In vitro study of flavonoids, fatty acids, and steroids on proliferation of rat hepatic stellate cells

There is a wealth of evidence that hepatic stellate cells (HSCs) orchestrate most of the important events in liver fibrogenesis. After liver injury, HSCs become activated to a profibrogenic myofibroblastic phenotype and can regulate net deposition of collagens and other matrix proteins in the liver. The proliferation of HSCs is mainly stimulated by the platelet-derived growth factor (PDGF). In this study, some compounds from natural resources have been tested for their activity to inhibit PDGF-driven proliferative activity of rat HSCs. Apigenin, quercetin, genistein, daidzin, and biochanin A exhibited > 75% inhibitory activity against HSC-T6. It was found that, gamma-linolenic (gamma-Ln), eicosapentanoic (EPA) and a- linolenic (alpha-Ln) acids showed a high inhibitory effect on proliferation of rat HSCs at 50 nmol/1. Cholest-4-ene-3,6-dione and stigmastone-4-en-3,6-dione are the most active steroids with inhibitory activities > 80% and this is most likely due to the presence of the 4-en-3,6-dione moiety in both compounds. These results revealed that the compounds which effectively blocked HSC proliferation may be beneficial in liver fibrosis. Structure-activity relationships (SAR) may provide a basis for rational structure modification.