Parthenolide, an inhibitor of the nuclear factor-κB pathway, ameliorates dextran sulfate sodium-induced colitis in mice

Background: Activation of nuclear factor-kappa B (NF-kappa B), which controls transcription of various proinflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). Parthenolide, a sesquiterpene lactone compound isolated from extracts of the herb Feverfew (Tanacetum parthenium), has been demonstrated to be a potent inhibitor of NF-kappa B activation. This study was designed to investigate the effects of parthenolide on an experimental murine colitis model. Materials and methods: Experimental colitis was induced by dextran sulfate sodium (DSS), and mice were divided into 3 groups: normal control, DSS + saline, and DSS + parthenolide. The disease activity index (DAI) and histological score were observed. The tumor necrosis factor (INF)-alpha and interleukin (IL)-1 beta levels were measured by enzyme-linked immunosorbent assay. Phospho-I kappa B alpha, I kappa B alpha and phospho-NF-kappa B p65 expression were assessed by western blot analysis. Myeloperoxidase (MPO) activity was determined by using MPO assay kit Results: Administration of parthenolide significantly reduced the severity of DSS-induced colitis as assessed by DAI and histological score, and resulted in downregulation of MPO activity and phospho-NF-kappa B p65 expression by the blockade of phosphorylation and subsequent degradation of I kappa B protein, strikingly reduced the production of TNF-alpha and 1L-1 beta. Conclusion: Parthenolide exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC. (C) 2011 Elsevier B.V. All rights reserved.