基于AMPK/PI3K/AKT通路探讨清开灵口服液治疗NAFLD的作用机制OA

Non-alcoholic fatty liver disease(NAFLD)is the most prevalent and worlwide chronic liver disease.Due to the complex pathogenesis and lacking targeted therapies,it is critically significant to explore intervention strategies.In this study,we first established lipid accumulation models to evaluate the efficacy of Qingkailing Oral Liquid(QKL)in alleviating NAFLD-associated lipid accumulation.Network pharmacology was employed to screen potential therapeutic targets,followed by validation of key signaling pathway genes and proteins expression via qPCR and Western blot.The results showed that:① After 48 h of treatment withφ=0.5％,1％,2％QKL,both HepG2 and AML-12 lipid accumulation models exhibited a significant reduction in lipid droplet size and number.The triglyceride(TG)content decreased in a dose-dependent manner,with φ=2％QKL showing comparable efficacy to 2 mmol/L metformin.Network pharmacology predicted that key pathways,including phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)and adenosine monophosphate-activated protein kinase(AMPK),play crucial roles in QKL-mediated intervention.Molecular docking suggested potential binding activity between QKL and targets such as AMPK and PI3K.② QKL likely exerts its anti-lipid accumulation effects through dual regulation of the AMPK-SREBP1 and PI3K-AKT-mTOR signaling pathways,thereby effectively mitigating hepatic lipid deposition.③ This study employed an integrated"in vitro modeling-network pharmacology-experimental validation"strategy to systematically investigate the molecular mechanisms by which QKL modulates lipid metabolism in NAFLD,providing novel insights for both modernization of traditional Chinese medicine and the development of therapeutic strategies against NAFLD.