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San-Cao Granule (三草颗粒) Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway

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Abstract

Objective

To investigate the possible mechanism of San-Cao Granule (SCG, 三草颗粒) mediating antiliver fibrosis.

Methods

A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.

Results

Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).

Conclusion

SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.

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Authors and Affiliations

  1. College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

    Shi-zhang Wei, Jian Wang, Xiao-mei Zhang, Chang Chen, Xiao Ma, Zhe Chen, Zhi-rui Yang & Yan-ling Zhao

  2. Department of Pharmacy, 302 Hospital of People’s Liberation Army, Beijing, 100039, China

    Shi-zhang Wei, Chang Chen, Xiao Ma, Zhe Chen, Zhi-rui Yang & Yan-ling Zhao

  3. Department of Integrative Medical Center, 302 Hospital of People’s Liberation Army, Beijing, 100039, China

    Sheng-qiang Luo, Hong-hong Liu, Jian-yu Li, Rui-lin Wang & Hui-yin Yang

  4. China Military Institute of Chinese Medicine, 302 Hospital of People’s Liberation Army, Beijing, 100039, China

    Jia-bo Wang, Ya-ming Zhang & Xiao-he Xiao

  5. Animal Laboratory Center, 302 Hospital of People’s Liberation Army, Beijing, 100039, China

    Rui-sheng Li

  6. Chongqing Academy of Chinese Traditional Materia Medica, Key Laboratory of Chongqing Traditional Chinese Medicine Resources, Chongqing, 400065, China

    Xiao-mei Zhang & Yan-lei Guo

Authors
  1. Shi-zhang Wei
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  2. Sheng-qiang Luo
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  3. Jian Wang
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  8. Chang Chen
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  9. Xiao Ma
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  10. Zhe Chen
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  11. Hong-hong Liu
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  13. Jian-yu Li
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  15. Ya-ming Zhang
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  16. Hui-yin Yang
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  17. Xiao-he Xiao
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  18. Yan-ling Zhao
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Corresponding author

Correspondence to Yan-ling Zhao.

Additional information

Supported by the Major Projects of the National Science and Technology (No. 2012ZX10005010-002-002) and the National Natural Science Foundation of China (No. 81303120 and No. 81173571)

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Wei, Sz., Luo, Sq., Wang, J. et al. San-Cao Granule (三草颗粒) Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway. Chin. J. Integr. Med. 24, 502–511 (2018). https://doi.org/10.1007/s11655-015-2127-0

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