Mechanistic evaluation of Jiu Wei Qing Zhi Gao in non-alcoholic fatty liver disease: insights from network Pharmacology and experimental validation.

CONTEXT: Jiu Wei Qing Zhi Gao (JWQZG), a traditional Chinese medicine (TCM) formulation, is widely utilized in China for managing non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: This study aimed to elucidate the therapeutic mechanisms of JWQZG in the management of NAFLD. MATERIALS AND METHODS: Network pharmacology was employed to predict the potential mechanisms of JWQZG in NAFLD management. In vivo experiments were conducted using C57BL/6J mice fed a high-fat diet (HFD) for 16 weeks, followed by treatment with JWQZG at three dosages (1.85, 3.7, and 7.4 g/kg/day) or metformin (150 mg/kg/day) for 8 weeks. In vitro studies utilized HepG2 cells exposed to 0.5 mM palmitic acid (PA) for 24 h to establish an NAFLD model, followed by exposure to JWQZG-containing serum at three concentrations for an additional 24 h. Western blot analysis was used to analyze the expression levels of key signaling pathway components. RESULTS: Results of network pharmacology analysis identified the insulin signaling pathway as a potential mediator of the protective effects of JWQZG in NAFLD. Treatment with JWQZG markedly reduced hepatic steatosis and improved insulin resistance. This was accompanied by enhanced expression of key components in the insulin signaling pathway, including insulin receptor substrate 1 (IRS1), phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT), and phosphorylated GSK3β (p-GSK3β), compared to the NAFLD model group. CONCLUSIONS: These findings provide robust evidence supporting the therapeutic potential of JWQZG in NAFLD and its modulation of the insulin signaling pathway. Furthermore, the study offers valuable insights for the discovery of anti-NAFLD compounds derived from TCM formulations.