Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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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

  • Ye, Lin (School of Pharmacy, Changzhou University) ;
  • Xin, Yang (Food Science and Technology Program, Department of Chemistry, Faculty of Science, National University of Singapore) ;
  • Wu, Zhi-yuan (Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Sun, Hai-jian (Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Huang, De-jian (Food Science and Technology Program, Department of Chemistry, Faculty of Science, National University of Singapore) ;
  • Sun, Zhi-qin (Changzhou Second People's Hospital)
  • Received : 2021.04.20
  • Accepted : 2021.05.25
  • Published : 2022.01.28
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Abstract

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.

Keywords

Acknowledgement

This work was supported by the Science and Technology Project of Changzhou City (Grant No. CE20215028).

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