AURENTIACIN INHIBITS INFLAMMATORY MEDIATORS BY SUPPRESSING NF-κB AND MAPKS ACTIVATION IN LIPOPOLYSACCHARIDE-INDUCED RAW 264.7 MACROPHAGE

Abstract

Syzygium samarangense is locally known in the Philippines as “makopa”. The plant has been reported to have antibacterial, antidiabetic and immunostimulant activities. A number of compounds have been isolated from this plant. Among these, we investigated anti-inflammatory activity of the flavonoid 2’-hydroxy-4’,6’-dimethoxy-3’-methylchalcone (aurentiacin) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. Exposure of RAW264.7 cells to aurentiacin dramatically inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner in LPS -stimulated RAW264.7 cells, respectively. In addition, LPS-induced Mitogen-Activated Protein Kinases (MAPKs ; ERK, JNK and p38) activations were inhibited by aurentiacin treatment in a time-dependent manner. Aurentiacin also reduced nuclear translocation of NF-κB p65 subunit. Interestingly, aurentiacin blocked NF-κB p65 activation, which occurred through phosphorylating at Ser 536. These results suggest that aurentiacin inhibits the production of NO and PGE2 through the down-regulation of iNOS and COX-2 gene expression via reducing of NF-κB and MAPKs activation. Therefore, aurentiacin might provide a potential therapeutic approach for inflammation- associated diseases.