{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:18:29Z","timestamp":1788268709727,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1448700"],"award-info":[{"award-number":["23ZR1448700"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ginsenoside Rg1 has shown promise in ameliorating cerebral ischemia\u2013reperfusion injury (CIRI). However, its precise molecular mechanisms remain unclear. In this study, an in\u00a0vitro CIRI model was established using SH\u2010SY5Y and SK\u2010N\u2010AS neuronal cell lines subjected to oxygen\u2013glucose deprivation followed by reoxygenation (OGD\/R). For the in\u00a0vivo model, C57BL\/6J mice underwent middle cerebral artery occlusion and subsequent reperfusion (MCAO\/R). The protective effects of Rg1 against OGD\/R injury were analysed using the CCK\u20108 assay and the PI exclusion method. The in\u00a0vivo neuroprotective effects of Rg1 against CIRI were evaluated using various assessments, including brain blood flow, neurological deficits, behavioural tests, TTC, H&amp;E, Nissl and TUNEL staining. Mitophagy was assessed by detecting mitophagy\u2010initiating proteins via Western blotting, transmission electron microscopy, immunohistochemistry and immunofluorescence staining. Additionally, mitochondrial function was assessed by ATP measurement, the JC\u20101 assay and MitoSOX\u2010based flow cytometry. Our results show that Rg1 significantly mitigated cell death caused by OGD\/R and substantially enhanced cell viability in\u00a0vitro. Moreover, Rg1 alleviated OGD\/R\u2010induced mitochondrial dysfunction, as indicated by preserved mitochondrial membrane potential and decreased mitochondrial ROS levels. Mitophagy was induced after OGD treatment, which was subsequently inhibited by Rg1 during reperfusion. Mechanistically, Rg1 disrupted the fusion of mitophagosomes with lysosomes rather than inhibiting mitophagy initiation, leading to an accumulation of mitochondrial proteins and mitophagy\u2010initiating proteins. Notably, prolonged inhibition of mitophagy by Rg1 did not induce cytotoxicity or exacerbate mitochondrial dysfunction. Furthermore, administration of Rg1 in MCAO\/R mice significantly improved brain blood reperfusion, reduced infarct volume, improved neurological deficits, preserved brain tissue integrity and decreased neuronal apoptosis. Consistent with the in\u00a0vitro observations, Rg1 upregulated mitophagy\u2010related protein expression in MCAO\/R mouse brain tissues, indicating potential inhibition of mitophagy. In conclusion, our study reveals that Rg1 significantly alleviates CIRI at least partially by suppressing mitophagy, specifically by impeding the fusion of mitophagosomes with lysosomes.<\/jats:p>","DOI":"10.1111\/cpr.70071","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T04:06:04Z","timestamp":1748923564000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Neuroprotective Role of Ginsenoside Rg1 Against Cerebral Ischemia\u2013Reperfusion Damage Through Inhibition of Mitophagy via Blocking Mitophagosome\u2010Lysosome Fusion"],"prefix":"10.1111","volume":"59","author":[{"given":"Lin","family":"Ai","sequence":"first","affiliation":[{"name":"Department of Neurology Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine  Shanghai 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