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茶萃取物對於促發炎信號的影響

The Effects of Tea Extracts on Proinflammatory Signaling

摘要


背景 對實體皮膚腫瘤所作之放射線療法(radiotherapy, R/T),最常見之副作用為皮膚毒性。它在處理時會造成治療的差距,亦因此會造成癌症治療之障礙。目前,在許多國家中對於輻射線治療期間所引發之皮膚病並無標準療法。在本研究中,我們使用局部塗抹茶萃取物來探究輻射線誘發之皮膚毒性期間的效果。我們提出綠茶最其有潤濕性的EGCG茶萃取物來比較其效果並且探討其分子作用機轉。 方法 數據來自60位頭頸部位或骨盆部位癌症之病人,其局部接受綠茶或紅茶萃取物治療之回歸分析。茶萃取物之調節比較效果為由人類單核球釋出之IL-lβ、IL-6、IL-8、TNF-α與PGE2(prostaglandin E2)的能力。評估茶萃取物對26S蛋白小體功能(proteasome function)之效果。NFkB活性則以EMSAs檢測。巨噬細胞暴露茶萃取物之後的生命力和輻射反應則利用MTT測定法。 結果 茶萃取物可以使皮膚完整性恢復。茶萃取物會抑制蛋白小體功能以及抑制細胞激素釋出。在複雜的依賴caspase方式下(caspase-dependent manner),茶萃取物會使NFkB活性發生改變,此乃來自EGCG之作用不同。除此之外,包括茶萃取物以及EGCG,稍具有使巨噬細胞不受離子輻射侵害之保護作用。 結論 對於病人遭受急性短期輻射所誘發的皮膚毒性,茶萃取物為相當有效且廣泛可採用之治療選擇。分子作用機轉成為有益效果是複雜的,並且最可能並非唯一的只依賴如EGCG的茶多酚而已。

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並列摘要


Background: Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin during radiotherapy exists. In this study, we explored the effect of topically-applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most-active moiety of green tea. Methods: Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed retrospectively. Tea extracts were compared for their ability to modulate IL-1β, IL-6, IL-8, TNF α and PGE2 release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-κB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays. Results: Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-κB activity was altered by tea extracts in a complex, caspase-dependent manner which differed from the effects of epigallocatechingallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation. Conclusion: Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate.

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