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研究生:謝聖國
研究生(外文):Sheng-Kuo Hsieh
論文名稱:烏龍茶與銀杏葉中茶飢素類似物具有類飢餓素之活性分析與鑑定
論文名稱(外文):Identification and Analysis of Bioactivity of Teaghrelin-like Compounds from Oolong tea and Folium Ginkgo
指導教授:曾志正曾志正引用關係
指導教授(外文):Jason T.C. Tzen
口試委員:周濟眾陳文英李孟修郭賓崇
口試委員(外文):Chi-Chung ChouWen-Ying ChenMeng-Shiou LeePing-Chung Kuo
口試日期:2016-07-22
學位類別:博士
校院名稱:國立中興大學
系所名稱:生物科技學研究所
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:2017
畢業學年度:105
語文別:英文
論文頁數:99
中文關鍵詞:飢餓素類似物茶飢素類似物烏龍茶醯化黃酮配醣銀杏葉銀杏飢素生長激素分泌
外文關鍵詞:ghrelin analoguesteaghrelin-likeoolong teaacylated flavonoid diglycosideFolium Ginkgoginkgoghrelingrowth hormone secretion
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  • 被引用被引用:1
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  • 下載下載:34
  • 收藏至我的研究室書目清單書目收藏:2
飢餓素為近十多年來蓬勃發展的研究主題之一,各大藥廠也競相開發出各種具有模擬飢餓素活性的口服飢餓素衍生藥物,以期待能應用在各種疾病的臨床治療上。飢餓素調控人體許多的生理活性,是最主要傳遞飢餓訊息的荷爾蒙訊號分子,也直接管控生長激素分泌、間接影響體內代謝、能量平衡、記憶力、心血管與腸胃功能等生理功能。而生長激素分泌量不足被證實與人們老化生理現象有密不可分的關係。近年來在本實驗室已先後發現並且證實青心烏龍中的茶飢素與生何首烏中的首烏飢素皆具有模擬飢餓素的功能。在本研究發現可能是茶飢素合成路徑的茶飢素類似物,並且也在不同種類的烏龍茶種中發現四個茶飢素類似物。經同源模擬及分子對接進行模擬運算,依結果推論當結合香豆素的茶飢素類似物是具有潛力仿效飢餓素。此外,在銀杏葉中也發現茶飢素類似物-銀杏飢素,經實驗證明其具有飢餓素類似物(GHRP-6)相同的功能,皆能透過飢餓素受體而刺激大鼠腦下垂體前葉初代細胞分泌生長激素。依據這些天然茶激素類似物的藥學與臨床潛力,期望未來能夠發展出具有療效治療老化相關疾病且安全的口服藥物。
Ghrelin is one of the popular research topics in recent decades so that many kinds of oral ghrelin analogues are developed by pharmaceutical factories. Ghrelin analogues are expected to be used in clinical treatment of many diseases as they control many physiological functions as a major signal hormone of appetite and also because they regulate growth hormone secretion, energy homeostasis, and gastrointestinal motility. Deficiency of growth hormone secretion is one of the demonstrated ageing-related diseases among the elderly. Recently in our lab two types of compound, teaghrelins isolated from chin-shin oolong tea and emoghrelin from raw Heshouwu, were indicated to possess the functions of ghrelin analogues. This study predicts the biosynthesis of teaghrelins and identifies four teaghrelin-like compounds from other tea cultivars. The results showed that the attachment of a coumaroyl group was crucial for these teaghrelin-like compounds to bind to the ghrelin receptor by homologous modeling and docking. On the other hand, two ginkgoghrelins are also found from Folium Ginkgo. Both of these teaghrelin-like compounds with similar functions as ghrelin analogues (GHRP-6), can stimulate growth hormone secretion via GHS-R1a in primary anterior pituitary cells. Considering the pharmaceutical and clinical potential of these natural products, this study might be developed these teaghrelin-like compounds into oral ghrelin analogues.
摘要----------------------------------------------------i
Abstract-----------------------------------------------ii
List of Contents--------------------------------------iii
List of Tables and Figures------------------------------v
Abbreviation-------------------------------------------vi
Chapter I. Research Background--------------------------1
1. Growth hormone secretion-----------------------------1
2. Ghrelin----------------------------------------------1
3. Growth hormone secretagogue receptor type 1a; GHS-R1a---------------------------------------------------------5
4. Physiological function of ghrelin--------------------7
5. The developments in ghrelin receptor ligands--------13
Chapter II. Identification of biosynthetic intermediates of teaghrelins and teaghrelin-like compounds in oolong teas, and their molecular docking to the ghrelin receptor-----------------------------------------------27
1. Introduction----------------------------------------27
2. Materials and methods-------------------------------31
3. Results---------------------------------------------34
4. Discussion------------------------------------------38
Chapter III. Ginkgoghrelins, unique acylated flavonoid diglycosides in Folium Ginkgo, stimulate growth hormone secretion via activation of the ghrelin receptor-------54
1. Introduction----------------------------------------54
2. Materials and methods-------------------------------59
3. Results---------------------------------------------65
4. Discussion------------------------------------------69
Chapter IV. Conclusion---------------------------------83
Reference----------------------------------------------85
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