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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Danning tablet ameliorates chronic cholestatic liver injury by restoring bile acid homeostasis via an FXR-dependent mechanism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月1日

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  • Weifan Huang,
  • Yanqiu Chen,
  • Chang Yu,
  • Yali Sang,
  • Jiacheng Lin,
  • Yuge Zhou,
  • Fang Wang,
  • Liu Yang,
  • Yu Feng,
  • Xiaoni Kong,
  • Xiaojun Zhu

摘要

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.