Chebulagic acid (CA), a natural anti-oxidant, showed potent anti-inflammatory effects in LPS-stimulated RAW 264.7, a mouse macrophage cell line. These effects were exerted via inhibition of NO and PGE(2) production and down-regulation of iNOS, COX-2, 5-LOX, TNF-alpha and IL-6. CA inhibited NF-kappa B activation by LPS, and this was associated with the abrogation of 1KB-alpha phosphorylation and subsequent decreases in nuclear p50 and p65 protein levels. Further, the phosphorylation of p38, ERK 1/2 and JNK in LPS-stimulated RAW 264.7 cells was suppressed by CA in a concentration-dependent manner. LPS-induced generation of reactive oxygen species (ROS) was also effectively inhibited by CA. These results suggest that CA exerts anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages by inhibition of NF-kappa B activation and MAP kinase phosphorylation. (C) 2009 Elsevier Inc. All rights reserved.