Biomolecules & Therapeutics  
YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages
Hye Jin Oh1,†, Til Bahadur Thapa Magar1,†, Nirmala Tilija Pun1,†, Yunji Lee, Eun Hye Kim1, Eung-Seok Lee1,* and Pil-Hoon Park1,*
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea
E-mail: eslee@yu.ac.kr (Lee ES), parkp@yu.ac.kr (Park PH)
Tel: +82-53-810-2827 (Lee ES), +82-53-810-2826 (Park PH)
Fax: +82-53-810-4654 (Lee ES), +82-53-810-4654 (Park PH)
The first three authors contributed equally to this work.
Received: December 15, 2016; Revised: January 10, 2017; Accepted: January 23, 2017; Published online: April 6, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of reactive oxygen species, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.
Keywords: Chalcone, NADPH oxidase, Reactive oxygen species, p38MAPK, JNK


This Article

e-submission

Archives