Gudan Wan attenuates metabolic dysfunction-associated steatohepatitis by modulating autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis
- 1The First Clinical College, Yunnan University of Chinese Medicine, Kunming, China
- 2College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming, China
- 3Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, Kunming, China
Abstract
Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading global cause of end-stage liver disease, with safe and effective therapies still lacking. Gudan Wan (GDW), a traditional Chinese medicine for Gu Dan (damp-heat and food stagnation with middle-jiao dysfunction), shares analogous pathogenesis with MASH, yet its anti-MASH efficacy remains to be elucidated.
Methods: GDW’s therapeutic efficacy and underlying mechanisms via in vivo toxicity and pharmacodynamic evaluation, network pharmacology, western blotting, UHPLC-Q-TOF-MS characterization, and molecular docking. A MASH model of mice was induced by high-fat diet and carbon tetrachloride (HFD+CCl4).
Results: A 30-day toxicity test revealed no overt toxicity or organic lesions in mice at GDW doses up to 4000 mg/kg. MASH mice, GDW significantly ameliorated hepatic injury, lipid metabolic disorders, pro-inflammatory cytokine release, and fibrosis. Network pharmacology identified 237 intersecting targets, with apoptosis as the core regulatory pathway and CASP 3/8, AKT1, TP53, BCL2, and TNF as core targets. Western blotting confirmed GDW modulated key apoptotic proteins (upregulating Bcl-2, downregulating Caspase-3/8) and corrected autophagic dysfunction via LC3 and p62 modulation. A total of 179 chemical components were characterized by UHPLC-QTOF-MS, of which 19 were found to enter the liver. Molecular docking predicted favorable binding of the major active components to Caspase-3, AKT1, TP53, and TNF-α, but not to Bcl-2 or Caspase-8, suggesting indirect regulation of the latter two by GDW.
Conclusion: GDW exerts its anti-MASH effects by modulating autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis, with its favorable safety profile supporting its therapeutic potential for further investigation.
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BibTeX
@article{han2026gudan,
title = {{Gudan Wan attenuates metabolic dysfunction-associated steatohepatitis by modulating autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis}},
author = {Shaocong Han and Qiuyi Li and Zhongneng Ding and Huan Yang and Di Du and Qidi Zhou and Jie Yu and Xingxin Yang},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1993264},
url = {https://doi.org/10.3389/fcell.2026.1993264},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gudan Wan attenuates metabolic dysfunction-associated steatohepatitis by modulating autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis
AU - Shaocong Han
AU - Qiuyi Li
AU - Zhongneng Ding
AU - Huan Yang
AU - Di Du
AU - Qidi Zhou
AU - Jie Yu
AU - Xingxin Yang
PY - 2026
DA - 2026/10/22
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1993264
UR - https://doi.org/10.3389/fcell.2026.1993264
AB - Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading global cause of end-stage liver disease, with safe and effective therapies still lacking. Gudan Wan (GDW), a traditional Chinese medicine for Gu Dan (damp-heat and food stagnation with middle-jiao dysfunction), shares analogous pathogenesis with MASH, yet its anti-MASH efficacy remains to be elucidated. Methods: GDW’s therapeutic efficacy and underlying mechanisms via in vivo toxicity and pharmacodynamic evaluation, network pharmacology, western blotting, UHPLC-Q-TOF-MS characterization, and molecular docking. A MASH model of mice was induced by high-fat diet and carbon tetrachloride (HFD+CCl4). Results: A 30-day toxicity test revealed no overt toxicity or organic lesions in mice at GDW doses up to 4000 mg/kg. MASH mice, GDW significantly ameliorated hepatic injury, lipid metabolic disorders, pro-inflammatory cytokine release, and fibrosis. Network pharmacology identified 237 intersecting targets, with apoptosis as the core regulatory pathway and CASP 3/8, AKT1, TP53, BCL2, and TNF as core targets. Western blotting confirmed GDW modulated key apoptotic proteins (upregulating Bcl-2, downregulating Caspase-3/8) and corrected autophagic dysfunction via LC3 and p62 modulation. A total of 179 chemical components were characterized by UHPLC-QTOF-MS, of which 19 were found to enter the liver. Molecular docking predicted favorable binding of the major active components to Caspase-3, AKT1, TP53, and TNF-α, but not to Bcl-2 or Caspase-8, suggesting indirect regulation of the latter two by GDW. Conclusion: GDW exerts its anti-MASH effects by modulating autophagy and the Bcl-2/Caspase-3/Caspase-8 apoptotic axis, with its favorable safety profile supporting its therapeutic potential for further investigation.
SN - 2296-634X
ER -