Rutin mitigates hepatic fibrogenesis and inflammation through targeting TLR4 and P2X7 receptor signaling pathway in vitro and in vivo
Rutin mitigates hepatic fibrogenesis and inflammation through targeting TLR4 and P2X7 receptor signaling pathway in vitro and in vivo
复制标题
芦丁在体外和体内通过靶向 TLR4 和 P2X7 受体信号通路减轻肝纤维化和炎症
DOI：
10.1016/j.jff.2019.103700
复制
发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Wu, Yan-Ling
中科院分区：
文献类型：
--
作者：
Hou, Li-Shuang;Cui, Zhen-Yu;Wu, Yan-Ling
芦丁是一种广泛存在于植物中的黄酮醇苷，用作食品抗氧化剂和营养强化剂。大黄具有维生素P样作用和抗炎作用。本研究旨在探讨芦丁在体内外抗肝纤维化的作用及其机制。本研究发现，芸香苷可显著降低活化HSC中的纤维化标志物和TLR 4、IRAK 4、P2 X7 r/NLRP 3信号通路，并具有TLR 4抑制剂的作用。在原代肝细胞中，芦丁还抑制了TGF-β刺激下的TLR 4-IRAK-P2 X7 r信号通路。在TAA诱导的小鼠中，芦丁可以减轻组织病理学变化、纤维化标志物和炎症因子。RxD还抑制TLR、IL-1受体相关激酶、P2 X7 r和NLRP 3的表达。TLR/P2 X7 r信号传导的激活是HSC激活所必需的，有助于小鼠中的肝纤维化。罗格列酮至少部分通过抑制TLR 4和P2 X7 r信号传导而表现出抗肝纤维化的保护作用。
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.