Oleifolioside A, a New Active Compound, Attenuates LPS-Stimulated iNOS and COX-2 Expression through the Downregulation of NF-?B and MAPK Activities in RAW 264.7 Macrophages.

ABSTRACT: Oleifolioside A, a new triterpenoid compound isolated from Dendropanax morbifera Leveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Consistent with these findings, oleifolioside A was further shown to suppress the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) in a dose-dependent manner at both the protein and mRNA levels and to significantly inhibit the DNA-binding activity and transcriptional activity of NF-?B in response to LPS. These results were found to be associated with the inhibition of the degradation and phosphorylation of I?B-? and subsequent translocation of the NF-?B p65 subunit to the nucleus. Inhibition of NF-?B activation by oleifolioside A was also shown to be mediated through the prevention of p38 MAPK and ERK1/2 phosphorylation. Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-?B and MAPK signaling pathways.

SUBMITTER: Yu HY 

PROVIDER: S-EPMC3405816 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature