Journal of Biomedical Science

, Volume 12, Issue 1, pp 185–195 | Cite as

Antifibrotic effects of Salvia miltiorrhiza on dimethylnitrosamine-intoxicated rats

  • Yi-Chao Hsu
  • Yun-Lian  Lin
  • Yung-Tsung Chiu
  • Ming-Shi Shiao
  • Chang-Yin Lee
  • Yi-Tsau  Huang
Article

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.

Keywords

α-smooth muscle actin collagen dimethylnitrosamine hepatic fibrosis Salvia miltiorrhiza transforming growth factor-β1 

Abbreviation

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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Copyright information

© National Science Council, Taipei 2005

Authors and Affiliations

  • Yi-Chao Hsu
    • 1
  • Yun-Lian  Lin
    • 2
  • Yung-Tsung Chiu
    • 3
  • Ming-Shi Shiao
    • 4
  • Chang-Yin Lee
    • 1
  • Yi-Tsau  Huang
    • 1
  1. 1.Institute of Traditional Medicine, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  2. 2.National Research Institute of Chinese MedicineTaipeiTaiwan
  3. 3.Department of Medical Research and EducationTaichung Veterans General HospitalTaichungTaiwan
  4. 4.Department of Medical Research and EducationTaipei Veterans General HospitalTaipeiTaiwan

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