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Antifibrotic effects of Salvia miltiorrhiza on dimethylnitrosamine-intoxicated rats

  • Published:
Journal of Biomedical Science

Abstract

Excessive oxidative stress is implicated in hepatic fibrogenesis. Extracts of Salvia miltiorrhiza (Sm) have been shown to protect cells against oxidative stress. In this study we investigated the in vitro and in vivo effects of Sm on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-β1 (TGF-β1). The inhibitory effects of Sm (50~400 μg/ml) on TGF-β1-induced α-smooth muscle actin (α-SMA) secretion and the mRNA expressions of fibrosis-related genes, including α-SMA, connective tissue growth factor (CTGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed. Fibrosis was induced by dimethylnitrosamine (DMN) administration in rats. DMN-treated rats were randomly assigned to 1 of 4 groups: saline, Sm (20 mg/kg), Sm (100 mg/kg), or silymarin (100 mg/kg), each given by gavage twice daily for 5 weeks starting from the onset of DMN administration. Sm (200 and 400 μg/ml) significantly inhibited TGF-β1-stimulated α-SMA secretion and the mRNA expressions of α-SMA, CTGF, and TIMP-1 in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats with either a low (1.8 ± 0.2) or high (1.8 ± 0.1) dose of Sm, or silymarin (1.4 ± 0.2) were significantly reduced in comparison with DMN-treated rats receiving saline (3.1 ± 0.1). Hepatic collagen contents were also significantly reduced by either Sm or silymarin treatment. The mRNA expression levels of α-SMA, TGF-β1, and procollagen I were all attenuated in Sm- and silymarin-treated rats. Moreover, levels of plasma aspartate transaminase activities were reduced by Sm and silymarin treatment. In conclusion, our results show that Sm exerted antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis.

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Abbreviations

ALT:

alanine transaminase

AST:

aspartate transaminase

α-SMA:

α-smooth muscle actin

CCl4:

carbon tetrachloride

CTGF:

connective tissue growth factor

DMN:

dimethylnitrosamine

G3PDH:

glyceraldehyde-3-phosphate dehydrogenase

HSC:

hepatic stellate cell

MMP:

matrix metalloproteinase

ROS:

reactive oxygen species

TGF-β1:

transforming growth factor-β1

TIMP-1:

tissue inhibitor of metalloproteinase-1

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Authors and Affiliations

  1. Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Yi-Chao Hsu, Chang-Yin Lee & Yi-Tsau Huang

  2. National Research Institute of Chinese Medicine, Taipei, Taiwan

    Yun-Lian Lin

  3. Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan

    Yung-Tsung Chiu

  4. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan

    Ming-Shi Shiao

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  1. Yi-Chao Hsu
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  2. Yun-Lian Lin
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  3. Yung-Tsung Chiu
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  4. Ming-Shi Shiao
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  5. Chang-Yin Lee
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  6. Yi-Tsau Huang
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Correspondence to Yi-Tsau Huang.

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Hsu, YC., Lin, YL., Chiu, YT. et al. Antifibrotic effects of Salvia miltiorrhiza on dimethylnitrosamine-intoxicated rats. J Biomed Sci 12, 185–195 (2005). https://doi.org/10.1007/s11373-004-8167-7

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  • DOI: https://doi.org/10.1007/s11373-004-8167-7

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