Two novel phenolic glycosides from <i>Saxifraga tangutica</i> for NASH treatment: <i>In vitro</i>, network pharmacology, and molecular docking analysis

Medicinal plants have emerged as valuable inspiration for novel drug discovery owing to their abundant secondary metabolites. This study aimed to further investigate the anti-non-alcoholic steatohepatitis (NASH) potential of secondary metabolites from the traditional Tibetan medicine (TTM) Saxifraga tangutica (S. tangutica). Using medium-pressure liquid chromatography (MPLC) and hydrophilic/reversed–phase liquid chromatography, nine high-purity (&gt;95%) compounds were isolated, including two novel phenolic glycosides: β-D-galactoside-1,6-bis(3,4,5-trihydroxybenzoate) and -(-)-rhododendron-4’-β-D-glucoside. Pharmacological evaluation through Oil Red O staining coupled with comprehensive biochemical profiling demonstrated dose-dependent anti-NASH efficacy of the novel glycosides. Subsequent network pharmacology analysis identified the cAMP and sphingolipid signaling pathways as the principal molecular mechanisms. Molecular docking demonstrated that β-D-galactopyranosyl-1,6-bis(3,4,5-trihydroxybenzoate) exhibited strong binding to HSP90AA1 (-8.65 kcal/mol), and (-)-rhododendrin-4′-β-D-glucopyranoside exhibited strong binding to NFE2L2 (-7.88 kcal/mol). Overall, this study further evaluated the medicinal potential of S. tangutica, while these two novel phenolic glycosides are anticipated to contribute valuable molecular backbones and targeting strategies for NASH drug discovery.