Abstract
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.
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Data availability
The MS proteomics and phosphoproteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository (https://www.iprox.cn/) with the dataset identifier PXD039354. Moreover, the source data supporting the findings of this study are available in Supplementary Data 1. All other data generated or analyzed during this study are available from the corresponding author upon reasonable request.
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Acknowledgements
Z.L. discloses support for the research of this work from the National Natural Science Foundation of China [grant numbers 81960701 and 82560765], Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program [grant number CXTD22001] and the National Key R&D Program of China [grant numbers 2019YFC1712302 and 2019YFC1712304]. The remaining authors declare no relevant funding.
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Conceptualization, Z.F.L.; Methodology, D.F.C. and F.Y.; Software, Z.Q.L., Q.W. and Y.L.W.; validation, R.H.C. and Y.M.L.; Formal analysis, R.H.C. and Z.F.L.; Investigation, R.H.C., F.Y., Q.W., Z.Q.L. and Y.M.L.; Resources, Q.W. and D.F.C.; Data curation, Y.L.W., R.H.C. and F.Y.; Writing—original draft preparation, R.H.C. and F.Y.; Supervision, Q.W.; Project administration, Z.F.L. and Y.W.W.; Funding acquisition.
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Feng, Y., Chen, R., Li, Y. et al. Sabinineoside B alleviates metabolic dysfunction-associated steatotic liver disease by targeting PPAR α. Commun Biol (2026). https://doi.org/10.1038/s42003-026-10082-6
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DOI: https://doi.org/10.1038/s42003-026-10082-6
