Insights Into the Mechanism of Action for Qingzhi Decoction for the Treatment of Non‐Alcoholic Fatty Liver Disease via Regulation of the IRS/PI3K/Akt Signaling Pathway and the NRLP3 Inflammasome

The objective of this study is to explore the impacts of Qingzhi Decoction (QZT) in Non-alcoholic fatty liver disease (NAFLD) mice induced by a high-glucose and high-fat diet. UPLC-Orbitrap-Exploris MS characterized 156 bioactive components in QZT. Subsequently, an NAFLD model was established in ICR mice via 8-week feeding with a high-glucose and high-fat diet. The NAFLD mice were randomly divided into four groups. After 8 weeks of drug administration, compared with the control group, the model group showed significant NAFLD-related liver pathological changes, manifested as elevated blood lipid parameters (TC, TG, and LDL) and decreased HDL. Liver injury markers (ALT and AST) and serum inflammatory cytokines (IL-1β, IL-6, and TNF-α) were significantly increased. Molecular analysis indicated that the expression of p-IRs-1, PI3K, and p-Akt was decreased in liver tissue, while the expression of SREBP, NLRP3, caspase1, and GSDMD was increased. QZT treatment alleviated these changes, significantly improving NAFLD pathology, normalizing lipid profiles, and regulating the expression of these molecular markers (p < 0.01). QZT improved insulin resistance, regulated lipid metabolism, and reduced inflammatory response, and its mechanism might be associated with the regulation of IRs-1 and NLRP3 pathways.