Studies on the protective effect of total flavonoids from Cichorium glandulosum roots against carbon tetrachloride-induced liver fibrosis in rats

Purpose: To study the protective influence of total flavonoids from Cichorium glandulosum roots (TFCG) against carbon tetrachloride-mediated hepatic fibrosis in rats, and the probable mechanism of action involved. Methods: Rats with liver fibrosis were orally administered TFCG (50, 100 or 200 mg/kg) once a day for 13 weeks. Liver index and liver injury indices in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), lactate dehydrogenase (LDH), y-glutamyl transpeptidase (y-GT), hydroxyproline (HYP), albumin (ALB) and malondialdehyde (MDA) were determined using electronic balance or corresponding assay kits, as appropriate. Following staining with hematoxylin and eosin and Van Gieson, histopathological changes in liver tissues were examined by light microscopy. TGF-beta/Smad pathway-related protein expressions in liver tissues, viz, transforming growth factor-beta 1 (TGF-beta 1), mothers against decapentaplegic homolog 3 (Smad3), Smad7, toll-like receptor 4 (TLR4) and a-smooth muscle actin (alpha-SMA) were determined using immunohistochemical techniques. Results: Exposure to TFCG significantly reversed abnormal serum levels of ALT, AST, AKP, LDH, gamma-GT, HYP, ALB and MDA rats with liver fibrosis to normal levels, and also decreased their liver index values (p < 0.01). Moreover, TFCG improved histopathological changes in the liver tissues of fibrotic rats, and significantly reversed abnormal TGF-beta 1, Smad3, Smad7, TLR4 and alpha-SMA protein expressions in the liver tissues of fibrotic rats to normal levels (p < 0.05 or 0.01). Conclusion: These results indicate that TFCG exerts protective effect against fiver fibrosis via a mechanism related to inactivation of TGF-beta/Smad pathway. Thus, TFCG may find application in liver fibrosis therapy.