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

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-kappa B (NF kappa B) subunit and the dependent transcriptional activity of NF kappa B by blocking phosphorylation of inhibitor kappa B (I kappa B)alpha and p65 and subsequent degradation of I kappa B alpha. Transient transfection experiments using NF kappa B reporter constructs indicated that MSE inhibits the transcriptional activity of NF kappa B 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 NF kappa B 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. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.