Abstract:
Despite rutin, extracted from black mulberry, has several pharmacological activities, its exact effect against hepatic fibrosis remains incompletely identified. Accordingly, this study investigates whether rutin is a promising candidate for treating hepatic fibrosis and to clarify its underlying antifibrotic mechanisms in vitro and in vivo. In vitro studies were performed on hepatic 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 or (iv) rutin. Levels of ALT, AST, platelet-derived growth factor-BB (PDGF-BB), tissue inhibitor metalloproteinases type-1 (TIMP-1), hydroxyproline and expression of proliferating cellular nuclear antigen (PCNA) together with histological changes were examined. Activities of rutin on TGF-β1, α-smooth muscle actin (α-SMA) and caspase-3 were measured in vitro and in vivo. Rutin exhibited no marked HSC-T6 cell death (IC50 = 460 µg.ml−1), however, it showed reduction in HSCs activation (low TGF-β1 level and α-SMA positive cells) and induced apoptosis (high caspase-3 positive cells). Rutin also ameliorated liver functions, reduced hepatic levels of PDGF-BB, TGF-β1, TIMP-1, hydroxyproline and restored PCNA, together with attenuation in fibrosis score (S1 vs S4). Rutin could be a promising candidate for treating hepatic fibrosis through down-regulation of HSCs activation and induction of apoptosis. © 2021 Taylor & Francis Group, LLC.
