脂肪性肝炎
炎症
TLR4型
脂肪肝
脂肪变性
炎症体
内分泌学
内科学
化学
药理学
医学
癌症研究
疾病
作者
Xiangyu Gu,Mengjuan Wei,Feifei Hu,Hao Ouyang,Zhenlin Huang,Bin Lü,Lili Ji
标识
DOI:10.1016/j.cbi.2023.110461
摘要
Non-alcoholic steatohepatitis (NASH) is a severe pathological stage in non-alcoholic fatty liver disease (NAFLD) and is generally recognized to be induced by chronic inflammation. Natural compound chlorogenic acid (CGA) is well-known for its anti-inflammatory capacity. This study aimed at evaluating the alleviation of CGA on NASH and further exploring its engaged mechanism via focusing on abrogating hepatic inflammation. Our results showed that CGA had a good amelioration on NASH in vivo. CGA alleviated liver oxidative injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) activation and reduced liver steatosis via up-regulating peroxisome proliferator-activated receptor-alpha (PPARα). CGA attenuated hepatic inflammation in vivo, but didn't decrease the elevated lipopolysaccharide (LPS) content. CGA blocked the activation of nuclear factor kappa-B (NFκB) or inflammasome both in MCDD-fed mice and in LPS-stimulated macrophages. CGA was found to directly bind to myeloid differentiation primary response 88 (MyD88), and thus competitively blocked the interaction between toll-like receptor 4 (TLR4) and MyD88, thereby abrogating hepatic inflammation initiated by LPS-TLR4-MyD88. Moreover, the CGA-provided anti-inflammatory effect was obviously disappeared in macrophages overexpressed MyD88. Hence, CGA has an excellent efficacy in improving NASH. CGA alleviated liver inflammation during NASH progression through blocking LPS-TLR4-MyD88 signaling pathway via directly binding to MyD88.
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