Sophoricoside inhibits hepatic ischemia-reperfusion injury by promoting AMPK activation

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Author: LI Xinyan ¹ ZHANG Yonghui ² DONG Xinran ² ZHANG Xiaojing ²  LI Kun ¹

Affiliation: 1. Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China 2. School of Pharmaceutical Sciences, Gannan Medical University, Gannan Innovation and Translational Medicine Research Institute, State Key Laboratory of New Drug Target Discovery and New Drug Creation for Major Diseases, Ganzhou 341000, Jiangxi province, China

Keywords: Hepatic ischemia-reperfusion injury Sophoricoside AMP-activated protein kinase Inflammation Apoptosis

DOI: 10.12173/j.issn.1005-0698.202508075

Reference: LI Xinyan, ZHANG Yonghui, DONG Xinran, ZHANG Xiaojing, LI Kun. Sophoricoside inhibits hepatic ischemia-reperfusion injury by promoting AMPK activation[J]. Yaowu Liuxingbingxue Zazhi, 2025, 34(12): 1399-1412. DOI: 10.12173/j.issn.1005-0698.202508075.[Article in Chinese]  Copied

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Abstract

Objective To investigate the protective effect of the natural compound sophoricoside (SOP) against hepatic ischemia-reperfusion injury (HIRI) and its underlying molecular mechanism, providing evidence for the development of HIRI therapeutics.

Methods An in vitro hypoxia/reoxygenation (H/R) model in hepatocytes and an in vivo mouse hepatic ischemia-reperfusion injury (HIRI) model were established. In vitro, cell viability was assessed by CCK-8 assay, while inflammatory cytokines and related proteins were analyzed using RT-qPCR and Western blot (WB). In mice, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured. Hepatic pathological damage and apoptosis were evaluated by H&E staining and immunofluorescence staining. Molecular docking predicted the interaction between SOP and AMP-activated protein kinase (AMPK), which was then validated using the AMPK inhibitor Compound C.

Results SOP significantly enhanced hepatocyte viability and suppressed inflammatory cytokine production under H/R conditions in vitro. In mice, SOP reduced serum ALT and AST levels, alleviated hepatic inflammation, and decreased apoptosis. Mechanistic studies indicated that, SOP promoted AMPK phosphorylation in both in vitro and in vivo. Molecular docking indicated stable binding of SOP to AMPK through hydrogen bonding. The protective effects of SOP were reversed by AMPK inhibition, confirming AMPK as a critical target of SOP action.

Conclusion SOP exerts a protective effect against HIRI by targeting and activating AMPK to inhibit inflammation and apoptosis, providing a new strategy for natural product-based drug development and targeted therapy for HIRI

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