الفهرس 
Potential antifibrotic effects of some natural compounds against experimental hepatic fibrogenesis
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Abstract
Liver fibrosis is one of the leading causes of morbidity/mortality worldwide; where hepatic stellate cells (HSCs) activation is a key step in liver fibrogenesis. So far, no effective pharmaceutical intervention for the treatment of liver fibrosis is available; thereby interest has increased in the biological activities offered by natural products, as polyphenols. Despite the well-known biological activities of polyphenolics mainly flavonoids including rutin and hydroxyl safflower A (HSYA) as well as phenolic acids including rosmarinic acid (RA) and gallic acid (GA), their exact antifibrotic mechanisms remain unidentified. Hence, the current study aimed to investigate their efficacies against hepatic fibrogenesis as well as their possible mechanism of actions. The in vitro studies were performed on stellate cell line (HSC-T6) whereas liver fibrosis was established in rats via chronic thioacetamide (TAA)-intoxication. Rats were divided into (i) normal, (ii) TAA-intoxicated rats; TAA-intoxicated rats treated with (iii) silymarin, (iv) rutin, (v) RA, (vi) HSYA or (vii) GA. All treatments were administered daily for 8 weeks via oral gavage. Levels of ALT, AST, albumin, platelet derived growth factor-BB (PDGF-BB), tissue inhibitor of matrix metalloproteinases type-1(TIMP-1), hydroxyproline and expression of proliferating cellular nuclear antigen (PCNA) together with histopathological examinations of hepatic tissues. Their impact on transforming growth factor (TGF)-Ý1 levels, expressions of Ü-smooth muscle actin (Ü-SMA) and caspase-3 were measured in vitro and in vivo. Results revealed that rutin, RA and GA exhibited significant antiproliferative effects on HSC-T6 (IC50 at 48 h= 460, 171 and 19 og/ml, respectively). RA and GA exhibited differential morphological effects on HSCs where some cells were disintegrated while others retained back their quiescent morphology