Chlorogenic acid ameliorated non-alcoholic steatohepatitis via alleviating hepatic inflammation initiated by LPS/TLR4/MyD88 signaling pathway.

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.

• Authors: Xinnan Gu, Mengjuan Wei, Feifei Hu, Hao Ouyang, Zhenlin Huang, Bin Lu, Lili Ji
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 376 Pg. 110461 (May 01 2023) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 36965689 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Lipopolysaccharides
• Myeloid Differentiation Factor 88
• Chlorogenic Acid
• Toll-Like Receptor 4
• NF-kappa B
• Anti-Inflammatory Agents
• Myd88 protein, mouse
• Tlr4 protein, mouse

Topics

• Mice
• Animals
• Non-alcoholic Fatty Liver Disease (pathology)
• Lipopolysaccharides (pharmacology)
• Myeloid Differentiation Factor 88 (metabolism)
• Chlorogenic Acid (pharmacology, therapeutic use)
• Toll-Like Receptor 4 (metabolism)
• Signal Transduction
• Liver (metabolism)
• NF-kappa B (metabolism)
• Inflammation (metabolism)
• Anti-Inflammatory Agents (pharmacology, therapeutic use, metabolism)