{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:03:33Z","timestamp":1790003013035,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515010479"],"award-info":[{"award-number":["2024A1515010479"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Science and Technology Program of Guangzhou City","doi-asserted-by":"publisher","award":["2025A04J4282"],"award-info":[{"award-number":["2025A04J4282"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mar. Drugs","Marine Drugs"],"abstract":"<jats:p>Isaridin E (ISE), a marine-derived fungal cyclodepsipeptide, possesses antiplatelet activity in vitro and antithrombotic efficacy in a FeCl3-induced carotid artery thrombosis mouse model without prolonging bleeding time. In this study, we investigated the antiplatelet and neuroprotective effects of prophylactic and therapeutic administration of ISE in a transient middle cerebral artery occlusion (tMCAO) mouse model. We found that both prophylactic administration (50 and 100 mg\/kg) and therapeutic administration (50 mg\/kg) of ISE significantly reduced cerebral infarct volume, alleviated neurological deficits, and attenuated neuronal injury. Furthermore, therapeutic administration of ISE suppressed platelet hyperactivity, as evidenced by reduced P-selectin expression, downregulated platelet secretion-related proteins (SNAP23, VAMP8), and decreased plasma levels of platelet-derived pro-inflammatory cytokines (IL-1\u03b2, PF4, and CCL5). Moreover, ISE attenuated microglial inflammatory activation in the peri-infarct region in vivo. Mechanistically, in vitro studies revealed that this effect may be mediated through the LRP1\/I\u03baB\/NF-\u03baB signaling pathway. In conclusion, these results suggest that ISE protects mice against ischemic stroke by concurrently suppressing platelet hyperactivity and LRP1-associated microglial neuroinflammation.<\/jats:p>","DOI":"10.3390\/md24090328","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:12:09Z","timestamp":1789999929000},"page":"328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isaridin E Attenuates Ischemic Brain Injury in Mice by Concurrently Reducing Platelet Hyperactivity and Microglial Neuroinflammation Associated with LRP1"],"prefix":"10.3390","volume":"24","author":[{"given":"Yu-Chen","family":"Mi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Qi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2765-4015","authenticated-orcid":false,"given":"Lan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Marine Sciences, Sun Yat-sen University, Zhuhai 519082, China"},{"name":"Southern Marine Sciences and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Marine Sciences, Sun Yat-sen University, Zhuhai 519082, China"},{"name":"Southern Marine Sciences and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Clinical College, Guangzhou Medical University, Guangzhou 510261, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-1950","authenticated-orcid":false,"given":"Guan-Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1212\/WNL.0000000000012781","article-title":"Global Epidemiology of Stroke and Access to Acute Ischemic Stroke Interventions","volume":"97","author":"Saini","year":"2021","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e076161","DOI":"10.1136\/bmj-2023-076161","article-title":"Advances in treatments for acute ischemic stroke","volume":"389","author":"Sharma","year":"2025","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41582-022-00703-z","article-title":"The neurovascular unit and systemic biology in stroke\u2014Implications for translation and treatment","volume":"18","author":"Tiedt","year":"2022","journal-title":"Nat. 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