Effects of silibinin and of a synthetic analogue on isolated rat hepatic stellate cells and myofibroblasts.

Hepatic stellate cells and the derived myofibroblasts play a central pathogenic role in liver fibrogenesis. In order to identify the still unknown hepatoprotective properties of the flavonoid silibinin and the related pyridylchromone NH40 x HCl (2-(3-pyridyl)-4-H-1-benzopyran-4-one hydrochloride), their effects on isolated rat hepatic stellate cells and derived myofibroblasts were determined. Concentrations of 10(-4) mol/l silibinin reduced the proliferation of freshly isolated rat hepatic stellate cells by about 75%, but had no detectable effect on their viability, morphology and their cytoskeletal architecture. It reduced the transformation towards myofibroblasts and down-regulated the gene expression of extracellular matrix components and the profibrogenic transforming growth beta. Whereas silibinin concentrations higher than 10(-4) mol/l were toxic, lower concentrations had no effects on the proliferation and transformation behavior. Although 10(-4) mol/l NH40 x HCl reduced the proliferation rate by about 50%, this substance had no significant effect on the transformation process. The results indicate that one important aspect of the potential antifibrotic properties of silibinin might be the inhibition of hepatic stellate cell proliferation and transformation.