Alcoholic liver disease (ALD) is a prevalent and progressive hepatic disorder driven by chronic excessive alcohol consumption. Leonurine (LH), a bioactive alkaloid isolated from Herba Leonuri, possesses well-documented antioxidant and cytoprotective properties. This study comprehensively investigated the hepatoprotective efficacy of LH against ethanol-induced liver injury and mechanistically dissected its molecular underpinnings. Antioxidant capacity and cytoprotective activity were assessed in ethanol-treated hepatocytes. Network pharmacology and gene expression analysis were performed to identify potential therapeutic targets and signaling pathways. UHPLC–MS/MS-based metabolomics was applied to characterize endogenous metabolic alterations induced by LH. LH demonstrated significant antioxidant activity and was predicted to interact with 44 ALD-related targets. Functional enrichment and gene validation analyses revealed that its protective effects were primarily associated with regulation of the JAK2–STAT3 signaling pathway. Metabolomic profiling identified 48 differential metabolites and 25 significantly affected metabolic pathways. Integrated analysis of metabolites and target genes further supported the JAK–STAT signaling pathway as a central regulatory axis, which was confirmed in cellular experiments. Collectively, these results demonstrate that LH confers hepatoprotection in ALD primarily through modulation of the JAK2–STAT3 signaling pathway, underscoring its translational promise as a mechanism-informed therapeutic candidate.
Xiao et al. (Thu,) studied this question.