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研究生:孫瑞強
研究生(外文):Jui-Chiang Sun
論文名稱:六種多酚化合物抑制腫瘤壞死因子-α和核因子-κB途徑的對接預測
論文名稱(外文):Docking Prediction for Six Phenoic Compounds Inhibiting TNF-α and NF-κB Pathway
指導教授:李世傑,李桂仁.
指導教授(外文):LEE, Shih-Chieh and Kuei-Jen Lee.
口試委員:蔡明勳,李泰林,張培均,胡文品.
口試委員(外文):Ming-Shiun Tsai ,Tai-Lin Lee ,Pei-Chun Chang ,Wen-Pin Hu .
口試日期:2013-05-31
學位類別:博士
校院名稱:大葉大學
系所名稱:生物產業科技學系
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:110
中文關鍵詞:薑黃素兒茶素芥子醇丁香甙雷公藤甲素木犀草素NF-κB途徑
外文關鍵詞:CurcuminEGCGsyringinsinapyl alcoholTriptolideLuteolinNF-κB pathway
相關次數:
  • 被引用被引用:0
  • 點閱點閱:198
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  • 下載下載:6
  • 收藏至我的研究室書目清單書目收藏:0
本研究從具有消炎作用的中藥中,選取藥效較強而且常被使用的六種中藥多酚:薑黃素、兒茶素、芥子醇、丁香甙、雷公藤甲素和木犀草素,分為兩部分的主題來進行研究;第一部分是以薑黃素、兒茶素、芥子醇、丁香甙、雷公藤甲素和木犀草素等六種多酚以Autodock 4的軟體來作和TNF-α的對接預測;發現在當作以抑制TNF-α的消炎藥劑的單方方面,用雷公藤甲素或是薑黃素會比較好,這二者的藥效既強又穩定。若用做消炎的複方時,因為TNF–α的口袋是三個,根據研究結果,發現有三種使用方法:(a)同時使用薑黃素,兒茶素,芥子醇和木犀草素。(b)同時使用薑黃素,丁香甙,芥子醇和木犀草素。(c)同時使用兒茶素,丁香甙,和雷公藤甲素和木犀草素。
第二部分是以木犀草素當作小分子,胞內的NF-κB途徑 ﹙TNFR1、 TRAF2、TRADD 、RIP1、IKKβ﹚分別當作大分子,以Autodock 4的軟體來作對接預測;發現木犀草素可以強烈的抑制TRAF2、TNFR1 和 TRADD三者的功能,木犀草素可以聯結住RIP1,阻斷RIP1訊號的傳遞;木犀草素也和IKKβ的C-末端強力結合,阻止IKKβ和IKKα以及IKKγ形成三聚體,產生功能。也就是木犀草素可作為細胞外的TNF-α的抑制劑,也可以是細胞內NF-κB途徑的抑制劑。
本研究發現這六種多酚除了可以在細胞外以抑制TNF-α,產生消炎作用以外,其中的木犀草素還可以在細胞內以抑制NF-κB途徑,來產生消炎作用。
In this article, we select 6 frequently used polyphenols with strong efficacy from anti-inflammatory herbal medicines: curcumin、 EGCG (epigallocatechin -3- gal -late) 、sinapyl alcohol、syringin, triptolide and luteolin to perform docking study.
First part addresses on extracellular links to TNF-α. We dock TNF–α with curcumin、 EGCG、 sinapyl alcohol、 syringing、triptolide and luteolin by Autodock 4, respectly. We discover that triptolide and curcumin have stronger effect and better stability on inhibiting TNF-α in these six polyphenols. There are three combinectives of compounds on inhibiting TNF-α: (1). Curcumin、 EGCG 、 sinapyl alcohol and luteolin. (2). Curcumin、 sinapyl alcohol 、 syringin and luteolin. (3). EGCG、 syringing、triptolide and luteolin.
In the second part, we discuss luteolin inhibits NF-κB pathway in intracellular.We use luteolin as ligand, NF-κB pathway in intracellular as macromolecular to perform docking prediction with Autodock 4. We discoverd that luteolin can strongly inhibit TRAF2 and TNFR1; dock with RIP1 to block the signal passing of RIP1; strongly dock with C-terminal of IKKβ to inhibit IKKβ、 IKKα and IKKγ from forming trimer. In other words, luteolin can be an inhibitor for TNF-α on extracellular and NF-κB pathway in intracellular.
目錄

封面內頁
簽名頁
中文摘要……………………………………………………........iii
英文摘要……………………………………………………........v
誌謝……………………………………………………...........vi
目錄……………………………………………………...........vii
圖目錄…………………………………………………….........ix
表目錄…………………………………………………….........xi

第一章 緒言…………………………………………………...1
第一節 研究背景與動機……………………………. 1
第二節 研究問題與目的……………………………. 2
第二章 文獻回顧……………………………………………...6
第一節 TNF-α和NF-κB對於人體的保護及引起
的疾病……………………………………….... 6
第二節 六種多酚:薑黃素、兒茶素、芥子醇、丁香
甙、雷公藤甲素和木犀草素抑制TNF-α的活性的相關研究……………………………13
第三節 木犀草素抑制核因子-κB 的相關研究……17
第四節 SWISS-MODEL Workspace 的相關研究…18
第五節 Autodock 4 (包含ADT)的相關研究………20
第六節 LIGPLOT 的相關研究……………………. 21
第七節 SwissPdb Viewer 的相關研究……………22
第八節 PROCHECK 的相關研究………………… 22
第九節 VERIFY3D 的相關研究 ………………… 23
第十節 ERRAT 的相關研究……………………… 24
第十一節 ChemSpider………………………………. 24
第三章 材料與方法…………………………………………..25
第一節 六種多酚對於腫瘤壞死因子-α的對接預測………25
第二節 木犀草素抑制核因子-κB途徑的對接預測…………34
第四章 結果與討論…………………………………………...………………44
第一節 六種多酚對於腫瘤壞死因子-α的對接預測的結果…44
第二節 木犀草素抑制核因子-κB的對接預測的結果……………60
第五章 結論…………………………………………………... 72
參考文獻……………………………………………..………... 76
附錄…………………………………………………………….……………89圖目錄
圖目錄

圖3.1 儲存到AutoDock中的1A8MB的DeepView project 的pdb檔………………………28
圖3.2 6個多酚的化學結構:(a).薑黃素 (b).兒茶素(c).芥子醇 (d).丁香甙 (e).雷公藤甲素﹙f﹚.木犀草………….………………33
圖3.3a 儲存到AutoDock中的 TNFR(41到201) 1extA的 Deep View project的pdb檔………………………… 38
圖3.3b 儲存到AutoDock中的TNFR(356到442)1ichA的DeepView project的pdb檔……………………..…… 39
圖3.4 儲存到AutoDock中的 TRADD(1f2hA)的Deep View project 的pdb檔……………………………………… 40
圖3.5 儲存到AutoDock中的 TRAF2(1ca9B)的DeepView project的pdb檔..……………………………………… 41
圖3.6 儲存到AutoDock中的 RIP1﹙1qcfA﹚的DeepView projec的pdb檔……………………………………… 42
圖3.7 儲存到AutoDock中的IKKβ﹙1cm8B﹚的DeepView project的pdb檔……………………………………… 43
圖4.1 這六個多酚和TNF-α表面的對接結果……………… 52
圖4.2 TNF-α中相同口袋的對接配體群…………………… 53
圖4.3 配體:薑黃素、兒茶素、芥子醇、丁香甙、雷公藤甲素和木犀草素的凡得瓦爾力和氫鍵作用力………54
圖4.4 對接結果中的π–π型態原子之間的作用力和π–陽離子的用力……………………………………………57
圖4.5 對接結果中的π–π型態原子之間的作用力和π–陽離子的作用力………………………………………68

表目錄
表3.1 TNF–α﹙1A8MB﹚同源模型的模板和品質……….. 27
表3.2 在ChemSpider( http://www.chemspider.com/)的小分 子的最新發表的資料…………31
表3.3 模板和同源模型的品質……………………………. 37
表4.1 以AUTODOCK 4.0所計算出的能量能量(以kcal/ mol表示)…………………………………………48
表4.2 氫鍵作用力以及每一個氫鍵的能量…………………58
表4.3 凡得瓦爾力…………………………………………… 59
表4.4 AUTODOCK 4.0計算出的能量(kcal/mol)………….67
表4.5 氫鍵相互作用和每一個鍵的能量……………………69
表4.6 凡得瓦力作用力………………………………………70
表4.7 疏水性作用力………………………………………… 71

附錄

附錄1 名詞對照表…………………………………………… 89
附錄2 發表論文列表………………………………………… 94
附錄3發表論文………………………………………………. 95
附錄4 SCI發表論文…………………………………………. 96
附錄5 autodock(介紹)…………………………………………97
附錄6 ChemSpider(介紹)…………………………………….100



















表目錄

表3.1 TNF–α﹙1A8MB﹚同源模型的模板和品質……….. 27
表3.2 在ChemSpider( http://www.chemspider.com/)的小分 子的最新發表的資料…………..................................
31
表3.3 模板和同源模型的品質……………………………. 37
表4.1 以AUTODOCK 4.0所計算出的能量能量(以kcal/ mol表示)……………………………………………
48
表4.2 氫鍵作用力以及每一個氫鍵的能量………………… 58
表4.3 凡得瓦爾力…………………………………………… 59
表4.4 AUTODOCK 4.0計算出的能量(kcal/mol)…………. 67
表4.5 氫鍵相互作用和每一個鍵的能量…………………… 69
表4.6 凡得瓦力作用力……………………………………… 70
表4.7 疏水性作用力………………………………………… 71










附錄

附錄1 名詞對照表…………………………………………… 89
附錄2 發表論文列表………………………………………… 94
附錄3發表論文………………………………………………. 95
附錄4 SCI發表論文…………………………………………. 96
附錄5 autodock(介紹)………………………………………… 97
附錄6 ChemSpider(介紹)…………………………………….. 100


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