Nonalcoholic fatty liver disease (
NAFLD) is a clinicopathological syndrome of abnormal
lipid deposition in the liver mediated by nonalcohol intake. The Gexia Zhuyu decoction, a classic
traditional Chinese medicine compound, is widely used in the clinical treatment of
NAFLD. However, its specific efficacy and underlying mechanisms have not been elucidated yet. This study aimed to quantitatively evaluate the efficacy of the Gexia Zhuyu decoction using pharmacodynamics and to explore its molecular mechanisms in conjunction with proteomics. High-fat diets and
methionine choline-deficient diets were used to induce various
NAFLD progression stages in mouse models. The effects of oral Gexia Zhuyu decoction administration on
NAFLD were evaluated by measuring the serum and liver indicators of the treated mice before and after drug intervention and by comparing the changes in liver tissue. Liver TRPM4
mRNA and
protein levels were measured using reverse transcription-polymerase chain reaction and Western blotting, respectively. Experimental data showed that serum ALT, AST, and liver
triglyceride (TG) levels in each disease stage group of drug intervention mice decreased, and
high-density lipoprotein (HDL) and
superoxide dismutase (SOD) levels increased. Liver TG levels decreased after drug intervention in the
liver fibrosis mice, but serum TG levels increased. Furthermore, cellular fatty changes, inflammatory changes, and fibrous tissue proliferation were all relieved. The TRPM4
protein and
mRNA levels in the liver tissue were decreased, and the
microRNA (miRNA)-24 expression was increased. The Gexia Zhuyu decoction has a clear
therapeutic effect at each stage of
NAFLD. It likely acts by altering miRNA-24 expression and regulating the target TRPM4
protein pathway to achieve
NAFLD treatment.