=\"topic-link\" title=\"Learn more about exosomes from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/exosome\">exosomes<\/a>\u00a0derived from hypoxic bone marrow\u00a0<a class=\"topic-link\" title=\"Learn more about mesenchymal stem cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mesenchymal-stem-cell\">mesenchymal stem cells<\/a>\u00a0may modulate the microglial M1\/M2 phenotype to alleviate CIRI-induced neuronal pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib198\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib198\"><span class=\"anchor-text\">[198]<\/span><\/a>. Hypoxia-preconditioned\u00a0<a class=\"topic-link\" title=\"Learn more about olfactory mucosa from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/olfactory-mucosa\">olfactory mucosa<\/a>\u00a0mesenchymal stem cells may inhibit the pyroptosis and apoptosis of microglia caused by cerebral ischemia by activating hypoxia-inducible factor-1\u03b1, thereby reducing CIRI\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib199\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib199\"><span class=\"anchor-text\">[199]<\/span><\/a>.<\/p>\n<p id=\"p0145\">As an executor of pyroptosis, GSDMD is an ideal molecular target for the treatment of IS. However, current research on GSDMD inhibitors is still in its infancy, and evidence of the efficacy of GSDMD inhibitors in the treatment of ischemic stroke is lacking. Recent studies have found that some natural plant components may treat IS by regulating the pyroptotic pathway.<\/p>\n<\/section>\n<section id=\"sec0095\">\n<h2 id=\"sect0115\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">5.\u00a0Natural products as novel pyroptosis inhibitors and thus become potential candidates for the treatment of IS<\/h2>\n<p id=\"p0150\">Natural products have significant advantages in the prevention and treatment of cerebral infarction\/cerebral ischemia-reperfusion due to their advantages of multi-component, multi-target, multi-channel and low toxicity, and have good application prospects. Currently, the research of natural products in the prevention and treatment of cerebral infarction\/CIRI is gradually increasing, involving a variety of protective mechanisms. This section summarized the natural products, animal or cell models, administration methods, administration doses, treatment time, effects, and treatment mechanisms (signaling pathways) to provide theoretical support for the rapid search for natural plant components that are safe, effective, low toxicity, and regulate pyroptosis for the prevention and treatment of IS\/CIRI.<\/p>\n<section id=\"sec0100\">\n<h3 id=\"sect0120\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">5.1.\u00a0Natural plant components<\/h3>\n<div>\n<p id=\"p0155\">The main structure of natural plant components were shown in\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#fig0015\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"fig0015\"><span class=\"anchor-text\">Fig. 3<\/span><\/a>.<\/p>\n<figure id=\"fig0015\" class=\"figure text-xs\"><img decoding=\"async\" src=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr3.jpg\" alt=\"Fig. 3\" height=\"397\" aria-describedby=\"cap0015\" \/><\/p>\n<ol class=\"u-margin-s-bottom\">\n<li><a class=\"anchor download-link u-font-sans u-display-inline anchor-default\" title=\"Download high-res image (208KB)\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr3_lrg.jpg\" target=\"_blank\" rel=\"noopener\" download=\"\"><span class=\"anchor-text\">Download :\u00a0<span class=\"download-link-title\">Download high-res image (208KB)<\/span><\/span><\/a><\/li>\n<li><a class=\"anchor download-link u-font-sans u-display-inline anchor-default\" title=\"Download full-size image\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0753332222013889-gr3.jpg\" target=\"_blank\" rel=\"noopener\" download=\"\"><span class=\"anchor-text\">Download :\u00a0<span class=\"download-link-title\">Download full-size image<\/span><\/span><\/a><\/li>\n<\/ol>\n<p id=\"sp0015\"><span class=\"label\">Fig. 3<\/span>.\u00a0The main structure of natural plant components.<\/p>\n<\/figure>\n<\/div>\n<section id=\"sec0105\">\n<h4 id=\"sect0125\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.1.\u00a0Gastrodin (GAS)<\/h4>\n<p id=\"p0160\">GAS is a multifunctional compound derived from the herb,\u00a0<em><a class=\"topic-link\" title=\"Learn more about Gastrodia elata from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/gastrodia-elata\">Gastrodia elata<\/a><\/em>, with various\u00a0<a class=\"topic-link\" title=\"Learn more about pharmacological activities from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/pharmacological-activity\">pharmacological activities<\/a>, such as antioxidant and anti-inflammatory activities. In addition, GAS has been shown to significantly reduce symptoms of cerebral ischemia-reperfusion by modulating pro-apoptotic factors including caspase-3 cleavage, IL-18, and IL-1\u03b2. Several studies have shown that GAS ameliorates cerebral ischemic injury and reduces the levels of\u00a0<a class=\"topic-link\" title=\"Learn more about reactive oxygen species from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/reactive-oxygen-species\">reactive oxygen species<\/a>\u00a0and\u00a0<a class=\"topic-link\" title=\"Learn more about inflammatory cytokines from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/inflammatory-cytokine\">inflammatory cytokines<\/a>\u00a0in mice\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib200\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib200\"><span class=\"anchor-text\">[200]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib201\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib201\"><span class=\"anchor-text\">[201]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib202\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib202\"><span class=\"anchor-text\">[202]<\/span><\/a>. Lu et al. found that GAS could ameliorate pyroptosis associated with cardiac microvascular ischemia-reperfusion injury by targeting the NLRP3\/caspase-1 axis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib203\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib203\"><span class=\"anchor-text\">[203]<\/span><\/a>. GAS may significantly improve the\u00a0<a class=\"topic-link\" title=\"Learn more about neurological function from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nervous-system-physiology\">neurological function<\/a>\u00a0score and reduce the size of\u00a0<a class=\"topic-link\" title=\"Learn more about cerebral infarction from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-infarction\">cerebral infarction<\/a>. Meanwhile, GAS inhibited pyroptosis by downregulating NLRP3, inflammatory factors (IL-1\u03b2, IL-18) and cleaved caspase-1. Furthermore, GAS attenuated ischemia-reperfusion-induced neuronal cell inflammation by regulating the lncRNA NEAT1\/miR-22\u20133p axis. GAS significantly attenuated cerebral ischemia-reperfusion injury by regulating the lncRNA NEAT1\/miR-22\u20133p axis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib204\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib204\"><span class=\"anchor-text\">[204]<\/span><\/a>. Therefore, GAS may be used as a potential\u00a0<a class=\"topic-link\" title=\"Learn more about drug from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/chemotherapeutic-agent\">drug<\/a>\u00a0for the treatment of CIRI.<\/p>\n<\/section>\n<section id=\"sec0110\">\n<h4 id=\"sect0130\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.2.\u00a0Tanshinone IIA<\/h4>\n<p id=\"p0165\"><a class=\"topic-link\" title=\"Learn more about Tanshinone IIA from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/tanshinone-iia\">Tanshinone IIA<\/a>\u00a0is the main active component of\u00a0<em><a class=\"topic-link\" title=\"Learn more about Salvia miltiorrhiza from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/salvia-miltiorrhiza\">Salvia miltiorrhiza<\/a><\/em>. It is widely used in the treatment of cardiovascular and\u00a0<a class=\"topic-link\" title=\"Learn more about cerebrovascular diseases from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cerebrovascular-disease\">cerebrovascular diseases<\/a>\u00a0due to its anti-oxidative and circulation-improving effects. Cai et al.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib205\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib205\"><span class=\"anchor-text\">[205]<\/span><\/a>\u00a0found that tanshinone IIA effectively reduced the expression of IL-1\u03b2 and IL-18 in the NLRP3 inflammatory signaling pathway, and its effect is dose-dependent. This suggests that tanshinone IIA inhibits the activation of NLRP3 signaling pathway, thereby reducing the damage of oxygen-glucose deprivation\/reperfusion on BV-2 cells after stroke.<\/p>\n<\/section>\n<section id=\"sec0115\">\n<h4 id=\"sect0135\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.3.\u00a0Leonurine<\/h4>\n<p id=\"p0170\"><a class=\"topic-link\" title=\"Learn more about Leonurine from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/leonurine\">Leonurine<\/a>\u00a0in\u00a0<em><a class=\"topic-link\" title=\"Learn more about Leonuri from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/leonurus\">Leonuri<\/a><\/em><em>\u00a0herba<\/em>\u00a0improved the learning ability and memory ability of rats with chronic cerebral ischemia, and reduced the expression of NLRP3. It is speculated that the purpose of protecting nerves may be achieved through anti-inflammatory effect. Activation of NLRP3 promoted the conversion of Caspase-1 precursor to Caspase-1, and promoted the production of IL-1\u03b2 and IL-18, thereby causing a series of inflammatory responses. Leonurine may reduce the inflammatory response in brain tissue, reduce the neurological deficit score by inhibiting the pyroptosis of cells, and has a good neuroprotective effect\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib206\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib206\"><span class=\"anchor-text\">[206]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0120\">\n<h4 id=\"sect0140\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.4.\u00a0Paeoniflorin<\/h4>\n<p id=\"p0175\"><a class=\"topic-link\" title=\"Learn more about Paeoniflorin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/paeoniflorin\">Paeoniflorin<\/a>\u00a0comes from the main component of\u00a0<em><a class=\"topic-link\" title=\"Learn more about Paeoniae radix rubra from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/radix-paeoniae-rubra\">Paeoniae radix rubra<\/a><\/em>. Paeoniflorin is the main active component of total glucosides of\u00a0<a class=\"topic-link\" title=\"Learn more about peony from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/paeonia\">peony<\/a>\u00a0(TGP), which also has good anti-inflammatory and immunomodulatory activities\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib207\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib207\"><span class=\"anchor-text\">[207]<\/span><\/a>. TGP and paeoniflorin also have various pharmacological activities such as\u00a0<a class=\"topic-link\" title=\"Learn more about antispasmodic from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/antispasmodic\">antispasmodic<\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about analgesic from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/anodyne\">analgesic<\/a>, and\u00a0<a class=\"topic-link\" title=\"Learn more about vasodilation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vasodilatation\">vasodilation<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib208\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib208\"><span class=\"anchor-text\">[208]<\/span><\/a>. Zulifiya Ekemu et al. found that after acute cerebral ischemia-reperfusion, the activation of microglia and neuronal pyroptosis in the brain was obvious, the activation of NLRP3 was increased, and Caspase-1 and IL-1\u03b2 were up-regulated\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib209\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib209\"><span class=\"anchor-text\">[209]<\/span><\/a>. Paeoniflorin significantly reduced neurological function scores, significantly reduced\u00a0<a class=\"topic-link\" title=\"Learn more about cerebral infarct size from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-infarction-size\">cerebral infarct size<\/a>, significantly down-regulated Iba1 expression, and significantly improved neuronal status. In addition, the expressions of NLRP3, Caspase-1 and IL-1\u03b2 were significantly decreased after paeoniflorin intervention. It is suggested that paeoniflorin may reduce the activation of microglia, inhibit neuron pyroptosis, and improve ACI-mediated neurological damage by inhibiting the activation of NLRP3 and Caspase-1\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib209\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib209\"><span class=\"anchor-text\">[209]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0125\">\n<h4 id=\"sect0145\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.5.\u00a0Butylphthalide<\/h4>\n<p id=\"p0180\"><span class=\"small-caps\">L<\/span>-butylphthalide was first isolated from cress seeds, and later it could be synthesized artificially.\u00a0<a class=\"topic-link\" title=\"Learn more about Butylphthalide from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/butylphthalide\">Butylphthalide<\/a>\u00a0has a unique dual role, which can not only reconstruct\u00a0<a class=\"topic-link\" title=\"Learn more about microcirculation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/microcirculation\">microcirculation<\/a>\u00a0and increase ischemia reperfusion, thereby protecting the integrity of\u00a0<a class=\"topic-link\" title=\"Learn more about vascular structure from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/blood-vessel\">vascular structure<\/a>, restoring vascular diameter, increasing blood flow in ischemic area and the number of surrounding\u00a0<a class=\"topic-link\" title=\"Learn more about microvessels from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/microvessel\">microvessels<\/a>, but also protecting mitochondria and reducing cell death, thereby protecting the integrity of mitochondrial structure, improving the activity of mitochondrial complex enzyme IV, improving the activity of mitochondrial ATP enzyme and maintaining the stability of\u00a0<a class=\"topic-link\" title=\"Learn more about mitochondrial membrane from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mitochondrial-membrane\">mitochondrial membrane<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib210\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib210\"><span class=\"anchor-text\">[210]<\/span><\/a>. The latest study shows the butylphthalide may affect pyroptosis in CIRI rats in a dose-dependent manner through the NLRP3 inflammasome signaling pathway.<\/p>\n<\/section>\n<section id=\"sec0130\">\n<h4 id=\"sect0150\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.6.\u00a0Breviscapine<\/h4>\n<p id=\"p0185\"><a class=\"topic-link\" title=\"Learn more about Breviscapine from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/breviscapine\">Breviscapine<\/a>\u00a0is extracted from\u00a0<em><a class=\"topic-link\" title=\"Learn more about Erigeron breviscapus from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/erigeron-breviscapus\">Erigeron breviscapus<\/a><\/em>\u00a0(Vant.) Hand. -Mazz. Breviscapine is a mixture of\u00a0<a class=\"topic-link\" title=\"Learn more about scutellarin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/scutellarin\">scutellarin<\/a>\u00a0mainly containing scutellarin with a small amount of scutellarin, which has the functions of dilating cerebral blood vessels, reducing cerebrovascular resistance, increasing cerebral blood flow, improving microcirculation, and resisting\u00a0<a class=\"topic-link\" title=\"Learn more about platelet aggregation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/thrombocyte-aggregation\">platelet aggregation<\/a>. The latest research shows that breviscapine significantly inhibited the activation of NLRP3 inflammatory cells in the\u00a0<a class=\"topic-link\" title=\"Learn more about hippocampus from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/hippocampus\">hippocampus<\/a>\u00a0of CCI rats, down-regulate the expression of Caspase 1, IL-6 and IL-1\u03b2 protein, inhibit the activation of Caspase-3 protein, and inhibit\u00a0<a class=\"topic-link\" title=\"Learn more about neuronal apoptosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neuroapoptosis\">neuronal apoptosis<\/a>. This suggests that breviscapine may significantly improve the cognitive function of CCI rats and reduce the pathological damage of ischemic neurons, and its mechanism may be related to the inhibition of NLRP3 inflammasome activation and pyroptosis pathway in brain tissue\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib211\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib211\"><span class=\"anchor-text\">[211]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0135\">\n<h4 id=\"sect0155\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.7.\u00a0Resveratrol<\/h4>\n<p id=\"p0190\"><a class=\"topic-link\" title=\"Learn more about Resveratrol from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/resveratrol\">Resveratrol<\/a>\u00a0is a non-flavonoid\u00a0<a class=\"topic-link\" title=\"Learn more about polyphenolic compound from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/polyphenol-derivative\">polyphenolic compound<\/a>. It was first isolated from the roots of\u00a0<em><a class=\"topic-link\" title=\"Learn more about Veratrum from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/veratrum\">Veratrum<\/a><\/em><em>\u00a0grandiflorum<\/em>, and resveratrol has been found in more than 700 plants. Studies have shown that resveratrol plays an important role in regulating oxidative stress in cerebral infarction, inhibiting inflammation, and improving brain\u00a0<a class=\"topic-link\" title=\"Learn more about neuroprotection from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neuroprotection\">neuroprotection<\/a>. Resveratrol regulates the pyroptosis of ischemia-reperfusion brain tissue mainly through the regulation of microglia NLRP3 inflammasome, Caspase-1 and ZO-1\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib212\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib212\"><span class=\"anchor-text\">[212]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0140\">\n<h4 id=\"sect0160\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.8.\u00a0Salvianolic acid (SAFI)<\/h4>\n<p id=\"p0195\">Recent studies have shown that SAFI significantly increased neurological deficit scores, reduce infarct volume, attenuate histological damage to\u00a0<a class=\"topic-link\" title=\"Learn more about cerebral cortex from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cerebral-cortex\">cerebral cortex<\/a>\u00a0and neuronal apoptosis in MCAO\/R model, increase neuronal viability and reduce neuronal apoptosis in OGD model. SAFI also remodeled the microglial polarization pattern from an M1-like phenotype to an M2-like phenotype and inhibited the activation of the NLRP3 inflammasome and the expression of NLRP3 inflammasome\/pyroxia-related proteins in vitro and in vivo. This suggests that SAFI may exert neuroprotective effects by reducing neuronal apoptosis, shifting the microglial phenotype from M1 to M2, and inhibiting the NLRP3 inflammasome\/pyroptotic axis in microglia\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib213\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib213\"><span class=\"anchor-text\">[213]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0145\">\n<h4 id=\"sect0165\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.9.\u00a0Hispidulin<\/h4>\n<p id=\"p0200\"><a class=\"topic-link\" title=\"Learn more about Hispidulin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/hispidulin\">Hispidulin<\/a>\u00a0is a\u00a0<a class=\"topic-link\" title=\"Learn more about flavonoid from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/flavonoid\">flavonoid<\/a>\u00a0compound with various pharmacological properties and is one of the main active components of many\u00a0<a class=\"topic-link\" title=\"Learn more about Chinese herbal medicines from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/chinese-herbal-medicine\">Chinese herbal medicines<\/a>. Hispidulin has a wide range of pharmacological properties, including antioxidant,\u00a0<a class=\"topic-link\" title=\"Learn more about antifungal from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/antifungal-agent\">antifungal<\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about antineoplastic from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/anticarcinogen\">antineoplastic<\/a>, antiosteoporotic, antiinflammatory and antimutagenic properties. The latest study showed that Hispidulin improved\u00a0<a class=\"topic-link\" title=\"Learn more about neurological symptoms from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neurologic-disease\">neurological symptoms<\/a>\u00a0in rats after IRI, while reducing infarct size and\u00a0<a class=\"topic-link\" title=\"Learn more about brain edema from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/brain-edema\">brain edema<\/a>. Mechanistically, hispidulin exerts its neuroprotective effects in vivo and in vitro by inhibiting NLRP3-mediated pyroptosis by regulating the AMPK\/GSK3\u03b2 signaling pathway\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib214\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib214\"><span class=\"anchor-text\">[214]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0150\">\n<h4 id=\"sect0170\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.10.\u00a0Astragaloside IV<\/h4>\n<p id=\"p0205\"><em><a class=\"topic-link\" title=\"Learn more about Astragali Radix from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/astragalus-root\">Astragali Radix<\/a><\/em>\u00a0can supplement deficiency, strengthen the spleen and stomach, promote blood circulation and promote blood circulation, and can treat the symptoms of\u00a0<a class=\"topic-link\" title=\"Learn more about Qi deficiency from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/qi-deficiency\">Qi deficiency<\/a>\u00a0and blood deficiency\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib215\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib215\"><span class=\"anchor-text\">[215]<\/span><\/a>.\u00a0<a class=\"topic-link\" title=\"Learn more about Astragaloside IV from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/astragaloside-iv\">Astragaloside IV<\/a>\u00a0is one of the main active components of\u00a0<em>Astragali Radix<\/em>\u00a0and the\u00a0<a class=\"topic-link\" title=\"Learn more about monomer from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/monomer\">monomer<\/a>\u00a0component of\u00a0<a class=\"topic-link\" title=\"Learn more about Astragalus from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/astragalus\">Astragalus<\/a>\u00a0<a class=\"topic-link\" title=\"Learn more about saponins from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/saponin\">saponins<\/a>. It is often used as a standard for testing the quality of Astragalus\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib216\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib216\"><span class=\"anchor-text\">[216]<\/span><\/a>. Astragaloside IV has a variety of\u00a0<a class=\"topic-link\" title=\"Learn more about biological activities from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/biological-activity\">biological activities<\/a>, and the research scope involves multiple organs and tissues such as brain, liver, heart, lung, kidney, stomach, intestine, blood vessels, etc.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib217\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib217\"><span class=\"anchor-text\">[217]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib218\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib218\"><span class=\"anchor-text\">[218]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib219\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib219\"><span class=\"anchor-text\">[219]<\/span><\/a>\u00a0It has biological activities such as anti-inflammatory, anti-virus, anti-apoptosis, promoting\u00a0<a class=\"topic-link\" title=\"Learn more about cell proliferation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cell-proliferation\">cell proliferation<\/a>, regulating\u00a0<a class=\"topic-link\" title=\"Learn more about rabbit disease from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/rabbit-disease\">rabbit disease<\/a>, regulating blood sugar, slowing down aging, and inhibiting cancer\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib217\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib217\"><span class=\"anchor-text\">[217]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib218\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib218\"><span class=\"anchor-text\">[218]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib219\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib219\"><span class=\"anchor-text\">[219]<\/span><\/a>. Our previous study identified astragaloside IV as a potential neuroprotective agent that played an important role in the treatment of IS. For example, it can protect the blood-brain barrier, improve energy metabolism, inhibit nerve cell apoptosis, inhibit inflammatory response, oxidative stress, and exert neuroprotective effects, thereby improving cerebral ischemia\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib220\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib220\"><span class=\"anchor-text\">[220]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib221\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib221\"><span class=\"anchor-text\">[221]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib222\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib222\"><span class=\"anchor-text\">[222]<\/span><\/a>. In terms of pyroptosis, Tang et al. found that NLRP3 inflammasome was activated during cerebral ischemia-reperfusion in rats, and inhibiting NLRP3 inflammasome or inhibiting its downstream Caspase-1 could alleviate cerebral ischemia-reperfusion in rats damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib223\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib223\"><span class=\"anchor-text\">[223]<\/span><\/a>. Astragaloside IV can reduce the neurological deficit score, reduce the volume of cerebral infarction, and reduce the protein levels of NLRP3, Caspase-1, pro-IL-1\u03b2, IL-1\u03b2, pro-IL-18 and IL-18 in brain tissue, and inhibit the expression of phosphorylated NF-\u03baB protein. This suggests that astragaloside IV has an anti-CIRI effect, and its mechanism may be related to the inhibition of NF-\u03baB\u00a0<a class=\"topic-link\" title=\"Learn more about protein phosphorylation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/protein-phosphorylation\">protein phosphorylation<\/a>\u00a0and the inhibition of NLRP3 inflammasome activation\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib223\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib223\"><span class=\"anchor-text\">[223]<\/span><\/a>. Li et al. also found that astragaloside IV can reduce hypoxia-ischemia-induced brain damage in neonatal rats, and inhibit the inflammatory response of hypoxic-ischemic brain tissue and HT22 hippocampal neurons in neonatal rats, which may be exerted by regulating MMP-9-mediated NLRP3\/Caspase-1 signaling pathway\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib224\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib224\"><span class=\"anchor-text\">[224]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0155\">\n<h4 id=\"sect0175\" class=\"u-margin-m-top u-margin-xs-bottom\">5.1.11.\u00a0Panax notoginseng saponins (PNS)<\/h4>\n<p id=\"p0210\"><em>Notoginseng Radix Et Rhizoma<\/em>\u00a0is the dried root and\u00a0<a class=\"topic-link\" title=\"Learn more about rhizome from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/rhizome\">rhizome<\/a>\u00a0of\u00a0<em><a class=\"topic-link\" title=\"Learn more about Panax from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/panax\">Panax<\/a><\/em><em>\u00a0notoginsen (Burk.)<\/em>\u00a0F. H. Chen, which has pharmacological activity in blood, cardiovascular, nervous and immune systems\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib225\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib225\"><span class=\"anchor-text\">[225]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib226\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib226\"><span class=\"anchor-text\">[226]<\/span><\/a>. PNS is its main active ingredient, containing a variety of monomeric saponins, and its preparations such as Xuesaitong injection are widely used in the prevention and treatment of cardiovascular and cerebrovascular diseases\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib227\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib227\"><span class=\"anchor-text\">[227]<\/span><\/a>. Our previous studies and existing studies have shown that PNS has various pharmacological effects in ischemic brain injury, such as\u00a0<a class=\"topic-link\" title=\"Learn more about antithrombotic from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/antithrombotic\">antithrombotic<\/a>, anti-inflammatory, antioxidant, inhibiting brain nerve cell apoptosis, and improving blood-brain barrier damage\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib228\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib228\"><span class=\"anchor-text\">[228]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib229\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib229\"><span class=\"anchor-text\">[229]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib230\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib230\"><span class=\"anchor-text\">[230]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib231\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib231\"><span class=\"anchor-text\">[231]<\/span><\/a>. This suggests that PNS may play a protective role in cerebral ischemia through multiple targets. Recent studies have found that PNS can inhibit the activation of the NLRP3 inflammasome and selectively promote\u00a0<a class=\"topic-link\" title=\"Learn more about mitophagy from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/mitophagy\">mitophagy<\/a>\u00a0during cerebral ischemia-reperfusion in rats. Inhibition of mitophagy could reverse the inhibitory effect of PNS on NLRP3 inflammasome, indicating that mitophagy mediates the inhibitory effect of PNS on NLRP3 inflammasome activation in cerebral ischemia-reperfusion. In addition, the levels of PINK1 and Parkin proteins in mitochondria increased during cerebral ischemia-reperfusion in rats, and PNS could further increase the levels of PINK1 and Parkin proteins in mitochondria of brain tissue. This suggests that PNS may promote mitophagy in cerebral ischemia-reperfusion through the PINK1\/Parkin pathway\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib232\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib232\"><span class=\"anchor-text\">[232]<\/span><\/a>. In summary, PNS selectively promotes mitophagy through the PINK1\/Parkin pathway, inhibits the activation of NLRP3 inflammasome in cerebral ischemia-reperfusion, and alleviates cerebral ischemia-reperfusion injury.<\/p>\n<\/section>\n<\/section>\n<section id=\"sec0160\">\n<h3 id=\"sect0180\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\">5.2.\u00a0Natural plant extract<\/h3>\n<section id=\"sec0165\">\n<h4 id=\"sect0185\" class=\"u-margin-m-top u-margin-xs-bottom\">5.2.1.\u00a0Taohong Siwu Decoction (THSWD)<\/h4>\n<p id=\"p0215\">THSWD is one of the classic prescriptions for promoting blood circulation and removing\u00a0<a class=\"topic-link\" title=\"Learn more about blood stasis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/blood-stasis\">blood stasis<\/a>, removing blood stasis and regenerating new blood created by Wu Qian&#8217;s &#8220;Golden Mirror of Medicine&#8221; in Qing Dynasty. Current pharmacological studies have confirmed that the main active ingredients of THSWD include\u00a0<a class=\"topic-link\" title=\"Learn more about ferulic acid from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ferulic-acid\">ferulic acid<\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about safflower from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/safflower\">safflower<\/a>\u00a0yellow, and\u00a0<a class=\"topic-link\" title=\"Learn more about polysaccharides from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/glycan\">polysaccharides<\/a>. Among them, ferulic acid has pharmacological effects such as inhibiting platelet aggregation, antithrombotic, anti-inflammatory and anti-oxidation. Safflower yellow has anti-cerebral ischemia, anti-myocardial ischemia, anti-thrombosis, antioxidant, anti-tumor and other effects. Zhou et al. found that THSWD improved the neurological deficit function, cerebral infarction volume and brain tissue morphology after cerebral ischemia-reperfusion injury, and significantly reduced the levels of DRP1, NLRP3, Caspase-1 and IL-1 \u03b2 proteins\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib233\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib233\"><span class=\"anchor-text\">[233]<\/span><\/a>. It indicated that the therapeutic effect of THSWD on cerebral infarction was related to the inhibition of DRP1\/NLRP3 pathway related to pyroptosis. Further research showed that the contents of IL-1\u03b2 and IL-18 in the THSWD group were significantly decreased, and the levels of NLRP3, Caspase-1, Caspase-1 p10, ASC, TXNIP, and GSDMD were decreased. The detection of signaling pathways showed that THSWD significantly reduced the expression levels of HMGB1\/RAGE, TLR4\/NF-\u03baB,\u00a0<a class=\"topic-link\" title=\"Learn more about p38 MAPK from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/p38-mitogen-activated-protein-kinase\">p38 MAPK<\/a>\u00a0and JNK in the penumbra. In summary, THSWD reduced the level of inflammatory response in MCAO\/R rats, inhibit the activation of NLRP3 inflammasome in MCAO\/R rats, and down-regulate GSDMD. THSWD has the effect of inhibiting pyroptosis, which may be affected by inhibiting HMGB1\/TLR4\/NF-kB and MAPK signaling pathways\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib234\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib234\"><span class=\"anchor-text\">[234]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0170\">\n<h4 id=\"sect0190\" class=\"u-margin-m-top u-margin-xs-bottom\">5.2.2.\u00a0Naoxinqing Capsules (NXQC)<\/h4>\n<p id=\"p0220\">The main ingredient of NXQC is the leaf of\u00a0<em><a class=\"topic-link\" title=\"Learn more about Diospyros kaki from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/persimmon\">Diospyros kaki<\/a><\/em>\u00a0Thunb (persimmon leaf). Studies have shown that persimmon leaf extract contains flavonoids, organic acids and\u00a0<a class=\"topic-link\" title=\"Learn more about coumarin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/coumarin\">coumarin<\/a>\u00a0and other chemicals, which have the effects of anti-inflammatory, antioxidant,\u00a0<a class=\"topic-link\" title=\"Learn more about antihypertensive from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/antihypertensive-agent\">antihypertensive<\/a>, blood lipid lowering, improving\u00a0<a class=\"topic-link\" title=\"Learn more about vascular smooth muscle from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vascular-smooth-muscle\">vascular smooth muscle<\/a>\u00a0function and\u00a0<a class=\"topic-link\" title=\"Learn more about hemodynamic from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/hemodynamic\">hemodynamic<\/a>\u00a0function. The drug has been widely used in the treatment of cardiovascular and cerebrovascular diseases\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib235\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib235\"><span class=\"anchor-text\">[235]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib236\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib236\"><span class=\"anchor-text\">[236]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib237\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib237\"><span class=\"anchor-text\">[237]<\/span><\/a>. Existing studies have shown that NXQC can effectively improve\u00a0<a class=\"topic-link\" title=\"Learn more about cerebral arteriosclerosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cerebral-atherosclerosis\">cerebral arteriosclerosis<\/a>\u00a0and protect nerve damage caused by cerebral ischemia\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib238\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib238\"><span class=\"anchor-text\">[238]<\/span><\/a>. Min et al. found that NXQC can effectively improve the decline of learning ability after cerebral ischemia, and increase the activities of\u00a0<a class=\"topic-link\" title=\"Learn more about superoxide dismutase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/superoxide-dismutase\">superoxide dismutase<\/a>\u00a0and\u00a0<a class=\"topic-link\" title=\"Learn more about lactate dehydrogenase from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/lactate-dehydrogenase\">lactate dehydrogenase<\/a>, increase the content of GSH, and reduce the content of\u00a0<a class=\"topic-link\" title=\"Learn more about malondialdehyde from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/malonaldehyde\">malondialdehyde<\/a>. NXQC can also down-regulate ASC, NLRP3 and Caspase-1 proteins in hippocampus, and significantly reduce IL-18 and IL-1\u03b2 contents. They also found that the platelet endothelial cell adhesion molecule-1 positive cells in gerbils were significantly increased after the intervention with NXQC, and the\u00a0<a class=\"topic-link\" title=\"Learn more about intercellular junctions from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/cell-junction\">intercellular junctions<\/a>\u00a0were tight. It is suggested that NXQC can effectively protect the morphology of\u00a0<a class=\"topic-link\" title=\"Learn more about hippocampal CA1 region from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/sommers-sector\">hippocampal CA1 region<\/a>\u00a0of gerbils, protect cerebrovascular function, and then inhibit cerebral ischemia-reperfusion injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib239\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib239\"><span class=\"anchor-text\">[239]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0175\">\n<h4 id=\"sect0195\" class=\"u-margin-m-top u-margin-xs-bottom\">5.2.3.\u00a0Buyang Huanwu Decoction (BYHWD) and Its Modifications<\/h4>\n<p id=\"p0225\">BYHWD is a famous\u00a0<a class=\"topic-link\" title=\"Learn more about traditional Chinese medicine from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/traditional-chinese-medicine\">traditional Chinese medicine<\/a>\u00a0formula used to treat stroke. Its prescription was first recorded in Wang Qingren&#8217;s &#8220;Medical Classics Correction&#8221; in the Qing Dynasty\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib240\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib240\"><span class=\"anchor-text\">[240]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib241\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib241\"><span class=\"anchor-text\">[241]<\/span><\/a>. It is an outstanding representative of the prescription for nourishing qi and activating blood. It has the functions of tonifying qi, promoting blood circulation and dredging collaterals. Its evidence-based medicine studies have shown good clinical effects\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib242\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib242\"><span class=\"anchor-text\">[242]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib243\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib243\"><span class=\"anchor-text\">[243]<\/span><\/a>. Our previous study showed that BYHWD\u00a0<a class=\"topic-link\" title=\"Learn more about glycosides from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/glycoside\">glycosides<\/a>\u00a0can improve neurological dysfunction, reduce neuronal damage, and inhibit neuronal pyroptosis. BYHWD glycosides are the active ingredients extracted from BYHWD, mainly including astragaloside IV, paeoniflorin and\u00a0<a class=\"topic-link\" title=\"Learn more about amygdalin from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/amygdalin\">amygdalin<\/a>. It is the main pharmacological active ingredient of tonifying kidney and activating blood, and can treat cerebral ischemic nerve injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib244\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib244\"><span class=\"anchor-text\">[244]<\/span><\/a>. Furthermore, we observed that BYHWD glycosides significantly inhibited the expression of NLRP3, ASC, pro-caspase-1, caspase-1 and IL-1\u03b2 proteins of the NLRP3-mediated canonical pyroptosis pathway\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib209\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib209\"><span class=\"anchor-text\">[209]<\/span><\/a>. In summary, BYHWD glycosides exert neuroprotective effects by inhibiting neuronal pyroptosis after CIRI, which is closely related to the regulation of classical pyroptotic pathway by NLRP3. In addition, Longzhi\u00a0<a class=\"topic-link\" title=\"Learn more about Decoction from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/decoction\">Decoction<\/a>\u00a0is an empirical formula formed by BYHWD with leeches and\u00a0<a class=\"topic-link\" title=\"Learn more about Achyranthes from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/achyranthes\">Achyranthes<\/a>\u00a0sichuanensis. It has been used in the clinical treatment of acute stroke for many years, and the effect is very good\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib245\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib245\"><span class=\"anchor-text\">[245]<\/span><\/a>. Recent studies have shown that Longzhi Decoction has obvious effects on improving neurological symptoms in rats after CIRI, maintaining the state of nerve cells in brain tissue, and reducing the volume of cerebral infarction. In terms of intervening cell pyroptosis, Longzhi Decoction can improve the symptoms of rats after CIRI and protect\u00a0<a class=\"topic-link\" title=\"Learn more about nerve cell damage from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nerve-cell-lesion\">nerve cell damage<\/a>\u00a0after injury by down-regulating the expression of Caspase-1 and IL-18 proteins\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib245\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib245\"><span class=\"anchor-text\">[245]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0180\">\n<h4 id=\"sect0200\" class=\"u-margin-m-top u-margin-xs-bottom\">5.2.4.\u00a0Yiqi Huoxue Prescription (YQHXP)<\/h4>\n<p id=\"p0230\">YQHXP consists of\u00a0<em>Angelicae Sinensis Radix, Astragali Radix,\u00a0<\/em><em><a class=\"topic-link\" title=\"Learn more about Chuanxiong Rhizoma from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/ligusticum-chuanxiong-extract\">Chuanxiong Rhizoma<\/a><\/em><em>, Scorpio, Leonuri Herba, Acori Tatarinowii Rhizoma, Borneolum Syntheticum<\/em>, and has achieved good clinical results\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib246\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib246\"><span class=\"anchor-text\">[246]<\/span><\/a>. Animal studies have shown that YQHXP improved neurological function scores and cerebral infarction rates in rats, and reduce the levels of IL-1\u03b2, TNF-\u03b1, and IL-18 in brain tissue, and the relative expression of\u00a0<a class=\"topic-link\" title=\"Learn more about P2RX7 from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/p2rx7\">P2RX7<\/a>, Caspase-1, Caspase-11, and GSDMD in cerebral ischemic penumbra tissue. After YQHXP intervention, the inflammatory exudation and edema of brain tissue were significantly reduced, and the cell morphology and neuronal vacuolar degeneration were improved. In summary, YQHXP may reduce brain tissue inflammation in acute ischemic stroke rats by inhibiting pyroptosis\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib247\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib247\"><span class=\"anchor-text\">[247]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0185\">\n<h4 id=\"sect0205\" class=\"u-margin-m-top u-margin-xs-bottom\">5.2.5.\u00a0Shen Nao Fu Yuan Decoction (SNFYD)<\/h4>\n<p id=\"p0235\">SNFYD is an effective prescription for ischemic stroke based on the theory of simultaneous treatment of kidney and brain. Its composition is:\u00a0<em>Astragali Radix<\/em>\u00a030\u2009g<em>,\u00a0<\/em><em><a class=\"topic-link\" title=\"Learn more about Rehmanniae from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/rehmannia\">Rehmanniae<\/a><\/em><em>\u00a0Radix Praeparata<\/em>\u00a010\u2009g<em>, Corni Fructus<\/em>\u00a010\u2009g<em>, Dioscoreae Rhizoma<\/em>\u00a015\u2009g<em>, Rhodiolae Crenulatae Radix Et Rhizoma<\/em>\u00a020\u2009g<em>,\u00a0<\/em><em><a class=\"topic-link\" title=\"Learn more about Moutan Cortex from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/moutan-cortex\">Moutan Cortex<\/a><\/em>\u00a010\u2009g<em>, Angelicae Sinensis Radix<\/em>\u00a010\u2009g<em>, Paeoniae Radix Rubra<\/em>\u00a010\u2009g<em>,\u00a0<\/em><em><a class=\"topic-link\" title=\"Learn more about Pheretima from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/pheretima\">Pheretima<\/a><\/em>\u00a010\u2009g\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib248\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib248\"><span class=\"anchor-text\">[248]<\/span><\/a>. It is combined with a large number of qi-invigorating, essence-replenishing and kidney-invigorating medicines, which are combined with activating blood and dredging collaterals. Studies have shown that after OGD modeling, PC12 was significantly damaged, and various cytokines in the pyroptosis pathway were significantly increased\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib249\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib249\"><span class=\"anchor-text\">[249]<\/span><\/a>. After SNFYD-containing serum and INF39 intervened in damaged\u00a0<a class=\"topic-link\" title=\"Learn more about PC12 cells from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pc12-cell-line\">PC12 cells<\/a>, the morphology and activity of PC12 cells were improved, and the activation of the NLRP3\/Caspase-1 pyroptosis pathway was weakened accordingly. It indicated that the inhibition of this pathway was related to the improvement of cell state, and both SNFYD and INF39 could inhibit the activation of this pathway. It is suggested that SNFYD may reduce the inflammatory apoptosis of nerve cells by inhibiting NLRP3\/Caspase-1 and downstream pyroptosis pathway, thereby protecting nerve tissue and achieving the purpose of treating cerebral infarction\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib250\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib250\"><span class=\"anchor-text\">[250]<\/span><\/a>.<\/p>\n<\/section>\n<section id=\"sec0190\">\n<h4 id=\"sect0210\" class=\"u-margin-m-top u-margin-xs-bottom\">5.2.6.\u00a0Other extracts<\/h4>\n<p id=\"p0240\">In addition, recent studies have shown that antithrombotic drugs such as heparin can improve lung injury by inhibiting pyroptosis. For example, Yang et al. found that heparin inhibits lung endothelial cell apoptosis by blocking hMGB1 LPS-induced caspase-11 activation, which may be a potential way to treat sepsis-induced lung injury\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib251\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib251\"><span class=\"anchor-text\">[251]<\/span><\/a>. Prathapan et al. found that tender coconut water has antioxidant and antithrombotic effects in an\u00a0<a class=\"topic-link\" title=\"Learn more about experimental myocardial infarction from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/experimental-myocardial-infarction\">experimental myocardial infarction<\/a>\u00a0model\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib252\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib252\"><span class=\"anchor-text\">[252]<\/span><\/a>, while young coconut juice can significantly reduce some of the pathologies associated with\u00a0<a class=\"topic-link\" title=\"Learn more about Alzheimer's disease from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/alzheimer-disease\">Alzheimer&#8217;s disease<\/a>\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib253\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib253\"><span class=\"anchor-text\">[253]<\/span><\/a>. It is indicated that coconut water may be a potential inhibitor of pyroptosis, and its role in regulating pyroptosis in IS may be studied in the future.<\/p>\n<p id=\"p0245\"><span class=\"small-caps\">L<\/span>-arginine is an organic compound that is present in\u00a0<a class=\"topic-link\" title=\"Learn more about protamine from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/protamine\">protamine<\/a>\u00a0in large amounts\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib254\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib254\"><span class=\"anchor-text\">[254]<\/span><\/a>. It is a precursor for the synthesis of\u00a0<a class=\"topic-link\" title=\"Learn more about nitric oxide from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nitric-oxide\">nitric oxide<\/a>\u00a0(NO), which protects the intact endothelium of blood vessels, acts as a\u00a0<a class=\"topic-link\" title=\"Learn more about vasodilator from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/vasodilator-agent\">vasodilator<\/a>\u00a0and an endogenous anti-atherosclerotic molecule\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib254\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib254\"><span class=\"anchor-text\">[254]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib255\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib255\"><span class=\"anchor-text\">[255]<\/span><\/a>. Animal experiments show that\u00a0<span class=\"small-caps\">L<\/span>-arginine may have complex\u00a0<a class=\"topic-link\" title=\"Learn more about anticoagulation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/anticoagulation\">anticoagulation<\/a>, anticoagulation and\u00a0<a class=\"topic-link\" title=\"Learn more about fibrinolysis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/fibrinolysis\">fibrinolysis<\/a>\u00a0effects\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib255\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib255\"><span class=\"anchor-text\">[255]<\/span><\/a>,\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib256\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib256\"><span class=\"anchor-text\">[256]<\/span><\/a>. In hypertensive rats, Cylwik et al. found that\u00a0<span class=\"small-caps\">L<\/span>-arginine could reduce blood pressure in rats, and long-term treatment shortened the euglobulin clot dissolution time and bleeding time, and inhibited collagen-induced platelet aggregation. It is suggested that\u00a0<span class=\"small-caps\">L<\/span>-arginine plays an antithrombotic effect in a hypertensive rat model of\u00a0<a class=\"topic-link\" title=\"Learn more about venous thrombosis from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/phlebothrombosis\">venous thrombosis<\/a>\u00a0in a complex manner\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib256\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib256\"><span class=\"anchor-text\">[256]<\/span><\/a>. A recent study showed that\u00a0<span class=\"small-caps\">L<\/span>-arginine may be a potential inhibitor of pyroptosis: Tanuseputero et al. suggested that\u00a0<span class=\"small-caps\">L<\/span>-arginine may partially inhibit the NLRP3 inflammasome to alleviate sepsis-induced\u00a0<a class=\"topic-link\" title=\"Learn more about acute kidney injury from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/acute-kidney-injury\">acute kidney injury<\/a>\u00a0in mice\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib257\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib257\"><span class=\"anchor-text\">[257]<\/span><\/a>. In view of the vasodilatory, antithrombotic and inhibiting NLRP3 inflammasome activities of\u00a0<span class=\"small-caps\">L<\/span>-arginine, it is suggested that\u00a0<span class=\"small-caps\">L<\/span>-arginine may have the potential to increase blood flow in the ischemic area and inhibit pyroptosis in IS.<\/p>\n<div>\n<p id=\"p0250\">The summary of natural products regulating pyroptosis is showed in\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#tbl0010\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"tbl0010\"><span class=\"anchor-text\">Table 2<\/span><\/a>.<\/p>\n<div id=\"tbl0010\" class=\"tables colsep-0 rowsep-0 frame-topbot\">\n<p id=\"sp0025\"><span class=\"label\">Table 2<\/span>.\u00a0The summary of natural compounds regulating pyroptosis.<\/p>\n<div class=\"groups\">\n<table>\n<thead>\n<tr class=\"rowsep-1\">\n<th scope=\"col\">Natural products<\/th>\n<th scope=\"col\">Model\/Disease<\/th>\n<th scope=\"col\">Species<\/th>\n<th scope=\"col\">Effects<\/th>\n<th scope=\"col\">Reference<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<th scope=\"row\">Gastrodin<\/th>\n<td>Middle Cerebral Artery Occlusion\/Reperfusion (MCAO\/R), Oxygen-glucose deprivation\/reoxygenation (OGD\/R)<\/td>\n<td>Rattus norvegicus and rimary cortical neurons from Rattus norvegicus<\/td>\n<td>Inhibits pyroptosis by downregulating NLRP3, inflammatory factors (IL-1\u03b2, IL-18) and cleaved caspase-1; regulates lncRNA NEAT1\/miR-22\u20133p axis and lncRNA NEAT1\/miR-22\u20133p axis<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib204\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib204\"><span class=\"anchor-text\">[204]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Tanshinone IIA<\/th>\n<td>OGD\/R<\/td>\n<td>BV2 cells (microglia from Mus musculus)<\/td>\n<td>Reduces the expression of IL-1\u03b2 and IL-18 in the NLRP3 inflammatory signaling pathway<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib205\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib205\"><span class=\"anchor-text\">[205]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Leonurine<\/th>\n<td>MCAO<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Reduces the expression of NLRP3<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib206\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib206\"><span class=\"anchor-text\">[206]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Paeoniflorin<\/th>\n<td>MCAO<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Inhibits NLRP3, Caspase-1 and IL-1\u03b2 level<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib209\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib209\"><span class=\"anchor-text\">[209]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Butylphthalide<\/th>\n<td>MCAO<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Regulates NLRP3 inflammasome signaling pathway<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib210\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib210\"><span class=\"anchor-text\">[210]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Breviscapine<\/th>\n<td>MCAO\/R<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Inhibits the activation of NLRP3 inflammatory cells in the hippocampus of CCI rats, down-regulates the expression of Caspase 1, IL-6 and IL-1\u03b2 protein, inhibits the activation of Caspase-3 protein<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib211\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib211\"><span class=\"anchor-text\">[211]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Resveratrol<\/th>\n<td>MCAO\/R<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Regulates microglia NLRP3 inflammasome, Caspase-1 and ZO-1<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib212\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib212\"><span class=\"anchor-text\">[212]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Salvianolic acid<\/th>\n<td>MCAO\/R and OGD\/R<\/td>\n<td>Rattus norvegicus and microglia from Rattus norvegicus<\/td>\n<td>Inhibites the activation of the NLRP3 inflammasome and the expression of NLRP3 inflammasome\/pyroxia-related proteins<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib213\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib213\"><span class=\"anchor-text\">[213]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Hispidulin<\/th>\n<td>MCAO<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Inhibites NLRP3-mediated pyroptosis by regulating the AMPK\/GSK3\u03b2 signaling pathway<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib214\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib214\"><span class=\"anchor-text\">[214]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Astragaloside IV<\/th>\n<td>MCAO\/R<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Inhibites the activation of NLRP3 inflammasome; reduces the protein levels of NLRP3, Caspase-1, pro-IL-1\u03b2, IL-1\u03b2, pro-IL-18 and IL-18 in brain tissue; inhibits the expression of phosphorylated NF-\u03baB protein<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib223\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib223\"><span class=\"anchor-text\">[223]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Panax notoginseng saponins<\/th>\n<td>MCAO\/R<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Regulates PINK1\/Parkin pathway; inhibits the activation of NLRP3 inflammasome<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib232\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib232\"><span class=\"anchor-text\">[232]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Taohong Siwu Decoction<\/th>\n<td>MCAO<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Reduces the levels of DRP1, NLRP3, Caspase-1 and IL-1 \u03b2 proteins<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib233\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib233\"><span class=\"anchor-text\">[233]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Taohong Siwu Decoction<\/th>\n<td>MCAO\/R<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Inhibites HMGB1\/TLR4\/NF-kB and MAPK signaling pathways<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib234\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib234\"><span class=\"anchor-text\">[234]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Naoxinqing Capsules<\/th>\n<td>MCAO\/R<\/td>\n<td>Meriones unguiculatus<\/td>\n<td>Down-regulates ASC, NLRP3 and Caspase-1 proteins; Reduces IL-18 and IL-1\u03b2 contents.<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib239\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib239\"><span class=\"anchor-text\">[239]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Buyang Huanwu Decoction<\/th>\n<td>MCAO\/R<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Inhibits the expression of NLRP3, ASC, pro-caspase-1, caspase-1 and IL-1\u03b2 proteins of the NLRP3-mediated canonical pyroptosis pathway<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib244\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib244\"><span class=\"anchor-text\">[244]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Longzhi Decoction<\/th>\n<td>MCAO\/R<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Down-regulates the expression of Caspase-1 and IL-18 proteins<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib245\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib245\"><span class=\"anchor-text\">[245]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Yiqi Huoxue Prescription<\/th>\n<td>MCAO<\/td>\n<td>Rattus norvegicus<\/td>\n<td>Reduces the levels of IL-1\u03b2, TNF-\u03b1, and IL-18 and the relative expression of P2RX7, Caspase-1, Caspase-11, and GSDMD<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib247\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib247\"><span class=\"anchor-text\">[247]<\/span><\/a><\/td>\n<\/tr>\n<tr>\n<th scope=\"row\">Shen Nao Fu Yuan Decoction<\/th>\n<td>OGD<\/td>\n<td>PC12 cells from Rattus norvegicus<\/td>\n<td>Inhibites NLRP3\/Caspase-1<\/td>\n<td><a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bib250\" data-sd-ui-side-panel-opener=\"true\" data-xocs-content-type=\"reference\" data-xocs-content-id=\"bib250\"><span class=\"anchor-text\">[250]<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n<\/section>\n<\/section>\n<section id=\"sec0195\">\n<h2 id=\"sect0215\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">6.\u00a0Prospects<\/h2>\n<p id=\"p0255\">Our research team has long studied the programmed cell death mode of various groups of cells (such as neurons, microglia, and astrocytes) in the vascular neural unit after IS. Combined with other research reports, we found that various cell death modes such as apoptosis, ferroptosis, and autophagy occurred after IS, and the morphology of apoptosis and pyroptosis had certain similarities.\u00a0<a class=\"topic-link\" title=\"Learn more about Neuroinflammation from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/neuroinflammation\">Neuroinflammation<\/a>\u00a0after IS is the most important pathological process leading to brain injury, in which pyroptosis is an important part of neuroinflammation. This suggests that pyroptosis is abnormally important in neuroinflammation-related programmed cell death after cerebral ischemia. The related signaling pathways triggered by pyroptosis also intersect with other programmed cell death pathways, suggesting that drug development targeting pyroptosis is an important way to treat IS.<\/p>\n<p id=\"p0260\">For the current study, there are still areas for improvement: (1) Due to the problems of normalization and unification in the animal model of the current study, the conclusions about pyroptosis in different cells of the\u00a0<a class=\"topic-link\" title=\"Learn more about nervous system from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/nervous-system\">nervous system<\/a>\u00a0are inconsistent. Therefore, in the future research on pyroptosis requires a more standardized and unified stable model in animal models of ischemic stroke, which can also determine the real effect of anti-pyroptosis drugs. (2) Future studies can verify the long-term brain-protective effects of natural compounds and the mechanisms regulating pyroptosis in a variety of rodent and large mammal stroke models. In the future, more attention should be paid to the\u00a0<a class=\"topic-link\" title=\"Learn more about pharmacokinetics from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pharmacokinetics\">pharmacokinetics<\/a>,\u00a0<a class=\"topic-link\" title=\"Learn more about pharmacodynamics from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/pharmacodynamics\">pharmacodynamics<\/a>, and toxicological properties of natural compounds that currently modulate pyroptosis. (3) In addition, the synergistic effect of the combination of natural compounds in regulating pyroptosis in cerebral ischemic stroke and the neuroprotective effect of inhibiting neuroinflammation need to be explored in the future. (4) If all results are favorable, the next step is to conduct\u00a0<a class=\"topic-link\" title=\"Learn more about clinical trials from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/clinical-trial\">clinical trials<\/a>\u00a0of potential\u00a0<a class=\"topic-link\" title=\"Learn more about phytochemicals from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/phytochemical\">phytochemicals<\/a>\u00a0to investigate their neuroprotective effects on cerebral ischemia\/stroke (For example, the team is currently conducting a clinical trial of Naotai Fang in the treatment of cerebral small vessel disease: ChiCTR1900024524).<\/p>\n<\/section>\n<section id=\"sec0200\">\n<h2 id=\"sect0220\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">7.\u00a0Summary<\/h2>\n<p id=\"p0265\">Pyroptosis, as a pro-inflammatory programmed cell death, plays an important role in the pathological process of ischemic stroke by inducing cell death and neuroinflammation mainly through the classical pyroptotic pathway mediated by Caspase-1. The relationship between non-canonical pyroptotic pathways and IS remains to be elucidated. Other mechanisms for pyroptosis require further study in the future. At present, studies have confirmed that\u00a0<a class=\"topic-link\" title=\"Learn more about drugs targeting from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/drug-delivery-system\">drugs targeting<\/a>\u00a0key proteins of the pyroptosis pathway can alleviate ischemic brain injury to a certain extent, but their research is mainly limited to cell and animal experiments, and there is a lack of\u00a0<a class=\"topic-link\" title=\"Learn more about clinical research from ScienceDirect's AI-generated Topic Pages\" href=\"https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/clinical-research\">clinical research<\/a>\u00a0evidence. Therefore, further clinical research to explore the regulatory mechanism of pyroptosis in IS is expected to provide novel therapeutic strategies and theoretical basis for the prevention and treatment of ischemic stroke. Regarding the regulation of pyroptosis by natural compounds, through our generalization, it can be found that natural plant compounds can regulate cerebral ischemia by regulating pyroptosis not only on a single component. Multicomponent natural plant compounds can also be seen to exhibit potential synergistic effects in modulating the inflammatory cascade triggered by pyroptosis. This inspires us to study the regulatory effects of various natural compounds on pyroptosis-mediated neuroinflammation caused by different signaling pathways in the future.<\/p>\n<\/section>\n<section id=\"sec0205\">\n<h2 id=\"sect0225\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">CRediT authorship contribution statement<\/h2>\n<p id=\"p0270\"><strong>Kailin Yang:<\/strong>\u00a0Conceptualization, Methodology, Formal analysis, Investigation, Writing \u2013 original draft;\u00a0<strong>Liuting Zeng:<\/strong>\u00a0Conceptualization, Methodology, Software, Formal analysis, Investigation, Writing \u2013 original draft;\u00a0<strong>Jinsong Zeng:<\/strong>\u00a0Methodology, Formal analysis, Investigation;\u00a0<strong>Tingting Bao:<\/strong>\u00a0Methodology, Formal analysis, Investigation, Writing \u2013 original draft;\u00a0<strong>Xiao Yuan:<\/strong>\u00a0Methodology, Formal analysis, Investigation;\u00a0<strong>Shanshan Wang:<\/strong>\u00a0Methodology, Formal analysis, Investigation;\u00a0<strong>Wang Xiang:<\/strong>\u00a0Methodology, Formal analysis, Investigation;\u00a0<strong>Hao Xu:<\/strong>\u00a0Methodology, Formal analysis, Investigation;\u00a0<strong>Jinwen Ge:<\/strong>\u00a0Conceptualization, Methodology, Formal analysis, Investigation, Writing \u2013 review &amp; editing.<\/p>\n<\/section>\n<\/div>\n<section id=\"coi0005\">\n<h2 id=\"sect0230\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">Conflict of\u00a0Interest Statement<\/h2>\n<p id=\"p0275\">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<\/p>\n<\/section>\n<section id=\"ack0005\">\n<h2 id=\"sect0235\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">Acknowledgements<\/h2>\n<p id=\"p0280\">This work is supported by the\u00a0<span id=\"gs1\">National Natural Science Foundation of China<\/span>\u00a0(<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#gs1\"><span class=\"anchor-text\">81774174<\/span><\/a>), the\u00a0<span id=\"gs2\">National Key Research and Development Project of China<\/span>\u00a0(No.\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#gs2\"><span class=\"anchor-text\">2018YFC1704904<\/span><\/a>),\u00a0<span id=\"gs3\">National Natural Science Foundation of Hunan Province<\/span>, China (<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#gs3\"><span class=\"anchor-text\">2020JJ5424<\/span><\/a>\u00a0and\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#gs3\"><span class=\"anchor-text\">2020JJ5442<\/span><\/a>),\u00a0<span id=\"gs4\">Hunan University of Chinese Medicine &#8220;Double First-Class&#8221; Discipline Open Fund Project of Integrated Traditional Chinese and Western Medicine<\/span>\u00a0(<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#gs4\"><span class=\"anchor-text\">2020ZXYJH08<\/span><\/a>\u00a0and\u00a0<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#gs4\"><span class=\"anchor-text\">2020ZXYJH09<\/span><\/a>),\u00a0<span id=\"gs5\">Hunan Provincial Department of Education Youth Fund Project<\/span>\u00a0(<a class=\"anchor u-display-inline anchor-paragraph\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#gs5\"><span class=\"anchor-text\">21B0386<\/span><\/a>).<\/p>\n<\/section>\n<\/div>\n<div class=\"text-content u-font-serif\">\n<section id=\"da0005\">\n<h2 id=\"sect0020\" class=\"u-h4 u-margin-l-top u-margin-xs-bottom\">Availability of data\u00a0and materials<\/h2>\n<p id=\"p0020\">The data used to support the findings of this study are included within the article.<\/p>\n<\/section>\n<\/div>\n<div class=\"Tail text-s\"><\/div>\n<section id=\"bibliog0005\" class=\"bibliography u-font-serif text-s\">\n<h2 class=\"section-title u-h4 u-margin-l-top u-margin-xs-bottom\">References<\/h2>\n<section id=\"bb0005\" class=\"bibliography-sec\">\n<ol id=\"reference-links-bb0005\" class=\"references\">\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib1\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib1\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[1]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">L.E.\u00a0Evans,\u00a0J.L.\u00a0Taylor,\u00a0C.J.\u00a0Smith,\u00a0H.A.T.\u00a0Pritchard,\u00a0A.S.\u00a0Greenstein,\u00a0S.M.\u00a0Allan<\/div>\n<div id=\"ref-id-sbref1\" class=\"title text-m\">Cardiovascular comorbidities, inflammation, and cerebral small vessel disease<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Cardiovasc Res.,\u00a0117\u00a0(13)\u00a0(2021), pp.\u00a02575-2588,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1093\/cvr\/cvab284\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1093\/cvr\/cvab284<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\">\n<p><a class=\"es-link found icon-small\" target=\"_blank\" rel=\"noopener\">\u00a0<span class=\"text\">View PDF<\/span>\u00a0<\/a><\/p>\n<div class=\"tooltip-container left\">\n<div class=\"icon\"><\/div>\n<p class=\"message\">This article is free to access.<\/p>\n<\/div>\n<\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85121137397&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref1\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Cardiovascular%20comorbidities%2C%20inflammation%2C%20and%20cerebral%20small%20vessel%20disease&amp;publication_year=2021&amp;author=L.E.%20Evans&amp;author=J.L.%20Taylor&amp;author=C.J.%20Smith&amp;author=H.A.T.%20Pritchard&amp;author=A.S.%20Greenstein&amp;author=S.M.%20Allan\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref1\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib2\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib2\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[2]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">P.\u00a0Han,\u00a0W.\u00a0Zhang,\u00a0L.\u00a0Kang,\u00a0Y.\u00a0Ma,\u00a0L.\u00a0Fu,\u00a0L.\u00a0Jia,\u00a0H.\u00a0Yu,\u00a0X.\u00a0Chen,\u00a0L.\u00a0Hou,\u00a0L.\u00a0Wang,\u00a0X.\u00a0Yu,\u00a0M.\u00a0Kohzuki,\u00a0Q.\u00a0Guo<\/div>\n<div id=\"ref-id-sbref2\" class=\"title text-m\">Clinical Evidence of Exercise Benefits for Stroke<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Adv. 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Prim.,\u00a08\u00a0(1)\u00a0(2022), p.\u00a012,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1038\/s41572-022-00337-x\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1038\/s41572-022-00337-x<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\"><a class=\"es-link found-doi icon-small\" target=\"_blank\" rel=\"noopener\"><span class=\"text\">View article<\/span>\u00a0<\/a><\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85125345650&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref4\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Childhood%20stroke&amp;publication_year=2022&amp;author=P.B.%20Sporns&amp;author=H.J.%20Fullerton&amp;author=S.%20Lee&amp;author=H.%20Kim&amp;author=W.D.%20Lo&amp;author=M.T.%20Mackay&amp;author=M.%20Wildgruber\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref4\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib5\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib5\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[5]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">M.Y.\u00a0Wu,\u00a0G.T.\u00a0Yiang,\u00a0W.T.\u00a0Liao,\u00a0A.P.\u00a0Tsai,\u00a0Y.L.\u00a0Cheng,\u00a0P.W.\u00a0Cheng,\u00a0C.Y.\u00a0Li,\u00a0C.J.\u00a0Li<\/div>\n<div id=\"ref-id-sbref5\" class=\"title text-m\">Current mechanistic concepts in ischemia and reperfusion injury<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Cell PhysiolBiochem,\u00a046\u00a0(4)\u00a0(2018), pp.\u00a01650-1667,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1159\/000489241\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1159\/000489241<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\">\n<p><a class=\"es-link found icon-small\" target=\"_blank\" rel=\"noopener\">\u00a0<span class=\"text\">View PDF<\/span>\u00a0<\/a><\/p>\n<div class=\"tooltip-container left\">\n<div class=\"icon\"><\/div>\n<p class=\"message\">This article is free to access.<\/p>\n<\/div>\n<\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85046014150&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref5\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Current%20mechanistic%20concepts%20in%20ischemia%20and%20reperfusion%20injury&amp;publication_year=2018&amp;author=M.Y.%20Wu&amp;author=G.T.%20Yiang&amp;author=W.T.%20Liao&amp;author=A.P.%20Tsai&amp;author=Y.L.%20Cheng&amp;author=P.W.%20Cheng&amp;author=C.Y.%20Li&amp;author=C.J.%20Li\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref5\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib6\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib6\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[6]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">K.\u00a0Furie<\/div>\n<div id=\"ref-id-sbref6\" class=\"title text-m\">Epidemiology and primary prevention of stroke<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Contin. 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Res,\u00a041\u00a0(3)\u00a0(2020), pp.\u00a0220-230,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.24272\/j.issn.2095-8137.2020.042\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.24272\/j.issn.2095-8137.2020.042<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\"><a class=\"es-link found-doi icon-small\" target=\"_blank\" rel=\"noopener\"><span class=\"text\">View article<\/span>\u00a0<\/a><\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85084692954&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref9\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=The%20pathological%20role%20of%20ferroptosis%20in%20ischemiareperfusion-related%20injury&amp;publication_year=2020&amp;author=H.F.%20Yan&amp;author=Q.Z.%20Tuo&amp;author=Q.Z.%20Yin&amp;author=P.%20Lei\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref9\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib10\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib10\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[10]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">M.Y.\u00a0Wu,\u00a0G.T.\u00a0Yiang,\u00a0W.T.\u00a0Liao,\u00a0A.P.\u00a0Tsai,\u00a0Y.L.\u00a0Cheng,\u00a0P.W.\u00a0Cheng,\u00a0C.Y.\u00a0Li,\u00a0C.J.\u00a0Li<\/div>\n<div id=\"ref-id-sbref10\" class=\"title text-m\">Current Mechanistic Concepts in Ischemia and Reperfusion Injury<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Cell PhysiolBiochem,\u00a046\u00a0(4)\u00a0(2018), pp.\u00a01650-1667,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1159\/000489241\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1159\/000489241<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\">\n<p><a class=\"es-link found icon-small\" target=\"_blank\" rel=\"noopener\">\u00a0<span class=\"text\">View PDF<\/span>\u00a0<\/a><\/p>\n<div class=\"tooltip-container left\">\n<div class=\"icon\"><\/div>\n<p class=\"message\">This article is free to access.<\/p>\n<\/div>\n<\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85046014150&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref10\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Current%20Mechanistic%20Concepts%20in%20Ischemia%20and%20Reperfusion%20Injury&amp;publication_year=2018&amp;author=M.Y.%20Wu&amp;author=G.T.%20Yiang&amp;author=W.T.%20Liao&amp;author=A.P.%20Tsai&amp;author=Y.L.%20Cheng&amp;author=P.W.%20Cheng&amp;author=C.Y.%20Li&amp;author=C.J.%20Li\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref10\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib11\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib11\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[11]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">X.\u00a0Li,\u00a0N.\u00a0Ma,\u00a0J.\u00a0Xu,\u00a0Y.\u00a0Zhang,\u00a0P.\u00a0Yang,\u00a0X.\u00a0Su,\u00a0Y.\u00a0Xing,\u00a0N.\u00a0An,\u00a0F.\u00a0Yang,\u00a0G.\u00a0Zhang,\u00a0L.\u00a0Zhang,\u00a0Y.\u00a0Xing<\/div>\n<div id=\"ref-id-sbref11\" class=\"title text-m\">Targeting Ferroptosis: Pathological Mechanism and Treatment of Ischemia-Reperfusion Injury<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Oxid. Med Cell Longev.,\u00a02021\u00a0(2021), Article\u00a01587922,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1155\/2021\/1587922\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1155\/2021\/1587922<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\"><a class=\"es-link found-doi icon-small\" target=\"_blank\" rel=\"noopener\"><span class=\"text\">View article<\/span>\u00a0<\/a><\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85118990959&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref11\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Targeting%20Ferroptosis%3A%20Pathological%20Mechanism%20and%20Treatment%20of%20Ischemia-Reperfusion%20Injury&amp;publication_year=2021&amp;author=X.%20Li&amp;author=N.%20Ma&amp;author=J.%20Xu&amp;author=Y.%20Zhang&amp;author=P.%20Yang&amp;author=X.%20Su&amp;author=Y.%20Xing&amp;author=N.%20An&amp;author=F.%20Yang&amp;author=G.%20Zhang&amp;author=L.%20Zhang&amp;author=Y.%20Xing\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref11\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib12\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib12\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[12]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">M.\u00a0Mahjoubin-Tehran,\u00a0S.\u00a0Rezaei,\u00a0A.\u00a0Jesmani,\u00a0N.\u00a0Birang,\u00a0K.\u00a0Morshedi,\u00a0H.\u00a0Khanbabaei,\u00a0H.\u00a0Khan,\u00a0A.\u00a0Piranviseh,\u00a0M.\u00a0Nejati,\u00a0M.\u00a0Aschner,\u00a0H.\u00a0Mirzaei<\/div>\n<div id=\"ref-id-sbref12\" class=\"title text-m\">New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Biomed. Pharm.,\u00a0140\u00a0(2021), Article\u00a0111753,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1016\/j.biopha.2021.111753\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1016\/j.biopha.2021.111753<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\"><a class=\"anchor pdf link anchor-default anchor-icon-left\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332221005357\/pdfft?md5=13a6710773ddbd431c3757f9058711d2&amp;pid=1-s2.0-S0753332221005357-main.pdf\" target=\"_blank\" rel=\"nofollow noopener\" aria-describedby=\"ref-id-sbref12\"><span class=\"anchor-text\">View PDF<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332221005357\" aria-describedby=\"ref-id-sbref12\"><span class=\"anchor-text\">View article<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85108373807&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref12\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=New%20epigenetic%20players%20in%20stroke%20pathogenesis%3A%20From%20non-coding%20RNAs%20to%20exosomal%20non-coding%20RNAs&amp;publication_year=2021&amp;author=M.%20Mahjoubin-Tehran&amp;author=S.%20Rezaei&amp;author=A.%20Jesmani&amp;author=N.%20Birang&amp;author=K.%20Morshedi&amp;author=H.%20Khanbabaei&amp;author=H.%20Khan&amp;author=A.%20Piranviseh&amp;author=M.%20Nejati&amp;author=M.%20Aschner&amp;author=H.%20Mirzaei\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref12\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib13\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib13\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[13]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">K.\u00a0Yang,\u00a0L.\u00a0Zeng,\u00a0A.\u00a0Ge,\u00a0S.\u00a0Wang,\u00a0J.\u00a0Zeng,\u00a0X.\u00a0Yuan,\u00a0Z.\u00a0Mei,\u00a0G.\u00a0Wang,\u00a0J.\u00a0Ge<\/div>\n<div id=\"ref-id-sbref13\" class=\"title text-m\">A systematic review of theresearch progress of non-coding RNAin neuroinflammation and immuneregulation in cerebral infarction\/ischemia-reperfusion injury<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Front. 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Pharm.,\u00a0154\u00a0(2022), Article\u00a0113611,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1016\/j.biopha.2022.113611\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1016\/j.biopha.2022.113611<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\"><a class=\"anchor pdf link anchor-default anchor-icon-left\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222010009\/pdfft?md5=c10c64d3830cfc66d624f7112443f8c0&amp;pid=1-s2.0-S0753332222010009-main.pdf\" target=\"_blank\" rel=\"nofollow noopener\" aria-describedby=\"ref-id-sbref14\"><span class=\"anchor-text\">View PDF<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222010009\" aria-describedby=\"ref-id-sbref14\"><span class=\"anchor-text\">View article<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85137285700&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref14\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=The%20mechanism%20of%20ferroptosis%20regulating%20oxidative%20stress%20in%20ischemic%20stroke%20and%20the%20regulation%20mechanism%20of%20natural%20pharmacological%20active%20components&amp;publication_year=2022&amp;author=K.%20Yang&amp;author=L.%20Zeng&amp;author=X.%20Yuan&amp;author=S.%20Wang&amp;author=A.%20Ge&amp;author=H.%20Xu&amp;author=J.%20Zeng&amp;author=J.%20Ge\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref14\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib15\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib15\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[15]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">P.J.\u00a0Kelly,\u00a0R.\u00a0Lemmens,\u00a0G.\u00a0Tsivgoulis<\/div>\n<div id=\"ref-id-sbref15\" class=\"title text-m\">Inflammation and stroke risk: a new target for prevention<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Stroke,\u00a052\u00a0(8)\u00a0(2021), pp.\u00a02697-2706,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1161\/STROKEAHA.121.034388\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1161\/STROKEAHA.121.034388<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\"><a class=\"es-link found-doi icon-small\" target=\"_blank\" rel=\"noopener\"><span class=\"text\">View article<\/span><\/a><\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85111435034&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref15\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Inflammation%20and%20stroke%20risk%3A%20a%20new%20target%20for%20prevention&amp;publication_year=2021&amp;author=P.J.%20Kelly&amp;author=R.%20Lemmens&amp;author=G.%20Tsivgoulis\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref15\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib16\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib16\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[16]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">D.\u00a0Levard,\u00a0I.\u00a0Buendia,\u00a0A.\u00a0Lanquetin,\u00a0M.\u00a0Glavan,\u00a0D.\u00a0Vivien,\u00a0M.\u00a0Rubio<\/div>\n<div id=\"ref-id-sbref16\" class=\"title text-m\">Filling the gaps on stroke research: Focus on inflammation and immunity<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Brain Behav. 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Pharm.,\u00a0121\u00a0(2020), Article\u00a0109595,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1016\/j.biopha.2019.109595\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1016\/j.biopha.2019.109595<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\"><a class=\"anchor pdf link anchor-default anchor-icon-left\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332219352175\/pdfft?md5=7b9dcf8c8439cdfb441f17e4a6c467fb&amp;pid=1-s2.0-S0753332219352175-main.pdf\" target=\"_blank\" rel=\"nofollow noopener\" aria-describedby=\"ref-id-sbref18\"><span class=\"anchor-text\">View PDF<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332219352175\" aria-describedby=\"ref-id-sbref18\"><span class=\"anchor-text\">View article<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85074467088&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref18\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Pyroptosis%3A%20A%20new%20frontier%20in%20cancer&amp;publication_year=2020&amp;author=Y.%20Fang&amp;author=S.%20Tian&amp;author=Y.%20Pan&amp;author=W.%20Li&amp;author=Q.%20Wang&amp;author=Y.%20Tang&amp;author=T.%20Yu&amp;author=X.%20Wu&amp;author=Y.%20Shi&amp;author=P.%20Ma&amp;author=Y.%20Shu\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref18\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib19\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib19\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[19]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">Y.S.\u00a0Feng,\u00a0Z.X.\u00a0Tan,\u00a0L.Y.\u00a0Wu,\u00a0F.\u00a0Dong,\u00a0F.\u00a0Zhang<\/div>\n<div id=\"ref-id-sbref19\" class=\"title text-m\">The involvement of NLRP3 inflammasome in the treatment of neurodegenerative diseases<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Biomed. 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rel=\"noopener\">\u00a0<span class=\"text\">View PDF<\/span>\u00a0<\/a><\/p>\n<div class=\"tooltip-container left\">\n<div class=\"icon\"><\/div>\n<p class=\"message\">This article is free to access.<\/p>\n<\/div>\n<\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85067309759&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref88\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" 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u-font-sans\">L.\u00a0Galluzzi,\u00a0I.\u00a0Vitale,\u00a0S.A.\u00a0Aaronson,\u00a0J.M.\u00a0Abrams,\u00a0D.\u00a0Adam,\u00a0P.\u00a0Agostinis,\u00a0E.S.\u00a0Alnemri,\u00a0L.\u00a0Altucci,\u00a0I.\u00a0Amelio,\u00a0D.W.\u00a0Andrews,\u00a0M.\u00a0Annicchiarico-Petruzzelli,\u00a0A.V.\u00a0Antonov,\u00a0E.\u00a0Arama,\u00a0E.H.\u00a0Baehrecke,\u00a0N.A.\u00a0Barlev,\u00a0N.G.\u00a0Bazan,\u00a0F.\u00a0Bernassola,\u00a0M.J.M.\u00a0Bertrand,\u00a0K.\u00a0Bianchi,\u00a0M.V.\u00a0Blagosklonny,\u00a0K.\u00a0Blomgren,\u00a0C.\u00a0Borner,\u00a0P.\u00a0Boya,\u00a0C.\u00a0Brenner,\u00a0M.\u00a0Campanella,\u00a0E.\u00a0Candi,\u00a0D.\u00a0Carmona-Gutierrez,\u00a0F.\u00a0Cecconi,\u00a0F.K.\u00a0Chan,\u00a0N.S.\u00a0Chandel,\u00a0E.H.\u00a0Cheng,\u00a0J.E.\u00a0Chipuk,\u00a0J.A.\u00a0Cidlowski,\u00a0A.\u00a0Ciechanover,\u00a0G.M.\u00a0Cohen,\u00a0M.\u00a0Conrad,\u00a0J.R.\u00a0Cubillos-Ruiz,\u00a0P.E.\u00a0Czabotar,\u00a0V.\u00a0D&#8217;Angiolella,\u00a0T.M.\u00a0Dawson,\u00a0V.L.\u00a0Dawson,\u00a0V.\u00a0De Laurenzi,\u00a0R.\u00a0De Maria,\u00a0K.M.\u00a0Debatin,\u00a0R.J.\u00a0DeBerardinis,\u00a0M.\u00a0Deshmukh,\u00a0N.\u00a0Di Daniele,\u00a0F.\u00a0Di Virgilio,\u00a0V.M.\u00a0Dixit,\u00a0S.J.\u00a0Dixon,\u00a0C.S.\u00a0Duckett,\u00a0B.D.\u00a0Dynlacht,\u00a0W.S.\u00a0El-Deiry,\u00a0J.W.\u00a0Elrod,\u00a0G.M.\u00a0Fimia,\u00a0S.\u00a0Fulda,\u00a0A.J.\u00a0Garc\u00eda-S\u00e1ez,\u00a0A.D.\u00a0Garg,\u00a0C.\u00a0Garrido,\u00a0E.\u00a0Gavathiotis,\u00a0P.\u00a0Golstein,\u00a0E.\u00a0Gottlieb,\u00a0D.R.\u00a0Green,\u00a0L.A.\u00a0Greene,\u00a0H.\u00a0Gronemeyer,\u00a0A.\u00a0Gross,\u00a0G.\u00a0Hajnoczky,\u00a0J.M.\u00a0Hardwick,\u00a0I.S.\u00a0Harris,\u00a0M.O.\u00a0Hengartner,\u00a0C.\u00a0Hetz,\u00a0H.\u00a0Ichijo,\u00a0M.\u00a0J\u00e4\u00e4ttel\u00e4,\u00a0B.\u00a0Joseph,\u00a0P.J.\u00a0Jost,\u00a0P.P.\u00a0Juin,\u00a0W.J.\u00a0Kaiser,\u00a0M.\u00a0Karin,\u00a0T.\u00a0Kaufmann,\u00a0O.\u00a0Kepp,\u00a0A.\u00a0Kimchi,\u00a0R.N.\u00a0Kitsis,\u00a0D.J.\u00a0Klionsky,\u00a0R.A.\u00a0Knight,\u00a0S.\u00a0Kumar,\u00a0S.W.\u00a0Lee,\u00a0J.J.\u00a0Lemasters,\u00a0B.\u00a0Levine,\u00a0A.\u00a0Linkermann,\u00a0S.A.\u00a0Lipton,\u00a0R.A.\u00a0Lockshin,\u00a0C.\u00a0L\u00f3pez-Ot\u00edn,\u00a0S.W.\u00a0Lowe,\u00a0T.\u00a0Luedde,\u00a0E.\u00a0Lugli,\u00a0M.\u00a0MacFarlane,\u00a0F.\u00a0Madeo,\u00a0M.\u00a0Malewicz,\u00a0W.\u00a0Malorni,\u00a0G.\u00a0Manic,\u00a0J.C.\u00a0Marine,\u00a0S.J.\u00a0Martin,\u00a0J.C.\u00a0Martinou,\u00a0J.P.\u00a0Medema,\u00a0P.\u00a0Mehlen,\u00a0P.\u00a0Meier,\u00a0S.\u00a0Melino,\u00a0E.A.\u00a0Miao,\u00a0J.D.\u00a0Molkentin,\u00a0U.M.\u00a0Moll,\u00a0C.\u00a0Mu\u00f1oz-Pinedo,\u00a0S.\u00a0Nagata,\u00a0G.\u00a0Nu\u00f1ez,\u00a0A.\u00a0Oberst,\u00a0M.\u00a0Oren,\u00a0M.\u00a0Overholtzer,\u00a0M.\u00a0Pagano,\u00a0T.\u00a0Panaretakis,\u00a0M.\u00a0Pasparakis,\u00a0J.M.\u00a0Penninger,\u00a0D.M.\u00a0Pereira,\u00a0S.\u00a0Pervaiz,\u00a0M.E.\u00a0Peter,\u00a0M.\u00a0Piacentini,\u00a0P.\u00a0Pinton,\u00a0J.H.M.\u00a0Prehn,\u00a0H.\u00a0Puthalakath,\u00a0G.A.\u00a0Rabinovich,\u00a0M.\u00a0Rehm,\u00a0R.\u00a0Rizzuto,\u00a0C.M.P.\u00a0Rodrigues,\u00a0D.C.\u00a0Rubinsztein,\u00a0T.\u00a0Rudel,\u00a0K.M.\u00a0Ryan,\u00a0E.\u00a0Sayan,\u00a0L.\u00a0Scorrano,\u00a0F.\u00a0Shao,\u00a0Y.\u00a0Shi,\u00a0J.\u00a0Silke,\u00a0H.U.\u00a0Simon,\u00a0A.\u00a0Sistigu,\u00a0B.R.\u00a0Stockwell,\u00a0A.\u00a0Strasser,\u00a0G.\u00a0Szabadkai,\u00a0S.W.G.\u00a0Tait,\u00a0D.\u00a0Tang,\u00a0N.\u00a0Tavernarakis,\u00a0A.\u00a0Thorburn,\u00a0Y.\u00a0Tsujimoto,\u00a0B.\u00a0Turk,\u00a0T.\u00a0Vanden 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u-display-inline\">\n<p><a class=\"es-link found icon-small\" target=\"_blank\" rel=\"noopener\">\u00a0<span class=\"text\">View PDF<\/span>\u00a0<\/a><\/p>\n<div class=\"tooltip-container left\">\n<div class=\"icon\"><\/div>\n<p class=\"message\">This article is free to access.<\/p>\n<\/div>\n<\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85036533976&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref92\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" 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href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Astragaloside%20IV%20for%20experimental%20focal%20cerebral%20ischemia%3A%20preclinical%20evidence%20and%20possible%20mechanisms&amp;publication_year=2017&amp;author=H.L.%20Wang&amp;author=Q.H.%20Zhou&amp;author=M.B.%20Xu&amp;author=X.L.%20Zhou&amp;author=G.Q.%20Zheng\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref155\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib157\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib157\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[157]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">H.\u00a0Zhao,\u00a0Y.\u00a0Chen,\u00a0H.\u00a0Feng<\/div>\n<div id=\"ref-id-sbref156\" class=\"title text-m\">P2X7 Receptor-Associated Programmed Cell Death in the Pathophysiology of Hemorrhagic Stroke<\/div>\n<\/div>\n<div class=\"host u-font-sans\">CurrNeuropharmacol,\u00a016\u00a0(9)\u00a0(2018), pp.\u00a01282-1295,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.2174\/1570159X16666180516094500\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.2174\/1570159X16666180516094500<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\"><a class=\"es-link found-doi icon-small\" target=\"_blank\" rel=\"noopener\"><span class=\"text\">View article<\/span><\/a><\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85055080474&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref156\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=P2X7%20Receptor-Associated%20Programmed%20Cell%20Death%20in%20the%20Pathophysiology%20of%20Hemorrhagic%20Stroke&amp;publication_year=2018&amp;author=H.%20Zhao&amp;author=Y.%20Chen&amp;author=H.%20Feng\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref156\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib158\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib158\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[158]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">K.\u00a0Duris,\u00a0Z.\u00a0Splichal,\u00a0M.\u00a0Jurajda<\/div>\n<div id=\"ref-id-sbref157\" class=\"title text-m\">The Role of Inflammatory Response in 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Neuroinflamm.,\u00a017\u00a0(1)\u00a0(2020), p.\u00a0330,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1186\/s12974-020-01988-x\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1186\/s12974-020-01988-x<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\">\n<p><a class=\"es-link found icon-small\" target=\"_blank\" rel=\"noopener\">\u00a0<span class=\"text\">View PDF<\/span>\u00a0<\/a><\/p>\n<div class=\"tooltip-container left\">\n<div class=\"icon\"><\/div>\n<p class=\"message\">This article is free to access.<\/p>\n<\/div>\n<\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85095116758&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref193\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Low-density%20lipoprotein%20receptor%20%20regulates%20NLRP3-mediated%20neuronal%20pyroptosis%20following%20cerebral%20ischemiareperfusion%20injury&amp;publication_year=2020&amp;author=R.%20Sun&amp;author=M.%20Peng&amp;author=P.%20Xu&amp;author=F.%20Huang&amp;author=Y.%20Xie&amp;author=J.%20Li&amp;author=Y.%20Hong&amp;author=H.%20Guo&amp;author=Q.%20Liu&amp;author=W.%20Zhu\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref193\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib195\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib195\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[195]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">Y.\u00a0Wang,\u00a0X.\u00a0Guan,\u00a0C.L.\u00a0Gao,\u00a0W.\u00a0Ruan,\u00a0S.\u00a0Zhao,\u00a0G.\u00a0Kai,\u00a0F.\u00a0Li,\u00a0T.\u00a0Pang<\/div>\n<div id=\"ref-id-sbref194\" class=\"title text-m\">Medioresinol as a novel PGC-1\u03b1 activator prevents pyroptosis of endothelial cells in ischemic stroke through PPAR\u03b1-GOT1 axis<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Pharmacol. Res,\u00a0169\u00a0(2021), Article\u00a0105640,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1016\/j.phrs.2021.105640\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1016\/j.phrs.2021.105640<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\"><a class=\"anchor pdf link anchor-default anchor-icon-left\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1043661821002243\/pdfft?md5=b5a95930caefcb778ec809350ad1bba4&amp;pid=1-s2.0-S1043661821002243-main.pdf\" target=\"_blank\" rel=\"nofollow noopener\" aria-describedby=\"ref-id-sbref194\"><span class=\"anchor-text\">View PDF<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1043661821002243\" aria-describedby=\"ref-id-sbref194\"><span class=\"anchor-text\">View article<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85105056808&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref194\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Medioresinol%20as%20a%20novel%20PGC-1%20activator%20prevents%20pyroptosis%20of%20endothelial%20cells%20in%20ischemic%20stroke%20through%20PPAR-GOT1%20axis&amp;publication_year=2021&amp;author=Y.%20Wang&amp;author=X.%20Guan&amp;author=C.L.%20Gao&amp;author=W.%20Ruan&amp;author=S.%20Zhao&amp;author=G.%20Kai&amp;author=F.%20Li&amp;author=T.%20Pang\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref194\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib196\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib196\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[196]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">X.\u00a0Cao,\u00a0Y.\u00a0Wang,\u00a0L.\u00a0Gao<\/div>\n<div id=\"ref-id-sbref195\" class=\"title text-m\">CHRFAM7A overexpression attenuates cerebral ischemia-reperfusion injury via inhibiting microglia pyroptosis mediated by the NLRP3\/Caspase-1 pathway<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Inflammation,\u00a044\u00a0(3)\u00a0(2021), pp.\u00a01023-1034,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1007\/s10753-020-01398-4\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1007\/s10753-020-01398-4<\/span><\/a><\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\"><a class=\"es-link found-doi icon-small\" target=\"_blank\" rel=\"noopener\"><span class=\"text\">View article<\/span>\u00a0<\/a><\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85099180923&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref195\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=CHRFAM7A%20overexpression%20attenuates%20cerebral%20ischemia-reperfusion%20injury%20via%20inhibiting%20microglia%20pyroptosis%20mediated%20by%20the%20NLRP3Caspase-1%20pathway&amp;publication_year=2021&amp;author=X.%20Cao&amp;author=Y.%20Wang&amp;author=L.%20Gao\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref195\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<li><span class=\"label u-font-sans\"><a id=\"ref-id-bib197\" class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889#bbib197\" data-aa-button=\"sd:product:journal:article:location=references:type=anchor:name=citation-name\"><span class=\"anchor-text\">[197]<\/span><\/a><\/span>\n<div class=\"contribution\">\n<div class=\"authors u-font-sans\">L.L.\u00a0Tan,\u00a0X.L.\u00a0Jiang,\u00a0L.X.\u00a0Xu,\u00a0G.\u00a0Li,\u00a0C.X.\u00a0Feng,\u00a0X.\u00a0Ding,\u00a0B.\u00a0Sun,\u00a0Z.H.\u00a0Qin,\u00a0Z.B.\u00a0Zhang,\u00a0X.\u00a0Feng,\u00a0M.\u00a0Li<\/div>\n<div id=\"ref-id-sbref196\" class=\"title text-m\">TP53-induced glycolysis and apoptosis regulator alleviates hypoxia\/ischemia-induced microglial pyroptosis and ischemic brain damage<\/div>\n<\/div>\n<div class=\"host u-font-sans\">Neural Regen. 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Inflamm.,\u00a02020\u00a0(2020), Article\u00a03201635,\u00a0<a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1155\/2020\/3201635\" target=\"_blank\" rel=\"noreferrer noopener\"><span class=\"anchor-text\">10.1155\/2020\/3201635<\/span><\/a><\/div>\n<div class=\"comment\">PMID: 32454788; PMCID: PMC7238342.<\/div>\n<div class=\"ReferenceLinks u-font-sans\">\n<div class=\"link u-margin-m-right u-display-inline\"><a class=\"es-link found-doi icon-small\" target=\"_blank\" rel=\"noopener\"><span class=\"text\">View article<\/span>\u00a0<\/a><\/div>\n<p><a class=\"anchor link anchor-default\" href=\"https:\/\/www.scopus.com\/inward\/record.url?eid=2-s2.0-85085510204&amp;partnerID=10&amp;rel=R3.0.0\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref256\"><span class=\"anchor-text\">View in Scopus<\/span><\/a><a class=\"anchor link anchor-default\" href=\"https:\/\/scholar.google.com\/scholar_lookup?title=Intravenous%20Arginine%20Administration%20Downregulates%20NLRP3%20inflammasome%20activity%20and%20attenuates%20acute%20kidney%20injury%20in%20mice%20with%20polymicrobial%20sepsis&amp;publication_year=2020&amp;author=S.A.%20Tanuseputero&amp;author=M.T.%20Lin&amp;author=S.L.%20Yeh&amp;author=C.L.%20Yeh\" target=\"_blank\" rel=\"noopener noreferrer\" aria-describedby=\"ref-id-sbref256\"><span class=\"anchor-text\">Google Scholar<\/span><\/a><\/p>\n<\/div>\n<\/li>\n<\/ol>\n<\/section>\n<\/section>\n<div id=\"section-cited-by\">\n<section class=\"ListArticles preview\" aria-label=\"Cited by\">\n<div class=\"PageDivider\"><\/div>\n<header id=\"citing-articles-header\">\n<h2 class=\"u-h4 u-margin-l-ver u-font-serif\">Cited by (7)<\/h2>\n<\/header>\n<div aria-describedby=\"citing-articles-header\">\n<div class=\"citing-articles u-margin-l-bottom\">\n<ul>\n<li class=\"ListArticleItem u-margin-l-bottom\">\n<div class=\"sub-heading u-margin-xs-bottom\">\n<p id=\"citing-articles-article-0-title\" class=\"u-font-serif\"><a class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0378874123009492\"><span class=\"anchor-text\">Bombyx batryticatus extract activates coagulation factor \u216b to promote angiogenesis in rats with cerebral ischemia\/reperfusion injury<\/span><\/a><\/p>\n<div class=\"text-s\">2024, Journal of Ethnopharmacology<\/div>\n<\/div>\n<div class=\"buttons text-s\">\n<p>&nbsp;<\/p>\n<\/div>\n<\/li>\n<li class=\"ListArticleItem u-margin-l-bottom\">\n<div class=\"sub-heading u-margin-xs-bottom\">\n<p id=\"citing-articles-article-1-title\" class=\"u-font-serif\"><a class=\"anchor anchor-default\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0378874123008589\"><span class=\"anchor-text\">Neuroprotective effects of Jie-du-huo-xue decoction on microglia pyroptosis after cerebral ischemia and reperfusion\u2014\u2014From the perspective of glial-vascular unit<\/span><\/a><\/p>\n<div class=\"text-s\">2024, Journal of Ethnopharmacology<\/div>\n<\/div>\n<div class=\"buttons text-s\">\n<p>&nbsp;<\/p>\n<\/div>\n<\/li>\n<li class=\"ListArticleItem u-margin-l-bottom\">\n<div class=\"sub-heading u-margin-xs-bottom\">\n<p id=\"citing-articles-article-2-title\" class=\"u-font-serif\"><a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.21203\/rs.3.rs-3691555\/v1\" target=\"_blank\" rel=\"noopener\"><span class=\"anchor-text\">Machine Learning Analysis of Gene Expression Profiles ofPyroptosis-Related Differentially Expressed Genes in IschemicStroke Revealed Potential Targets for Drug Repurposing<\/span><\/a><\/p>\n<div class=\"text-s\">2023, Research Square<\/div>\n<\/div>\n<div class=\"buttons text-s\"><\/div>\n<\/li>\n<li class=\"ListArticleItem u-margin-l-bottom\">\n<div class=\"sub-heading u-margin-xs-bottom\">\n<p id=\"citing-articles-article-3-title\" class=\"u-font-serif\"><a class=\"anchor anchor-default\" href=\"https:\/\/doi.org\/10.1002\/ptr.7994\" target=\"_blank\" rel=\"noopener\"><span class=\"anchor-text\">Advances of phytotherapy in ischemic stroke targeting PI3K\/Akt signaling<\/span><\/a><\/p>\n<div class=\"text-s\">2023, Phytotherapy Research<\/div>\n<\/div>\n<div class=\"buttons text-s\"><\/div>\n<\/li>\n<\/ul>\n<\/div>\n<p><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0753332222013889\">Source<\/a><\/p>\n<\/div>\n<\/section>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>This suggests that breviscapine may significantly improve the cognitive function of CCI rats and reduce the pathological damage of ischemic neurons, and its mechanism may be related to the inhibition of NLRP3 inflammasome activation and pyroptosis pathway in brain tissue [211].<\/p>\n","protected":false},"author":1,"featured_media":5371,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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