Rutin mitigates hepatic fibrogenesis and inflammation through targeting TLR4 and P2X7 receptor signaling pathway in vitro and in vivo. (January 2020)

• Record Type: Journal Article
• Authors: Hou, Li-Shuang; Cui, Zhen-Yu; Sun, Peng; Piao, Hui-Qing; Han, Xin; Song, Jian; Wang, Ge; Zheng, Shuang; Dong, Xiu-Xiu; Gao, Lu; Zhu, Yue; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling
• Is Part Of: Journal of functional foods. Volume 64(2020)
• Publication Date: 2020-01
• Subjects: Rutin -- Hepatic fibrosis -- Inflammation -- TLRs -- P2X7r; HSCs hepatic stellate cells -- TGF-β transforming growth factor β -- ECM extracellular matrix -- TAA thioacetamide -- P2X7r P2X7 receptor -- α-SMA α smooth muscle actin -- MMP13 matrix metalloproteinase 13 -- TIMP-1 tissue inhibitors of metalloproteinases-1 -- TLR4 toll like receptor 4 -- NLRP3 NLR family pyrin domain containing 3 -- PAMPs pathogen-associated molecular patterns -- DAMPs damage-associated molecular patterns -- TRAF TNF receptor-associated factor -- ASC apoptosis-associated speck-like protein containing a CARD -- caspase-1 cysteinyl aspartate specific proteinase-1 -- LPS lipopolysaccharide -- IRF3 interferon regulatory Factor 3 -- TNF-α tumor necrosis factor α -- MyD88 myeloid differentiation factor 88; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2019.103700
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Rutin mitigates hepatic fibrogenesis via TLR4-P2X7r signaling. Rutin decreases fibrosis markers in activated HSCs via suppressing TLR4. Rutin protects primary hepatocytes via blocking TLR4-P2X7r. Abstract: 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-β 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.