Danning tablet ameliorates chronic cholestatic liver injury by restoring bile acid homeostasis via an FXR-dependent mechanism.
5 affiliations
- 1Central Laboratory, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China.
- 2Shanghai Innovative Engineering Technology Research Center for Traditional Chinese Medicine Solid Preparations, Shanghai, China.
- 3Pudong New Area Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. [email protected].
- 4Central Laboratory, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. [email protected].
- 5Department of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. [email protected].
Abstract
Background
Chronic cholestatic liver injury (CLI) is a progressive condition with limited therapeutic options. This study aimed to evaluate the efficacy and underlying mechanism of Danning Tablet (DNT), a traditional Chinese medicine, in treating chronic CLI.Methods
We established murine models of intrahepatic and extrahepatic cholestasis using a 3,5-diethoxycarbonyl-1,4-dihydropyridine (DDC) diet and bile duct ligation (BDL), respectively. The effects of oral DNT on liver injury, inflammation, ductular reaction, and fibrosis were systematically evaluated. Transcriptomics and the use of the Farnesoid X Receptor (FXR) inhibitor Guggulsterone were employed to elucidate the mechanism of action.Results
In both DDC and BDL models, DNT treatment significantly reduced serum markers of liver injury (ALT, AST, TBIL, TBA). DNT also markedly attenuated hepatic inflammation, ductular proliferation, and fibrosis. Mechanistically, DNT restored bile acid homeostasis by activating the FXR signaling pathway, leading to the upregulation of the transporter BSEP and downregulation of the synthesis enzyme CYP7A1. Crucially, the therapeutic benefits of DNT were abrogated by co-administration with the FXR inhibitor, confirming its FXR-dependent action.Conclusions
DNT effectively alleviates chronic cholestatic liver injury by activating the FXR pathway, which restores bile acid homeostasis and subsequently mitigates inflammation and fibrosis. This study provides a strong preclinical rationale for the clinical use of DNT as a promising FXR-dependent therapy for chronic cholestatic liver diseases.
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BibTeX
@article{huang2026danning,
title = {{Danning tablet ameliorates chronic cholestatic liver injury by restoring bile acid homeostasis via an FXR-dependent mechanism.}},
author = {Weifan Huang and Yanqiu Chen and Chang Yu and Yali Sang and Jiacheng Lin and Yuge Zhou and Fang Wang and Liu Yang and Yu Feng and Xiaoni Kong and Xiaojun Zhu},
journal = {BMC complementary medicine and therapies},
year = {2026},
month = aug,
doi = {10.1186/s12906-026-05497-x},
url = {https://europepmc.org/article/MED/42958218},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Danning tablet ameliorates chronic cholestatic liver injury by restoring bile acid homeostasis via an FXR-dependent mechanism.
AU - Weifan Huang
AU - Yanqiu Chen
AU - Chang Yu
AU - Yali Sang
AU - Jiacheng Lin
AU - Yuge Zhou
AU - Fang Wang
AU - Liu Yang
AU - Yu Feng
AU - Xiaoni Kong
AU - Xiaojun Zhu
PY - 2026
DA - 2026/08/01
JO - BMC complementary medicine and therapies
DO - 10.1186/s12906-026-05497-x
UR - https://europepmc.org/article/MED/42958218
AB - Background Chronic cholestatic liver injury (CLI) is a progressive condition with limited therapeutic options. This study aimed to evaluate the efficacy and underlying mechanism of Danning Tablet (DNT), a traditional Chinese medicine, in treating chronic CLI.Methods We established murine models of intrahepatic and extrahepatic cholestasis using a 3,5-diethoxycarbonyl-1,4-dihydropyridine (DDC) diet and bile duct ligation (BDL), respectively. The effects of oral DNT on liver injury, inflammation, ductular reaction, and fibrosis were systematically evaluated. Transcriptomics and the use of the Farnesoid X Receptor (FXR) inhibitor Guggulsterone were employed to elucidate the mechanism of action.Results In both DDC and BDL models, DNT treatment significantly reduced serum markers of liver injury (ALT, AST, TBIL, TBA). DNT also markedly attenuated hepatic inflammation, ductular proliferation, and fibrosis. Mechanistically, DNT restored bile acid homeostasis by activating the FXR signaling pathway, leading to the upregulation of the transporter BSEP and downregulation of the synthesis enzyme CYP7A1. Crucially, the therapeutic benefits of DNT were abrogated by co-administration with the FXR inhibitor, confirming its FXR-dependent action.Conclusions DNT effectively alleviates chronic cholestatic liver injury by activating the FXR pathway, which restores bile acid homeostasis and subsequently mitigates inflammation and fibrosis. This study provides a strong preclinical rationale for the clinical use of DNT as a promising FXR-dependent therapy for chronic cholestatic liver diseases.
SN - 2662-7671
ER -