Sphondin及Byakangelicol抑制人類肺臟上皮細胞環氧酵素-2表現之作用機轉探討

Action Mechanisms of Sphondin and Byakangelicol on the Suppression of Cyclooxygenase-2 Expression in human Pulmonary Epithelial Cell

張嘉紋(CHANG CHIA WEN)

指導教授 ： 林建煌 博士 ； 楊玲玲 博士

臺北醫學大學/藥學院/生藥學研究所/碩士(2000年)

摘要

本論文主要在探討furanocoumarin類之植物成分於人類肺臟上皮細胞 (A549) 受IL-1 beta引發之COX-2表現及PGE2釋放的影響。結果發現 angelicin type furanocoumarin的四個成份angelicin, pimpinellin, isobergapten及sphondin；psoralen type furanocoumarin中之七個成分bergapten, byakangelicin, byakangelical, isopimpinellin, oxypeucedanin, oxypeucedanin hydrate和xanthotoxin均可抑制IL-1 beta引發之COX-2表現及PGE2釋放，而psoralen及phellopterin沒有明顯的抑制作用。綜合以上結果，將具有明顯活性之sphondin及byakangelicol來探討其抑制IL-1 beta引發COX-2表現之作用機轉。 Sphondin及byakangelicol以濃度相關的方式抑制IL-1beta引發COX-2表現及PGE2的釋放，進一步實驗證實byakangelicol與選擇性COX-2抑制劑NS398以濃度相關的方式抑制COX-2的活性，但是sphondin則對COX-2的活性不具影響。另外，sphondin及byakangelicol有抑制IL-1beta引發p65 NF-kappa B轉位及I kappa B-alfa?分解的作用，由electrophoretic mobility shift assay (EMSA) 的結果也發現sphondin及byakangelicol有抑制NF-kappa B的活化。然而sphondin及byakangelicol並不影響IL-1 bata 引發p44/42 MAPK的活化。綜合以上結果可推論sphondin及byakangelicol可能是經由抑制IL-1 bata引發NF-kappa B的活化而抑制COX-2蛋白的表現，進而抑制PGE2的釋放，而byakangelicol同時也具有抑制COX-2的活性。

關鍵字

環氧酵素 ； 前列腺素

並列摘要

The inhibitory effect of furanocoumarin compounds on the interleukin-1? (IL-1?)-induced cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) release was studied in human pulmonary epithelial cell line (A549). We found that angelicin type furanocoumarin compounds, angelicin, isobergapten, pimpinellin and sphondin all inhibited IL-1?-induced COX-2 expression and PGE2 release. Psoralen type furanocoumarin compounds bergapten, byakangelicin, byakangelicol, isopimpinellin, oxypeucedanin, oxypeucedanin hydrate and xanthotoxin also inhibited IL-1?-induced COX-2 expression and PGE2 release, while bergapten and phellopterin had no effect. Furthermore, we choose sphondin and byakangelicol among furanocoumarin compounds to investigate their action mechanisms on the suppression of IL-1?-induced COX-2 expression and PGE2 release. Sphondin and byakangelicol inhibited dose-dependently the IL-1beta-induced COX-2 expression and PGE2 release. Byakangelicol and NS398, a selective COX-2 inhibitor, inhibitor dose-dependently COX-2 activity, while sphondin had no effect. Sphondin and byakangelicol inhibited IL-1beta-induced p65 nuclear factor-kappa B (NF-kappa B) translocation and I kappa B-alfa? degradation. Furthermore, the IL-1 bata-induced activation of NF-kappa B-specific DNA-protein complex formation was also inhibited by sphondin and byakangelicol. However, Sphondin and byakangelicol had no effect of IL-1 bata-induced p44/42 MAPK activation. The results suggest that the inhibitory mechanism of sphondin and byakangelicol on the IL-1 bata-induced COX-2 expression and PGE2 release may through the suppression of NF-kappa B activation. On the other hand, the inhibitory effect of byakangelicol on IL-1 bata-induced PGE2 release may partly through the suppression of COX-2 enzyme activity.

並列關鍵字

cyclooxygenase ； prostaglandin E2

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