comparison of the in vitro antifibrogenic effects of silymarin, silybin a and 18α-glycyrrhizin on activated hepatic stellate cells

Background: hepatic stellate cells (hscs), the most important cells in liver fibrogenesis, are a major target of the fibrosis therapy. objectives: this study aimed to compare the anti-fibrogenic effects of three natural components, including silymarin, silybin a and 18α-glycyrrhizin on an activated lx-2 hsc line under prophylactic and therapeutic conditions. methods: we treated hscs with silymarin, silybin a and 18α-glycyrrhizin before (prophylactic) and after (therapeutic) activation by tgf-β1, and then we measured their antiproliferative effects by the mtt assay. the level of released tgf-β1 was measured. realtime polymerase chain reaction (pcr) analysis of the activated cells determined the gene expression levels of important fibrogenicrelated molecules. results: all components showed significant antiproliferative effects under the therapeutic condition (p < 0.01). cell growth per- centages inhibited by the 25 µg/ml concentrations of these products were 63.9 ± 4.7% (silymarin), 76.8 ± 1.6% (silybin a) and 86.8 ± 15.2% (18α-glycyrrhizin). in the prophylactic application, only silybin a had significant antiproliferative effects (85.1 ± 3.1%, p < 0.05). silybin a had the highest reduction in tgf-β1 release in both conditions (p < 0.001). in real-time pcr, therapeutic treatment of cells with silybin a and 18α-glycirrhizin had greater impacts compared to silymarin in decreasing collagen type i-alpha-1 (colia1), tissue inhibitor of metalloproteinase (timp)-1 and matrix metalloproteinase (mmp)-2 mrna levels. in contrast, under prophylactic conditions silymarin reduced all fibrogenic genes. silybin a did not affect colia1 and 18α-glycyrrhizin had no effect on colia1 and timp-1. conclusions: the antifibrogenic effects of silybin a and 18α-glycyrrhizin were stronger in the therapeutic compared to the prophylactic experiment. silymarin had a greater inhibitory effect on fibrogenic gene expressions under the prophylactic condition.