{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:10:25Z","timestamp":1788307825400,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T00:00:00Z","timestamp":1724457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen)\u00a0on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2\u2009weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3\u03b2 in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3\u03b2\/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF\u2010\u03b1 and IL\u201023 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen\u2010treated, Th17 differentiation\u2010inducing cell\u2010conditioned medium significantly up\u2010regulated the expression of tight junction proteins ZO\u20101, Occludin, and Claudin\u20105 in murine aortic endothelial cells. Administering the GSK3\u03b2 inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up\u2010regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3\u03b2, which reduces endothelial cell injury and up\u2010regulates tight junction protein expression.<\/jats:p>","DOI":"10.1002\/ptr.8320","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T08:54:37Z","timestamp":1724489677000},"page":"5184-5202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Geniposide modulates <scp>GSK3\u03b2<\/scp> to inhibit Th17 differentiation and mitigate endothelial damage in intracranial aneurysm"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-2819","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u2010Feng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run\u2010Dong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Health Science and Engineering University of Shanghai for Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u2010He","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sir Run Run Shaw Hospital (Shaoxing)  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-472X","authenticated-orcid":false,"given":"Yi\u2010Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-1405","authenticated-orcid":false,"given":"Peng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,24]]},"reference":[{"key":"e_1_2_11_2_1","article-title":"Isolation and th17 differentiation of na\u00efve CD4 T lymphocytes","volume":"79","author":"Bedoya S. 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