Monosaccharide and Disaccharide Saponins of Shade‐Dried <i>Gynostemma Pentaphyllum</i> Confer Metabolic Benefits in Mice With Non‐Alcoholic Fatty Liver Disease

Gynostemma pentaphyllum (Thunb.), a traditional medicinal plant, is processed through different methods such as roller drying and shade drying. Shade-dried G. pentaphyllum (SDGPs) contained monosaccharide and disaccharide saponins, while roller-dried G. pentaphyllum (RDGPs) contained trisaccharide and tetrasaccharide saponins. These methods may affect its bioactive compounds, but their influence on non-alcoholic fatty liver disease (NAFLD) remains unclear. This study aims to compare the anti-NAFLD effects of G. pentaphyllum processed by these two methods and identify the active ingredients involved. Saponin fractions and monomers from both processing methods were isolated using chromatography. A mouse model of NAFLD was induced by a high-fat and cholesterol diet to assess the therapeutic effects of the fractions. Molecular docking, surface plasmon resonance, and transcription analysis were used to evaluate the interactions of saponins with the Farnesoid X receptor (FXR). SDGPs exhibited better therapeutic effects on NAFLD in mice, with monosaccharide saponins being more effective than trisaccharide saponins. Gypenoside TN-1 outperformed Gypenoside XLVI in treating the NAFLD phenotype. Molecular analysis revealed a stronger binding affinity of monosaccharide saponins to FXR. SDGPs, especially the monosaccharide saponins, provide greater therapeutic benefits in treating NAFLD, likely through activation of the FXR-FGF15 signaling pathway. These findings suggest that shade drying may be a more effective method for enhancing the therapeutic potential of G. pentaphyllum for NAFLD treatment.