YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages.
10.4062/biomolther.2016.276
- Author:
Hye Jin OH
1
;
Til Bahadur Thapa MAGAR
;
Nirmala Tilija PUN
;
Yunji LEE
;
Eun Hye KIM
;
Eung Seok LEE
;
Pil Hoon PARK
Author Information
1. College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea. eslee@yu.ac.kr
- Publication Type:Original Article
- Keywords:
Chalcone;
NADPH oxidase;
Reactive oxygen species;
p38MAPK;
JNK
- MeSH:
Chalcone;
Down-Regulation;
Macrophages*;
NADPH Oxidase;
Phosphorylation;
Reactive Oxygen Species
- From:Biomolecules & Therapeutics
2018;26(2):191-200
- CountryRepublic of Korea
- Language:English
-
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 ROS, 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.
