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研究生:陳元孝
研究生(外文):Chen, Yuan-Siao
論文名稱:左手香抗發炎成分及其衍生物研究
論文名稱(外文):Chemical Constituents of Plectranthus amboinicus and Synthetic Analogs as Anti-inflammation Agents
指導教授:翁啟惠翁啟惠引用關係余惠敏余惠敏引用關係
指導教授(外文):Wong, Chi-HueyYu, Hui-Ming
口試委員:吳宗益方俊民李水盛張嘉銓
口試委員(外文):Wu, Chung-YiFang, Jim-MinLee, Shoei-ShengChang, Chia-Chuan
口試日期:2014-05-07
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
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:99
中文關鍵詞:左手香
外文關鍵詞:Plectranthus amboinicus
相關次數:
  • 被引用被引用:3
  • 點閱點閱:2007
  • 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:272
  • 收藏至我的研究室書目清單書目收藏:1
左手香是傳統藥用植物,常被用在治療發炎相關疾病。近來研究結果顯示左手香對膠原蛋白誘發關節炎的小鼠有治療效果,但其中有效成分仍然未知。Activator protein 1 (AP-1)是細胞內重要的轉錄因子,其活性被發現與發炎反應相關,針對AP-1結構設計的抑制劑對膠原蛋白誘發關節炎的小鼠有治療效果。Tumor necrosis factor α (TNF-α)是發炎反應中一個重要的細胞激素,目前TNF-α的單株抗體以及接受體融合蛋白質已經被美國食品暨藥物管制局認可成為類風溼性關節炎的臨床用藥。為了找出左手香治療關節炎的有效成分,我們使用高效液相色譜法將左手香莖葉汁做分離收集,對於AP-1活性有抑制效果的區段進一步分離鑑定,我們鑑定出shimobashiric acid C (2)、salvianolic acid L (3)、rosmarinic acid (4), 以及新穎化合物mena987 (1)。另外我們發現左手香的低極性萃取物分別對於TNF-α以及膠原蛋白誘發關節炎的小鼠有良好的抑制及治療效果,我們利用矽膠製備的液相層析管柱分離左手香的低極性萃取物,鑑定出thymoquinone為抑制TNF-α的活性化合物。針對thymoquinone的結構我們設計出活性更強的TNF-α抑制劑cyclopent-4-ene-1,3-diones 6a、6b、6d與6f。
Plectranthus amboinicus is a traditional herbal medicine that has been used for decades to treat inflammation-related diseases. Recent studies have shown that it also has a therapeutic effect in a collagen-induced arthritis animal model. Activator protein 1 (AP-1) activity has been reported to be correlated with inflammation, and designed AP-1 inhibitors have a therapeutic effect in an arthritis animal model. Tumor necrosis factor α (TNF-α) is a key cytokine in inflammation and is the target of FDA-approved rheumatoid arthritis drugs. In our study, HPLC fractions of P. amboinicus leaf juice were examined for inhibitory activity in an in vitro AP-1 binding consensus DNA sequence, resulting in the identification of shimobashiric acid C (2), salvianolic acid L (3), rosmarinic acid (4), and a novel compound, mena987 (1). The nonpolar ingredients from the hexane extract of P. amboinicus leaf juice suppress the lipopolysaccharide-induced TNF-α expression and joint destruction of CIA mouse model. We identified thymoquinone as active compound based on TNF-α inhibition assay. The synthetic cyclopent-4-ene-1,3-diones 6a, 6b, 6d and 6f are even more potent TNF-α inhibitors.
正文目錄

中文摘要 ………………………………………………………………….V
Abstract …………………………………………………….……….VI
Introduction …………………………………………………………1
Materials and Methods ………………….……………7
Results ………………………………………………………………………22
Discussion …………………………………………………………..30
Conclusion …………………………………. ………………………35
Figures and Tables ……………………………………….36
Reference ……………………………………. …………………..57

圖目錄

Figure 1. ……………………………………………………………………..36
Figure 2. ……………………………………………………………………..38
Figure 3. ……………………………………………………………………..39
Figure 4. ……………………………………………………………………..40
Figure 5. ……………………………………………………………………..41
Figure 6. …………………………………………………………. ………….43
Figure 7. ……………………………………………………………………..44
Figure 8. ……………………………………………………………………..45
Figure 9. ……………………………………………………………………..46
Figure 10. ……………………………………………………………………..47
Figure 11. ……………………………………………………………………..48
Figure 12. ……………………………………………………………………..49
Figure 13. ……………………………………………………………………..50
Figure 14. ……………………………………………………………………..51
Figure 15. ……………………………………………………………………..53
Figure 16. ……………………………………………………………………..54
Figure 17. ……………………………………………………………………..56

附錄目錄

附錄1. 1H NMR spectrum of compound 1 (600 MHz, D2O)
附錄2. 13C NMR spectrum of compound 1 (150 MHz, D2O)
附錄3. 1H NMR spectrum of compound 2 (600 MHz, D2O)
附錄4. 13C NMR spectrum of compound 2 (150 MHz, D2O)
附錄5. 1H NMR spectrum of compound 3 (600 MHz, D2O)
附錄6. 13C NMR spectrum of compound 3 (150 MHz, D2O)
附錄7. 1H NMR spectrum of compound 4 (600 MHz, D2O)
附錄8. 13C NMR spectrum of compound 4 (150 MHz, D2O)
附錄9. 1H NMR spectrum of compound 5 (600 MHz, CDCl3)
附錄10. 13C NMR spectrum of compound 5 (150 MHz, CDCl3)
附錄11. 1H NMR spectrum of compound 6a (600 MHz, CDCl3)
附錄12. 13C NMR spectrum of compound 6a (150 MHz, CDCl3)
附錄13. 1H NMR spectrum of compound 6b (600 MHz, CDCl3)
附錄14. 13C NMR spectrum of compound 6b (150 MHz, CDCl3)
附錄15. 1H NMR spectrum of compound 6c (600 MHz, CDCl3)
附錄16. 13C NMR spectrum of compound 6c (150 MHz, CDCl3)
附錄17. 1H NMR spectrum of compound 6d (600 MHz, CDCl3)
附錄18. 13C NMR spectrum of compound 6d (150 MHz, CDCl3)
附錄19. 1H NMR spectrum of compound 6e (600 MHz, CDCl3)
附錄20. 13C NMR spectrum of compound 6e (150 MHz, CDCl3)
附錄21. 1H NMR spectrum of compound 6f (600 MHz, CDCl3)
附錄22. 13C NMR spectrum of compound 6f (150 MHz, CDCl3)


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