Chlorogenic acid ameliorated non-alcoholic steatohepatitis via alleviating hepatic inflammation initiated by LPS/TLR4/MyD88 signaling pathway. (1st May 2023)

• Record Type: Journal Article
• Authors: Gu, Xinnan; Wei, Mengjuan; Hu, Feifei; Ouyang, Hao; Huang, Zhenlin; Lu, Bin; Ji, Lili
• Is Part Of: Chemico-biological interactions. Volume 376(2023)
• Publication Date: 2023-05-01
• Subjects: NASH -- CGA -- Hepatic inflammation -- MyD88 -- NFκB -- Inflammasome; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2023.110461
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: CGA alleviated NASH in mice fed with MCDD. CGA reduced liver steatosis and oxidative injury via activating PPARα and Nrf2. CGA alleviated liver inflammation via blocking NFκB and inflammasome activation. CGA inhibited the activation of macrophages induced by LPS. CGA blocked LPS-TLR4-MyD88 signaling cascade in macrophages via binding to MyD88.