Anti-inflammatory effect of phlorofucofuroeckol A on lipopolysaccharide-induced RAW 264.7 macrophages

Abstract

Phlorofucofuroeckol A (PFF-A) is a phloroglucinol derivative isolated from the edible brown algae Ecklonia stolonifera and has been shown to possess various biological activities. In this study, the effect of PFF-A on the regulation of iNOS and COX-2 which are key inflammatory proteins responsible for excessive production of NO and PGE₂, respectively, was investigated using the LPS-treated RAW 264.7 cells. Treatment with 20 M of PFF-A led to strong inhibition of iNOS and COX-2 protein and mRNA expressions in the LPS-treated RAW 264.7 cells. Data of luciferase assays demonstrated that PFF-A treatment largely suppressed the iNOS or COX-2 promoter-driven luciferase expression in the LPS-treated RAW 264.7 cells. PFF-A also had an inhibitory effect on the NF-κB-promoter driven expression. Moreover, PFF-A had an ability to inhibit activation of Akt, p38 MAPK, ERK-1/2 and JNK-1/2, and to reduce cellular ROS in the LPS-treated RAW 264.7 cells. Taken together PFF-A inhibits iNOS and COX-2 expression in the LPS-treated RAW 264.7 cells through the NF-κB-dependent transcriptional down-regulation in association with inhibition of ERK-1/2, JNK-1/2, p38 MAPK, and Akt, and with reduction of cellular ROS. These results suggest an important implication for using PFF-A toward the development of an effective anti-inflammatory agent.