Author/Authors :
Amirghofran Zahra نويسنده , Rajabi Bazl Masoumeh نويسنده Department of Clinical Biochemistry, Shahid Beheshti University of Medical Sciences, Tehran , Moini Maryam نويسنده Section of Gastroenterology and Hepatology, Department of Internal Medicine, Department of Medi-cine, Shiraz University of Medical Sciences, Shiraz, Iran. , Hosseini Seyed Younes نويسنده Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran , Fattahi Mohammad-Reza نويسنده Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran , KALANTAR Kurosh نويسنده Dept. of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran KALANTAR Kurosh , Shahin Khashayar نويسنده Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, Iran , Ghayour Maryam نويسنده Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, Iran
Abstract :
[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. Real-time polymerase chain reaction (PCR) analysis of the activated cells determined the gene expression levels of important fibrogenic-related molecules.[Results]All components showed significant antiproliferative effects under the therapeutic condition (P < 0.01). Cell growth percentages 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.
