The aim of the present study was to investigate the effects of piperine on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved. RAW264.7 cells were pretreated with piperine at 10, 50 or 100 mu g/ml and subsequently stimulated with LPS (1 mu g/ml) for 24 h. We found that piperine inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO) induced by LPS. Piperine significantly decreased LPS-stimulated gene expression and production of tumor necrosis factor-alpha (TNF alpha), inducible NO synthase (iNOS) and COX-2 in RAW264.7 cells. Piperine inhibited the LPS-mediated activation of nuclear factor-kappa B (NF-kappaB) by suppressing the degradation of inhibitor-kappa B proteins (I kappa B) and the translocations of p65 subunit of NF-kappa B from the cytosol to the nucleus. Our results demonstrate the anti-inflammatory activity of piperine in RAW264.7 cells; suggesting that piperine may be a potential agent in the treatment of inflammation. (C) 2013 Elsevier Inc. All rights reserved.