OBJECTIVE To explore the mechanism of Huangjing pills(HP) alleviating metabolic associated fatty liver disease(MAFLD).

METHODS The key components, core targets and main pathways of HP against MAFLD were screened by network pharmacology. A model of hepatic steatosis in L-02 cells were induced by 5% medical fat emulsion and treated with HP. MAFLD rat models were induced by high fat diet-feeding and administered HP. Changes in fat accumulation, cell damage and energy metabolism were evaluated in liver L-02 cells. Changes in body weight, food intake, histological parameters, organ indexes, biochemical parameters and mitochondrial indicators involved in ultrastructure, oxidative stress and energy metabolism were investigated.

RESULTS A total of seventeen active ingredients of HP were obtained through network pharmacological screening, which might act on 62 MAFLD-involved targets and mainly related to certain signaling pathways such as PI3K/AKT and AGE-RAGE. The cell experiments showed that HP decreased the levels of total cholesterol(TC), triglyceride(TG), alanine transaminase(ALT), alanine transaminase(AST), phospho-nuclear factor kappa B, phospho-protein kinase B, phospho-phosphatidylinositol-3-kinase and tumor necrosis factor-α(TNF-α), and increased the levels of ATP synthase, glutathione(GSH) and superoxide dismutase(SOD). Animal experiments showed that HP decreased the levels of TC, TG, low density lipoprotein cholesterol, ALT, AST, interleukin-1β, interleukin-6, TNF-α and malondialdehyde(MDA), and increased the levels of high density lipoproteincholesterol, ATP synthase and GSH. Additionally, HP protected the damage of liver mitochondria, inhibited the increase of MDA and the decrease of SOD, GSH, ATP synthase, ComplexⅠ and Complex Ⅱ in liver mitochondria.

CONCLUSION HP alleviate MAFLD by inhibiting the PI3K/AKT signaling pathway and mitochondrial oxidative stress injury, which provides a new strategy for the prevention and treatment of MAFLD.