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
2021; Springer Science+Business Media; Volume: 32; Issue: 1 Linguagem: Inglês
10.4014/jmb.2104.04027
ISSN1738-8872
AutoresLin Ye, Xin Yang, Zhiyuan Wu, Hai‐Jian Sun, Dejian Huang, Zhi-Qin Sun,
Tópico(s)Bioactive natural compounds
ResumoLuteolin 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 COMTcatalyzed 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 LPSstimulated 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.
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