Anti-inflammatory effect of Momordica grosvenori Swingle extract through suppressed LPS-induced upregulation of iNOS and COX-2 in murine macrophages

Abstract

Momordica grosvenori Swingle, a traditional medicinal herb, is known to possess anti-inflammatory anti-oxidative, anti-diabetic, and nephroprotective activities. Here, we investigated the inhibitory effects of M. grosvenori Swingle extract (MSE) on the induction of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses demonstrated that MSE significantly blocked protein and mRNA expression of iNOS and COX-2 in LPS-induced macrophages. Treatment with MSE resulted in the reduction of LPS-induced nuclear translocation of nuclear factor-κB (NFκB) subunit and the dependent transcriptional activity of NFκB by blocking phosphorylation of inhibitor κB (IκB)α and p65 and subsequent degradation of IκBα. Transient transfection experiments using NFκB reporter constructs indicated that MSE inhibits the transcriptional activity of NFκB in LPS-stimulated mouse macrophages. MSE also inhibited LPS-induced activation of PI3K/Akt, extracellular signal-regulated kinase 1/2 and p38 MAPK. Taken together, these results show that MSE down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFκB by interfering with the activation PI3K/Akt/IKK and MAPK. These results have important implication for using MSE towards the development of effective anti-inflammatory agents.