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摘要
Objective To explore the mechanism of Xiaoyaosan in the treatment of metabolic associated fatty liver disease (MAFLD, used to be known as nonalcoholic steatohepatitis, NASH) based on network pharmacology and in vivo experiments. Methods The active components and potential targets of Xiaoyaosan were obtained from TCMSP database, and the disease targets of MAFLD were obtained from Gencards and OMIM database. A protein-protein interaction (PPI) network based on active components and disease common targets was constructed, Metascape platform was used for gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, the "component-target-pathway" network was constructed, and autodock software was used for molecular docking verification of key compounds and targets. MAFLD mouse model was established by feeding methionine and choline deficient L-amino acid diet (MCD). Polyene Phosphatidylcholine Capsules (178 mg·kg?1·d?1) or Xiaoyaosan (1.437, 2.874, 5.748 g·kg?1·d?1) were given to intervene. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG) and total cholesterol (TC) in serum of mice in each group were measured, pathological changes of liver tissues of mice in each group were investigated by HE staining. The protein expressions of PTGS2, ESR1, NOS2 and PPARG were detected by Western blotting. Results 160 active components of Xiaoyaosan and 619 corresponding action targets were obtained, including 133 action targets for the treatment of MAFLD. The core components of Xiaoyaosan in the treatment of MAFLD were quercetin, luteolin, kaempferol and polyporenic acid C and so on, and the key targets were PTGS2, ESR1, NOS2 and PPARG etc. The main biological pathways are tumor related signaling pathways, AGE-RAGE signaling pathways in diabetic complications, IL-17 signaling pathways, and nonalcoholic fatty liver related signal pathways. Molecular docking results show that quercetin, luteolin and kaempferol are strongly associated with PTGS2, ESR1, NOS2 and PPARG. In vivo animal experiments showed that compared with the model group, the levels of AST, ALT, TG and TC in Xiaoyaosan group were significantly reduced (P < 0.05), and the pathological damage of liver tissue was improved. Compared with the model group, the expressions of PTGS2, ESR1 and NOS2 protein in the middle and high dosage groups of Xiaoyaosan were significantly decreased (P < 0.01), while the expression of PPARG protein was significantly increased (P < 0.01). Conclusion Xiaoyaosan may treat MAFLD by regulating targets such as PTGS2, ESR1, NOS2 and PPARG, IL-17 signal pathway and nonalcoholic fatty liver related signal pathway.
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