Objective To investigate the hypolipidemic effects of gypenosides based on serum, liver and fecal metabolomics techniques. Methods A high-fat diet was used to establish a hyperlipidemia model in rats, with 32 male SD rats randomly divided into control group, model group, atorvastatin (10 mg/kg) group and gypenosides (150 mg/kg) group. After eight weeks of continuous administration, body weight and blood lipid levels were measured. Metabolites in serum, liver and feces were analyzed using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, and differential metabolites were screened through multivariate statistical analysis. Results Gypenosides significantly reduced levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in serum of hyperlipidemic rats (P < 0.05, 0.01). Metabolomics analysis revealed that gypenosides effectively normalized the endogenous metabolic profile of model rats, identifying 30, 27, 19 differential metabolites in serum, liver and feces, respectively, primarily including lysophosphatidylcholine, unsaturated fatty acids and derivatives, bile acids, and amino acids and derivatives, linked to glycerophospholipid, linoleic/arachidonic acid, unsaturated fatty acid, primary bile acid biosynthesis, and tryptophan metabolism. Except for glycoursodeoxycholic acid and glycylglycoursodeoxycholic acid in liver, which still showed an increasing trend after gypenosides intervention, all other differential metabolites returned to near-normal levels. Conclusion Gypenosides modulate blood lipids by regulating the lipid metabolism network through multiple targets, with mechanisms related to intervention in lysophosphatidylcholine metabolism, linoleic acid and arachidonic acid metabolism, bile acid metabolism and tryptophan metabolism pathways, systematically revealing the overall regulatory effect of gypenosides on endogenous metabolism of hyperlipidemic rats.

gypenosides  /  hypolipidemic  /  metabolomics  /  lysophosphatidylcholine  /  bile acids  /  gypenoside A