(3.237.97.64) 您好!臺灣時間:2021/03/09 10:02
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:劉祐瑄
研究生(外文):Yu-Hsuan Liu
論文名稱:樟芝三萜類成分抗血癌之相關藥理計算分析研究
論文名稱(外文):Study of computational analysis of Antrodia camphorate triterpenoid’s anti-leukemia pharmacology
指導教授:鄭志鴻鄭志鴻引用關係
指導教授(外文):Tzu-Hurng Cheng
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:生物科技學系碩士班
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:2014
畢業學年度:102
語文別:中文
論文頁數:62
中文關鍵詞:樟芝三萜血癌抗血癌急性早幼粒細胞白血病
外文關鍵詞:Antrodia camphoratetriterpenoidsleukemiaanti-leukemiaAcute promyelocytic leukemia
相關次數:
  • 被引用被引用:2
  • 點閱點閱:170
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
樟芝是中國傳統民間用藥之一,常用於抗發炎、治療皮膚搔癢、解酒精中毒等,有研究指出,它有許多成分: 多糖、三萜、腺苷等(1),其中,三萜類具有抗血癌、抗乳腺癌、抗肺癌等(2)功效。
急性早幼粒細胞白血病(acute promyelocytic leukemia,APL)是因15(q22)和17(q11–12)染色體互相移位造成,使PML, RARα基因融合,讓早幼粒細胞異常增殖和積聚在骨髓及血液中,且致死率高(3)。有研究指出樟芝的Zhankuic acid A三萜,與TRAIL(TNF-related apoptosis-inducing ligand)結合,使DR5(Death receptor 5)表現,造成NFκB活化、Bax/Bcl-2表現上升,使HL-60細胞凋亡(4)。
本研究比較不同藥物三萜,如:樟芝、人参、甘草、柴胡、茯苓,加上市售抗血癌藥物,利用Discovery Studio○R計算分析,分析不同藥物三萜及抗血癌藥物與腫瘤壞死因子(TNF)受體相關死亡結構域蛋白(TRADD)的對接情形與對接分數,探討樟芝三萜是否為最主要抗血癌成分。
初步結果顯示:樟芝三萜結構及抗血癌藥物,都與蛋白接合。樟芝三萜結構較基本,分子較小,上面含一些OH基及氫原子,較易有氫鍵鍵節與蛋白接合,所以,接合較穩固,對接分數也較高。

Antrodia camphorate(AC) is one of the traditional Chinese folk medicine, often used in anti-inflammatory, to treat skin itching, solution alcoholism, etc.Some reports have suggested that it has many ingredients: polysaccharides, triterpenes, adenosine(1),triterpenoids with anti-leukemia, breast cancer, lung cancer (2) effect.
Acute promyelocytic leukemia (APL) is the result of reciprocal translocation between chromosomes 15(q22) and 17(q11–12),making the PML, RARα gene fusion, so promyelocytic abnormal proliferation and accumulation in the bone marrow and blood, and the mortality rate is very high(3).AC in Zhankuic acid A triterpene composition,through TNF-related apoptosis-inducing ligand(TRAIL) induced the expression of death receptor 5(DR5), the DR5 expression,resulting in NFκB activation, Bax/Bcl-2 increase expression, induced HL-60 cells apoptosis(4).
This study compared numbers of different medicinal triterpenoids, such as: Antrodia, Ginseng, Licorice, Bupleurum, Poria and anti-leukemia medicine, using the Discovery Studio○Rcomputational analysis, different kinds of medicines triterpenoids and anti-leukemia medicine analysis and Tumor necrosis factor (TNF)-receptor 1-associated death domain protein (TRADD) docking situations and docking scores, and explored whether AC triterpenoids is the most important ingredient in its anti-leukemia effect.
Preliminary results showed that AC triterpenoid structure and anti-leukemia medinice are bonding with protein. AC triterpenoid structure is relatively basic, small molecules, and also some OH group and the hydrogen atoms, more to have hydrogen bonding and protein bonding, therefore, the more firmly bonded docking score is higher.

摘要 ........................................................................................................................ VII
Abstract ................................................................................................................ VIII
第一章 前言 ............................................................................................................. 1
第一節 研究背景 .............................................................................................. 1
一、血癌簡介 ............................................................................................. 1
二、樟芝簡介 ............................................................................................. 2
三、三萜介紹 ............................................................................................. 3
四、樟芝三萜介紹 ..................................................................................... 3
五、人參三萜介紹 ..................................................................................... 3
六、甘草三萜介紹 ..................................................................................... 4
七、柴胡三萜介紹 ..................................................................................... 4
八、茯苓三萜介紹 ..................................................................................... 4
九、抗血癌藥物分子介紹 ......................................................................... 5
十、腫瘤壞死因子(TNF)受體相關死亡結構域蛋白(TRADD)簡介 ..................................................................................................................... 5
第二節 研究目的 .............................................................................................. 5
第二章 研究方法 ..................................................................................................... 6
第三章 研究結果 ................................................................................................... 13
第一節 樟芝三萜與Tumor necrosis factor (TNF)-receptor 1-associated death domain protein(TRADD)對接情形 ................................................................. 13
第二節 人參三萜與Tumor necrosis factor (TNF)-receptor 1-associated death domain protein(TRADD)對接情形 ................................................................. 13
第三節 甘草三萜與Tumor necrosis factor (TNF)-receptor 1-associated death domain protein(TRADD)對接情形 ................................................................. 13
III
第四節 柴胡三萜與Tumor necrosis factor (TNF)-receptor 1-associated death domain protein(TRADD)對接情形 ................................................................. 14
第五節 茯苓三萜與Tumor necrosis factor (TNF)-receptor 1-associated death domain protein(TRADD)對接情形 ................................................................. 14
第六節 抗血癌藥物與Tumor necrosis factor (TNF)-receptor 1-associated death domain protein(TRADD)對接情形 ....................................................... 14
第四章 研究結果與討論 ....................................................................................... 15
參考文獻(References) ............................................................................................ 16

16
參考文獻(References)
1.Zong-Hua Ao,Zheng-Hong Xu,Zhen-Ming Lub,Hong-Yu Xu,Xiao-Mei Zhanga,Wen-Fang Dou."Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases,"Journal of Ethnopharmacology,2009,121,194-212.
2.Wan-Chi Tsai Shih-Shen Lin,Ming-Yung Chou,Yi-Ting Shen,Chih-Hao Wu, Chi-Chiang Yang,Yew-Min Tzeng."Methylantcinate A induces tumor specific growth inhibition in oral cancer cells via Bax-mediated mitochondrial apoptotic pathway,"Bioorganic & Medicinal Chemistry Letters,2010,20,6145-6148.
3.Dae-Young Kim,Je-Hwan Lee,Jung-Hee Lee,Sung-Doo Kim,Sung-Nam Lim, Yun-suk Choi,Young-Shin Lee,Young-Ah Kang,Miee Seol,Mi-jin Jeon, Joo-Youn Kim,Kyung-Hwa Lee,Yeon-Joo Lee,Kyoo-Hyung Lee. "Significance of fibrinogen, D-dimer, and LDH levels in predicting the risk of bleeding in patients with acute promyelocytic leukemia, "Leukemia Research,2011,35,152-158.
4.Mei-Chin Lu,Ying-Chi Du,Jiunn-Jye Chuu,Shiuh-Lin Hwang,Pao-Chuan Hsieh,Chih-Sheng Hung,Fang-Rong Chang,Yang-Chang Wu."Active extracts of wild fruiting bodies of Antrodia camphorate (EEAC) induce leukemia HL 60 cells apoptosis partially through histone hypoacetylation and synergistically promote anticancer effect of trichostatin A,"Arch of Toxicology,2009,83,121-129.
5.Ying-Chi Du,Fang-Rong Chang,Tung-Ying Wu,Yu-Ming Hsu,El-Shazly Mohamed,Chieh-Fu Chen,Ping-Jyun Sung,Yan-Yu Lin,Yi-Hsin Lin, Yang-Chang Wu,Mei-Chin Lu."Antileukemia component, dehydroeburicoic acid from Antrodia camphorate induces DNA damage and apoptosis in vitro and in vivo models,"Phytomedicine,2012,19,788-796.
17
6.Mei-Chin Lu,El-Shazly Mohamed,Tung-Ying Wu,Ying-Chi Du,Tun-Tschu Chang,Chieh-Fu Chen,Yu-Ming Hsu,Kuei-Hung Lai,Ching-Peng Chiu,Fang-Rong Chang,Yang-Chang Wu."Recent research and development of Antrodia cinnamomea,"Pharmacology & Therapeutics,2013,139,124-156.
7.Liang Feng,Mao-mao Zhu,Ming-hua Zhang,Ru-shang Wang,Xiao-bin Tan,Jie Song,Shu-min Ding,Xiao-bin Jia,Shao-ying Hu."Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-κB pathway activation in human umbilical vein endothelial cells,"Ethnopharmacology,2013,148,27-36.
8.Tsai-Yun Lin, Chung-Yi Chiou, Shu-Jiau Chiou."Putative Genes Involved in Saikosaponin Biosynthesis in Bupleurum Species,"Molecular Sciences,2013,14,12806-12826.
9.Yu-Chuan Huang, Wen-Liang Chang, Su-Fen Huang, Cheng-Yu Lin, Hang-Ching Lin, Tsu-Chung Chang."Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation,"Pharmacology, 2010,648,39-49.
10. Daniel K Gehlhaarl, Gennady M Verkhivker, Paul A Rejto, Christopher J Sherman I, David B Foge, Lawrence J Foge and Stephan T Freer. "Molecular recognition of the inhibitor AC-1343 by HIV-l protease: conformationally flexible docking by evolutionary programming,"Chemistry & Biology,1995,2. 11.Schneider G, Fechner U.” Computer-based de novo design of drug-like molecules,” Nature Reviews Drug Discovery,2005,4,649-63.
12.C.M. Venkatachalam, X. Jiang, T. Oldfield, M. Waldman.”LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites,” Molecular Graphics and Modelling,2003,21,289-307.
13. A.M. Jimenez-Lara, N. Clarke, L. Altucci, H. Gronemeyer.”Retinoic-acid-induced apoptosis in leukemia cells,” Trends in Molecular Medicine, 2004, 10, 508-515.
14.匡海學主編. "中藥化學," 中國中醫藥出版社, 2003, 1.
15.陳柏源主編.”生醫資料庫與藥物設計應用,” 合記圖書出版社, 2012.
16.劉景仁主編. ”癌症分子機制與標靶治療, ” 合記圖書出版社, 2012.

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔