A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways

• Published in: Journal of microbiology and biotechnology Vol. 32; no. 1; pp. 15 - 26
• Main Authors: Ye, Lin, Xin, Yang, Wu, Zhi-yuan, Sun, Hai-jian, Huang, De-jian, Sun, Zhi-qin
• Format: Journal Article
• Language: Korean
• Published: 한국미생물생명공학회 31.01.2022
• Subjects: 2 2'-azobis(2-amidinopropane) dihydrochloride (AAPH); catechol-O-methyltransferases (COMT); inflammation; Luteolin; catechol-O-methyltransferases (COMT); 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH); Luteolin; inflammation
• ISSN: 1017-7825; 1738-8872

Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.