Bis (3-bromo-4,5-dihydroxybenzyl) ether, a novel bromophenol from the marine red alga Polysiphonia morrowii that suppresses LPS-induced inflammatory response by inhibiting ROS-mediated ERK signaling pathway in RAW 264.7 macrophages

Abstract

Inflammation is a pathophysiological defense response against various factors for maintaining homeostasis in the body. However, when continued excessive inflammation becomes chronic, various chronic diseases can develop. Therefore, effective treatment before chronic inflammation development is essential. Bis (3-bromo-4,5-dihydroxybenzyl) ether (BBDE, C14H12Br2O5) is a novel bromophenol isolated from the red alga Polysiphonia morrowii. The beneficial physiological functions of various bromophenols are known, but whether BBDE has beneficial physiological functions is unknown. Therefore, we first investigated whether BBDE exerts any anti-inflammatory effect. We demonstrated that BBDE inhibits inflammation by reducing inflammatory mediators, such as nitric oxide, prostaglandin E2, iNOS, COX2, and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6), in LPS-induced macrophage cells. To examine the mechanism of action by which BBDE inhibits inflammation, we confirmed its effect on signal transduction and ROS generation. BBDE selectively inhibited ERK phosphorylation in the mitogen-activated protein kinase pathways. Moreover BBDE suppressed LPS-induced ROS generation in RAW 264.7 macrophage cells. Inhibition of LPS-induced ROS generation by BBDE also caused ERK inactivation and an inflammatory reaction. Therefore, BBDE inhibits LPS-induced inflammation by inhibiting the ROS-mediated ERK signaling pathway in RAW 264.7 macrophage cells and thus can be useful for treating inflammatory diseases.