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A combination of astragaloside I, levistilide A and calycosin exerts anti-liver fibrosis effects in vitro and in vivo

Acta Pharmacologica Sinicavolume 39pages14831492 (2018) | Download Citation

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Abstract

Liver fibrosis is excessive accumulation of extracellular matrix proteins that results from various chronic liver diseases. Hepatic stellate cells (HSCs) play an essential role in the pathogenesis of liver fibrosis. Danggui Buxue Tang (DBT) is a classic formula of Chinese traditional medicine. We previously showed that DBT could ameliorate liver fibrosis in rats. However, the bioactive components of DBT in the treatment of liver fibrosis remain unknown. In this study we evaluated 14 ingredients from DBT in human hepatic stellate cell line LX-2, and found that astragaloside I (A), levistilide A (L) and calycosin (C) produced synergistic proliferation inhibition on LX-2 cells and TGF-β1-activated LX-2 cells. Thus, we prepared a mixture of them, and named this combination as ALC formula. Using high-content screening and Western blot assay we revealed that the ALC formula significantly reduced the expression of α-SMA and collagen I in LX-2 cells. The in vivo anti-fibrosis effects of ALC formula were evaluated in a liver fibrosis model in C57BL/6 mice established through injection of dimethylnitrosamine (DMN 2 mg/kg, ip) for 4 weeks. In the third week, the nice were injected with ALC formula (astragaloside I 44.21 mg/kg per day, levistilide A 6 mg/kg per day and calycosin 3.45 mg/kg per day; ip) or sorafenib, a positive control drug (6 mg/kg per day, ip) for 2 weeks. We found that administration of the ALC formula markedly decreased collagen deposition, hydroxyproline (Hyp) content and α-SMA expression levels in the liver tissues compared to the model mice. In conclusion, the present study demonstrates for the first time that astragaloside I, levistilide A and calycosin may be the 3 main bioactive components in DBT; their combination exerts anti-liver fibrosis effects in vitro and in vivo.

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This work was supported by grants from the National Natural Science Foundation of China (No 81402515 and 81473404).

We thank Dr Jing LYU for providing the methods and other helps.

Author information

Affiliations

  1. Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    • Tao Guo
    • , Zu-long Liu
    • , Qiang Zhao
    • , Zhi-min Zhao
    •  & Cheng-hai Liu
  2. Shanghai Clinical Key Laboratory of Traditional Chinese Medicine, Shanghai, 201203, China

    • Zhi-min Zhao
    •  & Cheng-hai Liu
  3. Department of Gastroentology, Hospital No.455 of the PLA, Shanghai, 200052, China

    • Tao Guo

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Correspondence to Zu-long Liu or Cheng-hai Liu.

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DOI

https://doi.org/10.1038/aps.2017.175