[Mechanism of Sini Power combined with Linggui Zhugan Decoction on NAFLD based on transcriptomics and metabolomics]

This study aims to evaluate the potential of Sini Power combined with Linggui Zhugan Decoction(SLD) in alleviating non-alcoholic fatty liver disease(NAFLD) and explore its mechanisms. A NAFLD model was constructed via high-fat diet(HFD) feeding for male Sprague-Dawley rats, followed by oral gavage administration of SLD for two weeks. Comprehensive evaluations included serum biochemical analysis, enzyme-linked immunosorbent assay(ELISA), and hepatic histopathological examination. Transcriptomics and metabolomics were employed to analyze the potential mechanisms, with the protein expression validated by Western blot(WB) technique. Animal experiments showed that SLD exerted hepatoprotective effects by improving liver function, inhibiting inflammatory response, and reducing hepatic cell injury. Metabolomics analysis identified 28 differential metabolites, involving metabolic pathways such as vitamin B6, thiamine, nicotinic acid/nicotinamide, and aldonic acid metabolism. The transcriptomics study indicated that SLD significantly regulated the expression of 189 genes, involving biological processes such as fatty acid biosynthesis, butanoic acid metabolism, caffeine metabolism, and eukaryotic ribosome biogenesis. Additionally, SLD regulated key signaling pathways including peroxisome proliferator-activated receptor(PPAR), tumor protein P53(P53), and Hippo. Further studies revealed that SLD activated the PPAR signaling pathway by upregulating key targets such as peroxisome proliferator-activated receptor δ(PPARδ) and fatty acid desaturase 2(FADS2) and downregulating Acyl-CoA synthetase long chain family member 3(ACSL3) and 3-hydroxy-3-methylglutaryl-CoA synthase 1(HMGCS1), which promoted fatty acid β-oxidation, inhibited fatty acid synthesis, improved hepatic lipid metabolism, and ultimately exerted the effects of protecting liver function and alleviating liver injury.