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

Abstract：

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. 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 (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. CONCLUSION:Parthenolide exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zhao ZJ,Xiang JY,Liu L,Huang XL,Gan HT

doi

10.1016/j.intimp.2011.11.007

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

169-74

issue

1

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(11)00447-4

journal_volume

12

pub_type

杂志文章

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