TY - JOUR
T1 - Antifibrotic effects of Salvia miltiorrhiza on dimethylnitrosamine- intoxicated rats
AU - Hsu, Yi Chao
AU - Lin, Yun Lian
AU - Chiu, Yung Tsung
AU - Shiao, Ming Shi
AU - Lee, Chang Yin
AU - Huang, Yi Tsau
PY - 2005/1
Y1 - 2005/1
N2 - 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.
AB - 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.
KW - Collagen
KW - Dimethylnitrosamine
KW - Hepatic fibrosis
KW - Salvia miltiorrhiza
KW - Transforming growth factor-β1
KW - α-smooth muscle actin
UR - http://www.scopus.com/inward/record.url?scp=17744379154&partnerID=8YFLogxK
U2 - 10.1007/s11373-004-8167-7
DO - 10.1007/s11373-004-8167-7
M3 - 文章
C2 - 15864749
AN - SCOPUS:17744379154
SN - 1021-7770
VL - 12
SP - 185
EP - 195
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
IS - 1
ER -
