臺灣博碩士論文加值系統

糖尿病(diabetes mellitus)與胰島素分泌不足或作用缺失相關。高血糖使體內產生過多活性氧，造成氧化壓力上升及相關併發症發生，抗氧化物質對於活性氧所引發疾病之調控中扮演重要角色。而醣解酵素不但參與人體消化作用，也影響許多代謝疾病如糖尿病的產生，醣解酵素中以α-澱粉酶(α-amylase)及α-葡萄醣苷酶(α-glucosidase)最為重要。中藥材金銀花(Lonicera japonica Thunb.)屬於忍冬科 (Caprifoliaceae) 忍冬屬 (Lonicera)植物，文獻證實具有抗菌、抗病毒、抗發炎、保護神經細胞、抗氧化、保肝等生理功能，但對於血糖調控之研究卻相當少，因此本研究探討金銀花之抗氧化性並評估其對醣解酵素之抑制作用，期望金銀花具醣解酵素抑制作用進而對糖尿病具改善功效。金銀花乾燥全草先以甲醇萃取，再依序利用正己烷、乙酸乙酯及正丁醇等溶劑進行液液萃取，各溶劑區分物以抗氧化及醣解酵素抑制活性為篩選平台，進行活性成分之分離、純化及結構鑑定。結果得知金銀花乙酸乙酯區分物的抗氧化及醣解酵素抑制作用較佳，此區分物利用層析膠體(Amberlite XAD-7 及Cosmosil 75 C18-OPN)進行區分，評估區分物之抗氧化及醣解酵素抑制活性，並利用 1H-NMR 對乙酸乙酯區分物進行成分分析以及結構鑑定，因純化量甚微，無法取得足夠光譜資訊，所以直接利用液相層析串聯質譜法 (LC-MS/MS)進行乙酸乙酯區分物活性成分之純化及比對分析，目前已鑑定出主要活性成分為3種咖啡醯奎寧酸之多酚類化合物(phenyl ethanoid glycosides)，分別為 5-O-caffeoylquinic acid (1)、3,5-di-O-caffeoylquinic acid (2) 及 4,5-di-O-caffeoylquinic acid (3)。根據抗氧化及醣解酵素抑制作用測試、LC-MS/MS 結構鑑定以及參考過去文獻，推測金銀花抗氧化及醣解酵素抑制作用之活性物質主要可能來自上述咖啡醯奎寧酸衍生物之多酚類化合物。

Diabetes is associated with deficiencies in insulin secretion or activity.
Excess reactive oxygen species are building up with chronic hyperglycemia, and are subsequently contributing to oxidative stress and complications. Antioxidants have important roles in disorders involving oxidative stress. Glycosidases are not only involved in human digestion, but also affect the occurring of many metabolic diseases such as diabetes. The most important glycosidases in human digest system are α-amylase and α-glucosidase. Lonicera japonica Thunb., is an herbaceous plant of Caprifoliaceae family. Previous studies have demonstrated that Lonicera japonica Thunb. has antibacterial activity, antiviral activity, anti-inflammatory, neuroprotective, antioxidative and hepatoprotective activities. However, possible roles of Lonicera japonica Thunb. in hypoglycemic regulation have not yet been explored. In the present study, glycosidases inhibitions of Lonicera japonica Thunb. were investigated.
Lonicera japonica Thunb. was extracted with methanol first, and then methanol extracts were extracted by water with n-hexane, ethyl acetate and n-butanol successively. These extracts were analysed for their potential health promoting properties including their inhibitory effect on starch digestive enzymes and antioxidant activities. Ethyl acetate extract of Lonicera japonica Thunb. showed better antioxidant and inhibitory properties against α-glucosidase. The extract was further separated successively by Amberlite XAD-7, Comosil 75C18-OPN and reversed HPLC to obtain five components. Due to the contents of isolated components were too little to get enough spectral information for 1H-NMR, by using liquid chromatography tandem-mass spectrometry( LC-MS/MS), the components from ethyl acetate fraction were identified to be three caffeoylquinic acids: 5-O-caffeoylquinic acid (1), 3,5-di-O-caffeoylquinic acid (2) and 4,5-di-O-caffeoylquinic acid (3). Based on antioxidant test and glycosidase inhibition, LC-MS / MS structure identification and reference from literature, the active substances of Lonicera japonica Thunb. for antioxidation and glycosidase inhibition may be mainly derived from polyphenolic compounds of the caffeoylquinic acids.

目錄
目錄-----------------------------------------------------------------------Ⅰ
圖目錄---------------------------------------------------------------------Ⅳ
表目錄---------------------------------------------------------------------Ⅵ
附目錄---------------------------------------------------------------------Ⅶ
中文摘要-------------------------------------------------------------------Ⅷ
英文摘---------------------------------------------------------------------X
壹、前言-------------------------------------------------------------------1
貳、文獻回顧---------------------------------------------------------------3
一、金銀花----------------------------------------------------------------3
(一)金銀花之介紹--------------------------------------------------------3
(二)金銀花之傳統功效-----------------------------------------------------4
(三)金銀花之生理活性-----------------------------------------------------4
二、糖尿病----------------------------------------------------------------12
(一)胰島素(Insulin)-----------------------------------------------------15
(二)糖尿病主要類型-------------------------------------------------------19
(三)糖尿病症狀及所引起之併發症--------------------------------------------23
(四)糖尿病之治療---------------------------------------------------------26
(五)高血糖與醣解酵素-----------------------------------------------------29
(六)醣解酵素活性的抑制對高血醣症狀之改善-----------------------------------30
三、高血糖與自由基之關聯----------------------------------------------------33
(一)自由基與活性氧之種類--------------------------------------------------33
(二)自由基與活性氧之來源--------------------------------------------------36
(三)自由基與活性氧對生物體之影響------------------------------------------36
四、脂質氧化作用-----------------------------------------------------------38
(一)起始期 ( initiation stage )-----------------------------------------38
(二)連鎖增殖期( propagation stage )-------------------------------------39
(三)終止期 ( termination stage )----------------------------------------39
五、抗氧化作用-------------------------------------------------------------42
(一)抗氧化作用機制-------------------------------------------------------42
(二)天然抗氧化劑---------------------------------------------------------45
(三)人工合成抗氧化劑-----------------------------------------------------58
(四)體內酵素性抗氧化作用-------------------------------------------------61
六、液相層析串聯質譜法(Liquid chromatography tandem-mass spectrometry,LC-MS/MS)-64
(一)液相層析串聯質譜法簡介-----------------------------------------------64
(二)串聯式質譜法(tandem mass spectrometry, MS/MS)-----------------------66
(三)液相層析串聯質譜儀運用-----------------------------------------------66
(四)液相層析串聯質譜儀分析藥食同源植物有效成分之運用-----------------------67
(五)質譜儀運用於殘留農藥及動物用藥之檢驗----------------------------------70
參、研究目的與實驗流程------------------------------------------------------72
一、研究目的--------------------------------------------------------------72
二、實驗架構--------------------------------------------------------------73
肆、材料與方法-------------------------------------------------------------74
一、實驗材料--------------------------------------------------------------74
(一)樣品---------------------------------------------------------------74
(二)實驗試藥與溶劑------------------------------------------------------74
(三)實驗儀器設備--------------------------------------------------------76
二、實驗方法--------------------------------------------------------------78
(一)萃取樣品------------------------------------------------------------78
(二)總酚含量測定(total phenolic compounds determination)----------------79
(三)總類黃酮含量測定(Flavonoid determination)---------------------------79
(四) DPPH自由基清除能力試驗---------------------------------------------80
(五)總抗氧化能力測定(Trolox equivalent antioxidant capacity, TEAC) ----81
(六)α-amylase 抑制作用測定------------------------------------------------81
(七)α-glucosidase抑制作用測定---------------------------------------------83
(八)金銀花抗氧化及醣解酵素抑制成分之萃取、分離與純化-------------------------83
(九)液相層析串聯質譜儀(Liquid chromatography tandem-mass spectrometry, LC-MS/MS)-86
(十)統計分析--------------------------------------------------------------88
伍、結果與討論------------------------------------------------------------89
一、金銀花溶劑區分物之產率------------------------------------------------89
二、金銀花各種溶劑區分物之總酚含量----------------------------------------90
三、金銀花各種溶劑區分物之總類黃酮含量-------------------------------------90
四、金銀花各種溶劑區分物之DPPH自由基清除能力-------------------------------92
五、金銀花各種溶劑區分物總抗氧化能力測定-----------------------------------93
六、金銀花各種溶劑區分物對醣解酵素之抑制活性-------------------------------94
七、金銀花乙酸乙酯區分物抗氧化及抑制醣解酵素活性成分之分離純化---------------96
(一)XAD-7 液相管柱層析--------------------------------------------------96
(二)金銀花乙酸乙酯區分物區分(III)之第一次 Cosmosil 75 C18-OPN 液相管柱層析-102
(三)金銀花乙酸乙酯區分物區分(C)之第二次 Cosmosil 75 C18-OPN 液相管柱層析---108
(四)金銀花乙酸乙酯區分物區分a、b、c、d 之 HPLC 分析及製備------------------110
(五)金銀花乙酸乙酯區分物區分物 LC-MS/MS 之分離純化及比對分析---------------116
(六)金銀花乙酸乙酯區分物純化物質之結構鑑定-------------------------------124
陸、結論----------------------------------------------------------------128
柒、參考文獻------------------------------------------------------------129
捌、附錄----------------------------------------------------------------136

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