Related Experiment Video
Updated: Mar 11, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Multi-target protective effects of Agrimonia pilosa Ledeb. against metabolic dysfunction-associated steatohepatitis
Xinyi Fu1, Jiawen You1, Yunyi Yang1
1Department of Endocrinology, Research Laboratory of Pharmacy, Center of Experimental Animals, Clinical Research Institute of Integrative Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
Agrimonia pilosa Ledeb. (AP), a traditional herbal medicine rich in flavonoids, phenolics, triterpenoids, and glycosides, has been widely used for hepatic injury and metabolic disorders.
Abstract:
This study integrated in vivo and in vitro experiments, UHPLC-HRMS profiling, network pharmacology, and molecular simulation to elucidate the bioactive constituents and mechanisms of AP against metabolic dysfunction-associated steatohepatitis (MASH).
Abstract:
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.
Abstract:
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 cholesterol homeostasis.
Abstract:
These findings demonstrate that AP ameliorates MASH through coordinated regulation of lipid metabolism, inflammatory suppression, and collagen deposition, with AGB representing a promising bioactive candidate warranting further investigation.
