ABSTRACT Hepatic ischemia–reperfusion (I/R) injury complicates transplantation, resection, and shock, yet lacks effective pharmacotherapy. We evaluated Leonurine (SCM‐198) as a hepatoprotective agent. Male C57BL/6 mice were pretreated with SCM‐198 for 7 days, then subjected to hepatic I/R and sampled at the reperfusion endpoint. AML12 cells were pretreated with SCM‐198 for 24 h, exposed to hypoxia/reoxygenation (H/R), and immediately analyzed. Injury, inflammation, apoptosis, and cell‐cycle changes were assessed using assay kits, histology, IHC, WB, and qPCR; network pharmacology, docking, and MD simulations explored potential targets. SCM‐198 sharply cut hepatic necrosis and serum transaminases, suppressed pro‐inflammatory cytokines, reduced leukocyte infiltration, blocked apoptosis and restored cyclin D1/cyclin E1. In hypoxia‐reoxygenation AML12 cells, it improved viability, limited oxidative stress and mirrored the anti‐apoptotic effects. Network and dynamic simulation identified stable phosphoinositide 3‐kinase (PI3K) binding, and the compound raised PI3K, protein kinase B and mammalian target of rapamycin phosphorylation; the PI3K inhibitor LY294002 abolished these changes. SCM‐198 protects liver I/R by curbing inflammation, apoptosis, and cell‐cycle arrest via PI3K/AKT/mTOR activation, offering a promising therapeutic candidate.
Wang et al. (Wed,) studied this question.