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Volume 42 Issue 5
May  2026
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Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(5): 1083-1092

Regulatory effect of astragaloside Ⅰ and calycosin on a mouse model of cholestatic liver fibrosis

DOI: 10.12449/JCH260513
  • 1.

    Institute of Liver Diseases，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China

  • 2.

    Key Laboratory of Liver and Kidney Diseases Ministry of Education/Shanghai Key Laboratory of Traditional Chinese Clinical Medicine，Shanghai 201203，China

  • 3.

    Department of Pharmacy，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine/Grade 3 Laboratory of Traditional Chinese Medicine Preparation，State Administration of Traditional Chinese Medicine，Shanghai 201203，China

  • 4.

    Institute of Interdisciplinary Integrative Medicine Research，Shanghai University of Traditional Chinese Medicine/Shanghai Frontier Science Center of TCM Chemical Biology，Shanghai 201203，China

Research funding:

Shanghai Science and Technology Committee Rising-Star Program (24QA2709200);

Shanghai Oriental Talent Program Youth Project (QNWS2024054);

Shanghai Natural Science Foundation (24ZR1467100);

Shanghai Natural Science Foundation (25ZR1401335);

Major and Difficult Diseases Integrated Traditional Chinese and Western Medicine Clinical Collaboration Project (ZDYN-2024-A-075);

Shanghai Three-Year Action Plan for Further Accelerating the Inheritance, Innovation and Development of Traditional Chinese Medicine[ZY（2025-2027）-3-1-1] 

More Information
  • Corresponding author: LIU Ping， liuliver@vip.sina.com （ORCID： 0000-0002-6152-4508）; LI Chunhui， lchtcm@163.com （ORCID： 0009-0002-0534-3101）
  • Received Date: 2025-12-04
  • Accepted Date: 2026-01-21
  • Published Date: 2026-05-25
    Abstract
  •   Objective  To identify and validate the optimal compatibility dosage of astragaloside Ⅰ （ASⅠ） and calycosin （CY） in the treatment of cholestatic liver fibrosis.  Methods  A 3，5-diethoxycarbonyl-1，4-dihydrocollidine （DDC） diet was used to establish a mouse model of liver fibrosis， and the uniform design method was used to identify the optimal combination ratio of the saponin component ASⅠ and the flavonoid component CY in Astragalus membranaceus. In the uniform design experiment， 80 male C57/BL6J mice were divided into normal group， model group， total astragalosides （TAS） group， groups A — F with a uniform design， and obeticholic acid （OCA） group using a random number table， with 8 mice in each group. The multiple regression analysis was used to establish the optimal regression equation and obtain the potential optimal combination ratio. The in vivo efficacy of the empirically optimal combination identified in the uniform design and the optimal dose combination predicted by the regression equation were compared for validation. A one-way analysis of variance was used for comparison of continuous data between multiple groups； the Levene test was used to determine the homogeneity of variance， and the least significant difference t-test was used for comparison of data with homogeneity of variance between two groups， while the Dunnett T3 test was used for comparison of data with heterogeneity of variance.  Results  In the uniform design regimen， the JYB combination （3.125 mg/kg ASI+50 mg/kg CY） significantly reduced the serum levels of alanine aminotransferase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， total bilirubin （TBil）， and indirect bilirubin （IBil） in mice with DDC-induced cholestatic liver fibrosis （all P<0.05）， and it also reduced hepatic Hyp content （P<0.01）， semi-quantified collagen deposition area （P<0.001）， and the mRNA expression levels of Acta2， Col1a1， Ck7， Ck19， Adgre1， TLR4， TNF-α， and CCL5 in liver tissue （all P<0.05）. The regression equation showed that 50 mg/kg ASⅠ+50 mg/kg CY was the potential optimal combination， which was named as P1 combination. However， subsequent validation experiments showed that P1 combination only significantly improved the serum levels of AST and IBil and hepatic Hyp content in DDC mice （all P<0.05）， with no significant impact on hepatic collagen deposition and the mRNA expression levels of Acta2， Ck7， Ck19， Adgre1， and CCL5 （all P>0.05）. In contrast， the JYB combination significantly improved the serum levels of ALP， ALT， AST， TBA， TBil， and IBil， hepatic collagen deposition， hepatic Hyp content， and the mRNA expression levels of Acta2， Col1a1， Ck7， Ck19， Adgre1， TLR4， TNF-α， and CCL5 （all P<0.05）.  Conclusion  This study shows that the JYB combination （3.125 mg/kg ASⅠ+50 mg/kg CY） can significantly alleviate DDC-induced liver fibrosis， with comparable efficacy to total saponins from Astragalus membranaceus， and compared with ASⅠ or CY administered alone， the JYB combination has a significantly better regulatory effect on the serum levels of ALP and TBA.

     

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