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We evaluated Leonurine (SCM\u2010198) as a hepatoprotective agent. Male C57BL\/6 mice were pretreated with SCM\u2010198 for 7\u2009days, then subjected to hepatic I\/R and sampled at the reperfusion endpoint. AML12 cells were pretreated with SCM\u2010198 for 24\u2009h, exposed to hypoxia\/reoxygenation (H\/R), and immediately analyzed. Injury, inflammation, apoptosis, and cell\u2010cycle changes were assessed using assay kits, histology, IHC, WB, and qPCR; network pharmacology, docking, and MD simulations explored potential targets. SCM\u2010198 sharply cut hepatic necrosis and serum transaminases, suppressed pro\u2010inflammatory cytokines, reduced leukocyte infiltration, blocked apoptosis and restored cyclin D1\/cyclin E1. In hypoxia\u2010reoxygenation AML12 cells, it improved viability, limited oxidative stress and mirrored the anti\u2010apoptotic effects. Network and dynamic simulation identified stable phosphoinositide 3\u2010kinase (PI3K) binding, and the compound raised PI3K, protein kinase B and mammalian target of rapamycin phosphorylation; the PI3K inhibitor LY294002 abolished these changes. SCM\u2010198 protects liver I\/R by curbing inflammation, apoptosis, and cell\u2010cycle arrest via PI3K\/AKT\/mTOR activation, offering a promising therapeutic candidate.<\/jats:p>","DOI":"10.1002\/ptr.70244","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T04:34:17Z","timestamp":1770870857000},"page":"2230-2248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leonurine Attenuates Ischemia\u2013Reperfusion Injury Through\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>mTOR<\/scp>\n                    Pathway in Mouse Liver"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5292-4594","authenticated-orcid":false,"given":"Pengru","family":"Wang","sequence":"first","affiliation":[{"name":"Metabolic Hepatobiliary and Pancreatic Diseases Key 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