Gudan Wan reduced liver injury in mouse model of MASH

In a preclinical study using a mouse model of metabolic dysfunction-associated steatohepatitis, the traditional Chinese medicine Gudan Wan reduced hepatic injury, abnormal lipid metabolism, pro-inflammatory cytokine release and fibrosis. Treatment also altered proteins associated with apoptosis and corrected changes in two markers of autophagy, suggesting that the formulation affected several biological processes implicated in the model. The study examined Gudan Wan, a traditional Chinese medicine used for Gu Dan, a syndrome described as involving damp-heat and food stagnation with middle-jiao dysfunction.

The investigators identified analogous pathogenesis between this traditional application and MASH, then used a combination of in vivo toxicity and pharmacodynamic assessments, network pharmacology, western blotting, chemical characterization by UHPLC-QTOF-MS and molecular docking to investigate the formulation’s effects and potential mechanisms. To induce MASH-like changes, researchers fed mice a high-fat diet and administered carbon tetrachloride. Gudan Wan significantly ameliorated liver injury and lipid metabolic disorders in this model and reduced pro-inflammatory cytokine release and fibrosis.

These findings concern an experimentally induced condition in mice; the study did not include people with MASH, and it did not establish whether the treatment would produce the same effects in patients. Network pharmacology identified 237 targets shared by the disease model and Gudan Wan. Within the predicted regulatory network, apoptosis emerged as the central pathway, with CASP3, CASP8, AKT1, TP53, BCL2 and TNF identified as core targets.

Western blotting supported part of this computational model by showing that Gudan Wan increased Bcl-2 and decreased Caspase-3 and Caspase-8, proteins associated with the apoptotic pathway. The same analysis indicated that the formulation corrected autophagic dysfunction, with changes detected in LC3 and p62. Taken together, the biochemical results led the authors to conclude that the observed effects in mice involved both autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis.

The experiments did not independently demonstrate every connection predicted by network pharmacology, and the findings remain specific to the animal model and experimental conditions used. UHPLC-QTOF-MS was used to characterize the chemical composition of Gudan Wan. The analysis identified 179 chemical components, of which 19 were detected in the liver.

Molecular docking predicted favorable binding between major active components and Caspase-3, AKT1, TP53 and TNF-α. By contrast, the major active components were not predicted to bind favorably to Bcl-2 or Caspase-8, suggesting that the formulation might regulate those two proteins indirectly. These docking results are computational predictions rather than experimental confirmation of direct binding or target engagement.

Safety was assessed in a separate 30-day toxicity test. The researchers reported no overt toxicity or organic lesions in mice receiving Gudan Wan at doses up to 4,000 milligrams per kilogram. This observation applies to the tested mice, formulation, exposure period and dose range; it does not establish human safety, tolerability or a therapeutic dose in people.

Overall, the study provides experimental and computational evidence that Gudan Wan can influence liver injury, inflammation, fibrosis, autophagy and apoptosis-related proteins in a mouse model of MASH. Its favorable toxicity finding in mice supports further preclinical investigation, but the research does not demonstrate clinical efficacy in humans. The conclusions also do not extend beyond the formulation, doses, treatment period and induced disease model evaluated in the study.

Subject of Research: Preclinical evaluation of Gudan Wan in a mouse model of metabolic dysfunction-associated steatohepatitis

Article Title: Gudan Wan attenuates metabolic dysfunction-associated steatohepatitis by modulating autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis

Article References: Han, S., Li, Q., Ding, Z., Yang, H., Du, D., Zhou, Q., Yu, J., & Yang, X. (2026). Gudan Wan attenuates metabolic dysfunction-associated steatohepatitis by modulating autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis. Frontiers in Cell and Developmental Biology, 14, Article 1993264. https://doi.org/10.3389/fcell.2026.1993264

Image Credits: AI Generated

DOI: 10.3389/fcell.2026.1993264

Keywords: Gudan Wan, MASH, mouse model, liver injury, liver fibrosis, autophagy, apoptosis, traditional Chinese medicine, network pharmacology, molecular docking, Gudan, attenuates