Background: Non-alcohol fatty liver disease (NAFLD) is the most prevalent hepatopathy in China, with few effective cures currently. This work aimed to confirm the effect of DHM in vivo/vitro and explore the potential mechanism based on a network pharmacology-based approach.
Methods: The rats were fed using a high-fat diet (HFD) to accumulate lipid. DHM at different concentrations was used to treat the HFD rats. The serum total cholesterol (TC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected using ELISA kits. The target genes of DHM against NAFLD were screened by online databases. Then, the cytotoxicity of DHM in primary hepatocytes and HepG2 cells was determined by MTT reagent. qRT-PCR was used to quantify the expression level of PPAGR and CASP3 mRNA. Cell apoptosis and intracellular triglyceride (TG) were detected.
Results: HFD diet increased rat liver weight/body weight ratio, serum TC, ALT, and AST. But DHM treatment can reduce these elevated indicators. DHM targeted 14 potential genes in NAFLD. PPARG and CASP3 were two hub genes for DHM against NAFLD, with score factor coefficients of -7.1 and -6.8 kcal/mol. DHM reduced the increased PPARG mRNA level and intracellular TG induced by palmitic acid. DHM can reduce the increased CASP3 mRNA level and cell apoptosis induced by palmitic acid.
Conclusion: This work demonstrates a mechanism of DHM that alleviates lipid metabolism disorder and cell apoptosis for the treatment of NAFLD, evidencing the potential application of DHM in NAFLD.
Keywords: CASP3; Dihydromyricetin; Non-alcohol fatty liver disease; PPARG.
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