YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

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.

Antioxidant and Anti-Inflammatory Effects of White Mulberry (Morus alba L.) Fruits on Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

“…Overproduction of ROS and reduced antioxidant capacity can result in a redox imbalance, inducing the inflammatory response and oxidative stress eventually leading to the formation of various pathophysiological lesions [ 24 ]. Consistent with the results of previous studies [ 25 , 26 , 27 ], in this study, LPS increased ROS generation in stimulated RAW 264.7 macrophages ( Figure 2 ). Co-treatment of LPS-stimulated RAW 264.7 macrophages with white mulberry fruit extract and fractions resulted in significant reductions in ROS levels.…”

Development and Optimization of Nanoemulsion from Ethanolic Extract of Centella asiatica (NanoSECA) Using D-Optimal Mixture Design to Improve Blood-Brain Barrier Permeability

“…Then, the cells were gently washed three times with HBSS to remove excess dye solution. Finally, the fluorescence intensity was measured at an excitation wavelength of 485 nm and an emission wavelength of 520 nm after 200 µ L of HBSS was loaded into the wells [ 32 ].…”

Licorice zinc suppresses melanogenesis via inhibiting the activation of P38MAPK and JNK signaling pathway in Balb/c mice skin

“…There is a growing body of evidence indicating that the P38MAPK and JNK signaling pathway contributes to melanogenesis via colaborating to inflammatory and oxidants 26 , 27 . Reactive oxygen species (ROS) production and inflammatory mediators were suppressed when P38MAPK and JNK signaling pathway was suppressed, what is more, the current study indicated that inhibition of inflammatory response and oxidative stress could reduce melanogenesis 19 .…”