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Shenqi pill (SQP), a famous traditional Chinese medicine (TCM) herbal formula derived from Jinguiyaolue (Synopsis of Prescriptions of the Golden Chamber), has long been used to treat kidney yang deficiency syndrome. According to the TCM treatment principle that the liver and kidney are homologies, the clinical use of SQP in the treatment of nonalcoholic steatohepatitis (NASH) has achieved a good effect. However, the active targeted genes and underlying mechanism remain unclear. In this study, we aimed to explore the treatment mechanism of SQP in NASH rats, which may further contribute to the in-depth exploration of SQP in clinical applications. Network pharmacology analysis was used to screen the target genes of SQP for NASH treatment based on public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) analysis were used to search for crucial target genes and mechanisms. UPLC–MS/MS was used to verify the active compounds of the SQP screened. The hepatic pathology and biochemical indicators of rats were used to judge the modeling results and the curative effect of SQP. Western blotting and qRT–PCR were used to verify the expression of crucial target genes at the protein and RNA levels, respectively. Network pharmacology analysis and bioinformatics analysis showed that PTGS2, JUN, MYC, and CDKN1A might be crucial target genes in the primary mechanism of SQP in treating NASH and improving the inflammatory response. The UPLC–MS/MS results confirmed that the hub active compound, quercetin, screened out through the TCMSP database, is indeed present in SQP. Hepatic injury and lipid metabolism indicators of NASH rats were significantly improved after SQP treatment. The results of WB and qRT–PCR showed that the expression of PTGS2, JUN, MYC, and CDKN1A was higher in NASH rats than in normal rats and decreased after SQP treatment. The expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) was reduced after SQP treatment, which confirmed that SQP could improve hepatic inflammation in rats. These results suggested that SQP could ameliorate NASH in rats, and that quercetin may be the critical active compound that exerts the therapeutic effect.

Gut microbiota (GM) dysbiosis and bile acid (BA) metabolism disorder play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Probiotics had a beneficial effect on NAFLD, but further study is needed to explore probiotics as a potential therapeutic agent to NAFLD. The aim of this study was to investigate the regulatory effect of probiotics on gut microbiota in NAFLD rats and to explore the possible mechanism of probiotics regulating the bile acid receptor farnesoid X receptor/growth factor 15 (FXR/FGF15) signaling pathway in rats. We established a rat model of NAFLD fed with a high-fat diet (HFD) for 14 weeks, which was given different interventions (312 mg/kg/day probiotics or 10 mg/kg/day atorvastatin) from the 7th week. Serum lipids and total bile acids (TBA) were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE staining. The expression levels of FXR, FGF15 mRNA, and protein in rat liver were detected. 16S rDNA was used to detect the changes of gut microbiota in rats. Compared with the HFD group, probiotics and atorvastatin significantly reduced serum lipids and TBA levels. And probiotics increased dramatically the expression of FXR, FGF15 mRNA, and protein in the liver. But there were no significant changes in the atorvastatin group. Probiotics and atorvastatin can upregulate the diversity of gut microbiota and downregulate the abundance of pathogenic bacteria in NAFLD model rats. In summary, probiotics alleviated NAFLD in HFD rats via the gut microbiota/FXR/FGF15 signaling pathway.