Multi-target protective effects of Agrimonia pilosa Ledeb. against metabolic dysfunction-associated steatohepatitis in mice

作者：Xinyi Fu, Jiawen You, Yi Yang, Shenglan Qi, Shiyu Yang, Xiaoxiao Qu, Yuxin Shao, Ningwei Wang, Zhiying Wang, Yunhao Li, Min Zheng, Hongjie Yang, J. Zhao, X. He, Yanming He · 发表于：Pharmaceutical Biology · 年份：2026 · DOI：10.1080/13880209.2026.2632359 · 研究领域：Liver Disease Diagnosis and Treatment、Natural Antidiabetic Agents Studies、Diet, Metabolism, and Disease

Ledeb. (AP), a traditional herbal medicine rich in flavonoids, phenolics, triterpenoids, and glycosides, has been widely used for hepatic injury and metabolic disorders. experiments, UHPLC-HRMS profiling, network pharmacology, and molecular simulation to elucidate the bioactive constituents and mechanisms of AP against metabolic dysfunction-associated steatohepatitis (MASH). Therapeutic efficacy was evaluated using a MASH mouse model, AML12 hepatocytes, and RAW264.7 macrophages. Active constituents were identified by UHPLC-HRMS, and potential targets were predicted via SwissTargetPrediction and GEO databases, followed by PPI network construction, GO/KEGG enrichment analysis, molecular docking, and molecular dynamics simulation. AP markedly reduced body weight, liver index, and serum AST, ALT, TG, TC, and LDL-c levels, and attenuated hepatic steatosis, inflammation, and fibrosis. In AML12 cells, AP suppressed lipogenesis by downregulating SREBP-1c, FASN, and SCD1, while promoting fatty acid β-oxidation through CPT1A upregulation. In RAW264.7 macrophages, AP inhibited LPS-induced expression of TNF-α, IL-1β, and IL-6. A total of 83 active constituents and 25 key targets were identified, with HMGCR and AXL emerging as hub nodes. Agrimol B (AGB) exhibited favorable binding affinity and structural stability toward both targets. Mechanistically, AGB inhibited HMGCR, reduced SREBP-2 nuclear translocation, and enhanced LXRα/β-mediated cholesterol efflux, maintaining hepatic cholestero...