Sabinineoside B alleviates metabolic dysfunction-associated steatotic liver disease by targeting PPAR α.

With the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), the development of new drugs targeting this condition is particularly urgent. Sabinineoside B, a new compound of phenanthrene alkaloid glycoside isolated from the traditional Chinese herb Sabia parviflora. Through establishing a high-fat diet mouse model and integrating metabolomics, proteomics, and phosphoproteomics analyses, this study elucidated the efficacy and mechanism of Sabinineoside B in treating MASLD, while preliminarily evaluating its pharmacokinetics and safety. Molecular docking, molecular dynamics simulations, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), pull-down, dual-luciferase reporter gene assays and siRNA techniques were employed to validate the binding interaction between Sabinineoside B and key targets. We found that the Sabinineoside B protein significantly reduces lipid deposition and liver damage in mice on a high-fat diet. Integrated multi-omics analysis and Western blot experiments revealed that Sabinineoside B regulates lipid metabolism and exerts lipid-lowering effects by modulating the PPAR α signaling pathway. Knocking down PPAR α attenuates the regulatory effect of Sabinineoside B on the lipid-lowering pathway, indicating that the molecular mechanism of Sabinineoside B's lipid-lowering activity may be achieved by targeting PPAR α.