Yinchenhao Decoction ameliorates high-fat diet-induced lipid metabolism disorder

ABSTRACT:

In this study, a HFD-induced lipid metabolism disorder model was established in C57BL/6 mice in vivo, and a palmitic acid (PA)-induced hepatocyte lipid accumulation model was constructed in HepG2 cells in vitro. Using component identification, network pharmacology, transcriptome sequencing, molecular docking, and in vivo and in vitro molecular biological verification, we systematically screened the core active components of YCHD and elucidated its regulatory mechanism via the P53/STAT3-CIDEC signaling pathway. In vivo animal experiments showed that YCHD significantly inhibited abnormal weight gain, improved glucose tolerance and insulin resistance, and reduced total cholesterol (TC) and triglyceride (TG) levels in serum and liver tissues of HFD-fed mice. HE staining and Oil Red O staining confirmed that YCHD markedly alleviated hepatocyte steatosis and lipid deposition without obvious toxicity to major organs, indicating favorable safety. UPLC-MS/MS qualitatively and quantitatively analyzed the components of YCHD. A component-disease-target network was constructed, and combined with PPI and transcriptomic analysis, epiberberine, emodin, and magnoflorine were identified as core active components, with P53 and STAT3 as key targets. Transcriptome sequencing identified numerous differentially expressed genes related to lipid metabolism and inflammation, among which CIDEC was significantly altered. Further enrichment analysis and literature review verified that P53/STAT3 was enriched in lipid metabolism and inflammatory signaling pathways. Western blotting indicated that P53/STAT3 might regulate lipid metabolism disorders by modulating CIDEC expression. YCHD significantly downregulated the phosphorylation of P53 and STAT3 and inhibited the abnormal expression of CIDEC, verifying its ameliorative effect on HFD-induced lipid metabolism disorders. In vitro cell experiments demonstrated that epiberberine, emodin, and magnoflorine effectively reduced TC and TG levels and lipid accumulation in PA-treated HepG2 cells at safe concentrations. Western blotting and qPCR confirmed that all three components downregulated the phosphorylation of P53 and STAT3 and suppressed CIDEC expression. Molecular docking revealed strong binding activity between the three components and STAT3, verifying the targeted interaction at the molecular level. In conclusion, this study identifies epiberberine, emodin, and magnoflorine as the core active components of YCHD against lipid metabolism disorders. YCHD exerts its therapeutic effects by inhibiting the phosphorylation of P53 and STAT3, downregulating CIDEC expression, and reducing hepatocyte lipid accumulation, thereby alleviating HFD-induced obesity, insulin resistance, and hepatic steatosis. This study reveals the multi-component and multi-target mechanism of YCHD at animal, cellular, and molecular levels, providing experimental and theoretical support for the modern interpretation, clinical application, and development of natural lipid-lowering agents of classic TCM formulas. Limitations include insufficient exploration of the synergistic compatibility of the three components and the use of only HepG2 cells in vitro. Future studies can employ primary hepatocytes and gene knockout models to further clarify upstream/downstream regulation and the gut-liver axis mechanism. 

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14689 | MetaboLights | 2027-06-26

REPOSITORIES: MetaboLights