Parthenolide, an inhibitor of the nuclear factor-κB pathway, ameliorates dextran sulfate sodium-induced colitis in mice.
Mots clés
Abstrait
BACKGROUND
Activation of nuclear factor-kappa B (NF-κB), which controls transcription of various pro-inflammatory 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-κB activation. This study was designed to investigate the effects of parthenolide on an experimental murine colitis model.
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 (TNF)-α and interleukin (IL)-1β levels were measured by enzyme-linked immunosorbent assay. Phospho-IκBα, IκBα and phospho-NF-κB 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-κB p65 expression by the blockade of phosphorylation and subsequent degradation of IκB protein, strikingly reduced the production of TNF-α and IL-1β.
CONCLUSIONS
Parthenolide exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.
