Effect of salvianolic acid B on collagen production and mitogen-activated protein kinase activity in rat hepatic stellate cells.
AIM: To investigate the mechanism of salvianolic acid-B (SA-B) action against liver fibrosis relating to mediating hepatic stellate cell (HSC) activation and transforming growth factor-beta1(TGF-beta1) intracellular signal transduction. METHODS: HSC was isolated from normal rat through in situ perfusion of liver with pronase E and density-gradient centrifugation with 11 % nycondenz, then cells were subcultured. Cell proliferation was observed by [3H]TdR uptake. Cellular collagen deposition was measured with Ponceau S stain and semi-quantified with image analytic system. Type I collagen secretion in the supernatant was detected with ELISA. The gene expression of type I pro-collagen was analyzed by RT-PCR. The supernatant was acidified and active TGF-beta1 contents were assayed with ELISA. Mitogen-activated protein kinase ( MAPK) activity was analyzed with immunoprecipitation and Western blot. RESULTS: SA-B 0.1, 1, 10, and 100 micromol/L suppressed HSC proliferation concentration-dependently as determined by [3H]TdR uptake by 94.1 %, 82.4 %, 62.7 %, and 4 % of the control respectively (P<0.05 or P<0.01). SA-B 1, 10, and 100 micromol/L inhibited soluble type I collagen secretion by 75.3 %, 69.8 %, and 63.5 % of the control and decreased the matrix collagen deposition to 86.2 %, 75.4 %, and 73.4 % (P<0.05 or P<0.01). SA-B 1 and 10 micromol/L decreased the cell active TGF-beta1 secretion by 63.3 % and 15.6 % of the control, down-regulated pro-collgen alpha1(I) mRNA expression to 77.0 % and 51.8 % respectively (P<0.05). SA-B 1 and 10 micromol/L also inhibited MAPK activity by 1 to 2 fold respectively. CONCLUSION: SA-B inhibited HSC proliferation and collagen production as well as decreased the cells' TGF-beta1 autocrine and MAPK activity, which might contribute to the mechanism of SA-B action against hepatic fibrosis.[1]References
- Effect of salvianolic acid B on collagen production and mitogen-activated protein kinase activity in rat hepatic stellate cells. Liu, P., Liu, C.H., Wang, H.N., Hu, Y.Y., Liu, C. Acta Pharmacol. Sin. (2002) [Pubmed]
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