樗葉花椒醇抑制TPA所誘導的發炎
及促癌作用之研究

我國傳統民間常用草藥中往往具有抗氧化且安全無毒的特性，例如:類黃酮、胡蘿蔔素及天然多酚類。許多天然中草藥植物具有降低發炎與抑制腫瘤生長的成效。具有生物藥理活性天然有機全合成產物Ailanthoidol(AT)在1983年首度由Ishii等人，由皮部分分離(1)得到。屬於neolignan family之一（2），過去的研究已知像Lignans、neolignans及nor-neolignans類的結構式具有多樣化的生物活性，例如抗癌、抗增生、抗氧化、抗發炎、及癌症預防等作用。在本實驗中發現AT具捕捉自由基的能力。研究證實具有抗氧化或抗發炎的藥物往往也具有抑制TPA (12-O-tetradecanoylphorbol-13-acetate)的促癌作用(3-6)，實驗欲進一步評估AT對於抗發炎及抑癌促進作用的情形。首先在TPA誘發老鼠耳朵水腫作用下加入不同濃度AT (0.5 mM、1.0 mM及2.5 mM)分別能抑制有45﹪、68﹪、96﹪的效果，另外以老鼠背部皮膚癌指標酵素ornithine decarboxylase（ODC）之活性結果顯示81.5﹪、85.2﹪、91.3﹪的抑制作用，在COX-2與iNOS發炎反應性蛋白質表現上也有相類似的效果。相同的在H2O2及MPO分別也顯示有83﹪、90﹪、96﹪及58﹪、61﹪、97﹪的抑制效果，此外AT對於TPA誘導皮膚形態改變抑制試驗中作病理切片觀察，預先處理AT可有效地降低因TPA所造成的老鼠上皮細胞增生。另外前處理不同濃度的AT在老鼠皮膚腫瘤二階段癌化模式實驗加入癌細胞生長起始劑0.2 mol Benzo[a]pyrene (B[a]P)及癌細胞生長促進劑，TPA(0.5 nmol)證實，AT具有預防細胞癌化的作用，進一步可能具有抑制腫瘤細胞生長之功能，證實AT的確具有抑制TPA所誘導之發炎及癌促進的作用。

關鍵字

食茱萸；癌症的促進

並列摘要

Ailanthoidol (AT), a membr of neolignan, has been obtained from the stem woods of Zanthoxylum ailanthoides (1,2). Evidence demonstrated that neolignan and lignan exhibit a broad range of biological activites such as antiproliferation, antivirus, antioxidant, caner preventative and anti-inflammanatory. In the preliminary study, AT showed an effective antioxidant property. Further investigations showed that the topical application of AT (0.5, 1.0 and 2.5 mM) inhibited TPA-induced the incidence of edema in mouse ear to 45, 68 and 96%, respectively. The topical application of AT inhibited TPA (5 nmol)-caused induction of epidermal ornithine decarboxylase (ODC) and myeloperoxidase (MPO) activity. The same doses of AT also reduced the formation of hydrogen peroxide in the mouse skin to an inhibition of 83, 90 and 96%, respectively. In addition, biological analysis revealed the same AT inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein expression. Pre-application of AT also afforded significant as protection histopathological changes in TPA-induced hyperplasia on mouse skin. To investigate Topical application of AT with TPA three times one week for 24 weeks to mice previously Benzo[a]pyrene（B[a]P）inhibited the number tumors per mouse. Finally, our results indicate that AT can inhibit TPA-induced inflammation and tumor promotion.

並列關鍵字

Ailanthoidol ； Zanthoxylum ailanthoides ； TPA

參考文獻

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樗葉花椒醇抑制TPA所誘導的發炎及促癌作用之研究

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