Anti-inflammatory activity of 4-methoxycinnamyl p-coumarate isolated from Etlingera pavieana rhizomes in lipopolysaccharide-induced macrophages

Abstract

Nitric oxide (NO) and prostaglandins E2 (PGE₂) play a critical role as inflammatory mediators but overproduction can lead to inflammatory diseases. Regulation of NO and PGE₂ secretion is a particular target in the development of anti-inflammatory agents. 4-methoxycinnamyl p-coumarate (MCC) was isolated from rhizomes of Etlingera pavieana by NO inhibitory activity-guided isolation. In this study, we evaluated the inhibitory effect of MCC on NO and PGE₂ production as well as enzymatic activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MTT assay showed that MCC at 6.25 to 25 ??M has no significant cytotoxicity compared to unstimulated control cells. MCC significantly reduced NO and PGE₂ production with IC₅₀ values of 8.5??0.4 and 26.2??3.7 ??M, respectively. MCC at concentrations to 25 ??M significantly inhibited iNOS enzyme activity but it did not suppress COX-2 enzyme activity. Interestingly, MCC itself did not reduce COX-1 expression and reversed the suppressive effect on COX-1 expression in LPS-stimulated RAW 264.7 macrophages. Collectively, these results suggest that MCC inhibits NO and PGE₂ production, as well as iNOS enzyme activity. MCC exhibits potent anti-inflammatory action with selective inhibitory effect on COX expression and might be used in the development of an anti-inflammatory agent with fewer side effects than current drugs.