Rutin mitigates hepatic fibrogenesis and inflammation through targeting TLR4 and P2X7 receptor signaling pathway in vitro and in vivo

Rutin is a flavonol glycoside widely existing in plants, used as food antioxidant and nutritional enhancer. Rutin has vitamin P-like effect and anti-inflammatory effect. This study aims to investigate the effects and potential mechanisms of rutin against hepatic fibrosis in vivo and in vitro. The present study found that rutin significantly decreased fibrosis markers, and TLR4, IRAK4, P2X7r/NLRP3 signaling pathway in activated HSCs, as well as functioning as TLR4 inhibitor. In primary hepatocytes, rutin also inhibited TLR4-IRAK-P2X7r signaling pathway underlying TGF-beta stimulation. In TAA-induced mice, rutin could attenuate the histopathological changes, fibrosis markers, and inflammatory factor. Rutin also suppressed TLRs, IL-1 receptor associated kinase, P2X7r, and NLRP3 expressions. Activation of TLRs/P2X7r signaling is required for HSCs activation, contributing to hepatic fibrosis in mice. Rutin exhibited a protective effect against hepatic fibrosis at least partly through suppressing TLR4 and P2X7r signaling.