{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:45:32Z","timestamp":1792842332334,"version":"4.5.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Our study focused on the role of traditional Chinese medicine in stroke therapy, specifically targeting endothelin-1 (ET-1) in astrocytes to alleviate ischemic brain injury. Utilizing oxygen-glucose deprivation\/reoxygenation (OGD\/R) and middle cerebral artery occlusion (MCAO) models, we mimicked cerebral ischemia in both cell cultures and mice. Tetramethylpyrazine (TMP), a component of the Chinese medicine, was identified as a potential therapeutic agent. It significantly increased cell viability, reduced ET-1 expression, and mitigated OGD-induced astrocyte damage, as shown by <jats:italic>in vitro<\/jats:italic> experiments with ET-1 siRNA and cell lines overexpressing ET-1. In the MCAO animal model, TMP improved neurological scores, decreased infarct size, and lowered ET-1 levels, thus strengthening the blood-brain barrier and reducing oxidative stress. TMP\u2019s neuroprotective effects were further linked to the upregulation of phosphorylated AKT (p-AKT), indicating that the AKT pathway may function downstream of ET-1. These results highlight TMP\u2019s potential in treating ischemic stroke by modulating the ET-1 and AKT signaling pathways, offering a promising avenue for future stroke therapies.<\/jats:p>","DOI":"10.3389\/fphar.2025.1571552","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T05:20:08Z","timestamp":1747372808000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Tetramethylpyrazine attenuates the blood-brain barrier damage against ischemic stroke by targeting endothelin-1\/Akt pathway in astrocytes"],"prefix":"10.3389","volume":"16","author":[{"given":"Minzhen","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafeng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqiu","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sookja Kim","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1016\/0092-8674(94)90018-3","article-title":"Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons","volume":"79","author":"Baynash","year":"1994","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1161\/01.str.17.3.472","article-title":"Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination","volume":"17","author":"Bederson","year":"1986","journal-title":"Stroke"},{"key":"B3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/s41572-019-0118-8","article-title":"Ischaemic stroke","volume":"5","author":"Campbell","year":"2019","journal-title":"Nat. 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