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, CHBrO) 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-α, interleukin-1β, 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.

Asperuloside and Asperulosidic Acid Exert an Anti-Inflammatory Effect via Suppression of the NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

“…Actually, two distinct cyclooxygenase isoforms, namely COX-1 and COX-2, are commonly used as molecular targets for non-steroidal anti-inflammatory drugs (NSAIDs) [ 30 ]. COX-1 is expressed ubiquitously and constitutively, which plays a housekeeping role in processes, such as gastrointestinal mucosa protection, while COX-2 is not constitutively expressed in the cell, but can be activated by inducers, such as endotoxins, cytokines, and growth factors [ 31 ]. In LPS-induced macrophages, COX-2 can convert arachidonic acid to PGG 2 and, finally, to PGE 2 [ 32 , 33 , 34 ].…”

Progress of Bromophenols in Marine Algae from 2011 to 2020: Structure, Bioactivities, and Applications

“…In 1967, the first two BPs were isolated from the red algae Rhodomela larix [ 3 ]. Over the past few decades, a great number of BPs were isolated from various marine algae species including red algae [ 4 , 5 , 6 , 7 , 8 , 9 ], green algae [ 10 , 11 , 12 , 13 , 14 ], and brown algae [ 15 , 16 , 17 , 18 , 19 ]. Some BPs are also found in other marine organisms such as sponges [ 18 , 20 , 21 , 22 , 23 , 24 ], ascidians [ 25 , 26 , 27 ], mussels [ 28 ], polychaetes [ 29 ], and marine proteobacteria [ 30 ].…”

Anti-Inflammatory and Antioxidant Effects of Carpesium cernuum L. Methanolic Extract in LPS-Stimulated RAW 264.7 Macrophages

“…The importance of ERK on inflammation, in particular, has been well reported. ERK is majorly correlated with LPS-induced macrophages inflammation [ 27 , 45 – 48 ]. Additionally, it was reported that the suppression of ERK successfully inhibited inflammation in mouse and rabbit models [ 49 , 50 ].…”