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。中藥材小葉山葡萄科(Vitis thunbergii)，文獻證實具有抗氧化、降血脂、抑菌性等生理功能，但對於血糖調控之研究卻相當少，因此本研究探討小葉山葡萄莖之抗氧化性並評估其對醣解酵素之抑制作用，期望小葉山葡萄莖具醣解酵素抑制作用進而對糖尿病顯現改善功效。新鮮中藥材小葉山葡萄莖先以甲醇萃取，再依序利用水、正己烷、乙酸乙酯及正丁醇等溶劑進行液液萃取，並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。結果得知小葉山葡萄莖正丁醇萃取物的抗氧化及醣解酵素抑制作用較佳，此萃取物接續利用層析膠體(Amberlite XAD-7及Cosmosil 75 C18-OPN)進行區分，再以HPLC純化出4種具抗氧化及醣解酵素抑制活性之純化物質，並利用MS、UV及1H、13C-NMR推測其結構為uridine、isorhamnetin 7-O-glucoside、kaempferol 7-O-glucoside及quercetin 7-O-glucoside。

Diabetes is associated with deficiencies in insulin secretion or action. Excess reactive oxygen species are built up with chronic hyperglycemia, and are subsequently contributing to oxidative stress and related complications. Antioxidants have important roles in disorders involving oxidative stress. Glycosidases are not only involved in human digestion, but also affect the generation of many metabolic diseases such as diabetes, the most important glycosidases are α-amylase and α-glucosidase. Vitis thunbergii, has long been used in traditional Chinese medicine. Previous studies have demonstrated that V. thunbergii have antioxidant, cholesterol-lowering, antibacterial activity. However, possible roles of V. thunbergii stems on hypoglycemic regulation have not yet been explored. In the present study, antioxidative and glycosidase inhibitory components of V. thunbergii stems were identified, and their hypoglycemic activities were also investigated. V. thunbergii stems were extracted with methanol, and the methanol extract was extracted by water with n-hexane, ethyl acetate and n-butanol successively. These extracts were analysed for potential health promoting properties including their inhibitory effects on starch digestive enzymes and antioxidant activities. The n-butanol extract of V. thunbergii stems showed strong antioxidant and inhibitory properties against both α-amylase and α-glucosidase. The extract was further separated successively by Amberlite XAD-7, Comosil 75C18-OPN and reversed HPLC chromatographies to obtain four components. The isolated components were presumed to be uridine、isorhamnetin 7-O-glucoside、kaempferol 7-O-glucoside and quercetin 7-O-glucosid by MS, UV and 1H, 13C-NMR analyses.

目錄............................................................................................................I
圖目錄.......................................................................................................IV
表目錄......................................................................................................VII
附目錄.......................................................................................................VIII
中文摘要..................................................................................................IX
英文摘要...............................................................................................X
第一章、前言..............................................................................................1
第二章、文獻回顧......................................................................................2
2-1 糖尿病................................................................................................................2
2-1-1 糖尿病主要類型.............................................................................................4
2-1-2 胰島素與血糖之維持恆定………………………………………………….6
2-1-3 胰島素阻抗性與發炎反應………………………………………………….7
2-1-4 糖尿病併發症……………………………………………………………….8
2-1-5 糖尿病之治療……………………………………………………………….9
2-2 高血糖與活性氧族群……………………………………………………..…10
2-2-1活性氧族群…………………………………………………………………10
2-2-2高血糖誘導活性氧之生成機制……………………………………………13
2-2-3抗氧化系統…………………………………………………………………24
2-2-4抗氧化劑與糖尿病…………………………………………………………33
2-3高血糖與醣解酵素…………………………………………………...………35
2-3-1 α-澱粉酶與α-葡萄糖苷酶…………………………………………………35
2-3-2 醣解酵素之抑制作用對於高血糖症狀之改善…………………………...35
2-4 糖尿病之治療………………………………………………………………..38
2-5小葉山葡萄背景介紹………………………………………………………...41
2-5-1植物介紹……………………………………………………………………41
2-5-2細本山葡萄之傳統功效……………………………………………………41
2-5-3小葉山葡萄之生理活性……………………………………………………43
第三章、研究動機與實驗架構……………………………………………………..48
3-1 研究動機……………………………………………………………………..48
3-2 實驗架構……………………………………………………………………..49
第四章、材料與方法………………………………………………………………..51
4-1 實驗材料………………………………………………………………..51
4-2實驗試藥與溶劑…………………………………………………………...51
4-2-1抗氧化試驗之試藥………………………………………………………51
4-2-2醣解酵素抑制試驗之試藥………………………………………………52
4-2-3純化成分分析及光譜分析之溶劑………………………………………52
4-3實驗儀器設備………………………………………………………...52
4-4 實驗方法……………………………………………………………………..54
4-4-1 樣品萃取…………………………………………………………………...54
4-4-2水分含量測定………………………………………………………………55
4-4-3總酚含量測定(total phenolic compounds determination) ………………...55
4-4-4總類黃酮含量測定(Flavonoid determination)…………………………….56
4-4-5 DPPH自由基清除能力試驗………………………………………………56
4-4-5 ABTS自由基清除試驗(ABTS radical-scavenging assay)……………...57
4-4-6 α-amylase抑制能力測定…….………….……………………………….59
4-4-7 α-glucosidase抑制能力測定…………………………………………….59
4-4-8 小葉山葡萄莖抗氧化及醣解酵素抑制成分之萃取、分離與純化。…..60
4-4-8-1 區分I-I-I分析型高效液相層析【區分1~3】………………………...62
4-4-8-2 區分I-I-I製備型高效液相層析【區分1~3】……………………….62
4-4-8-3 區分I-I-I-2分析型高效液相層析【純化物質1、純化物質2】……...…62
4-4-8-4 區分I-I-I-2製備型高效液相層析【純化物質1、純化物質2】………...62
4-4-8-5 區分I-I-I-3分析型高效液相層析【純化物質3、純化物質4】…….…..63
4-4-8-6 區分I-I-I-3製備型高效液相層析【純化物質3、純化物質4】………...63
4-4-9 純化物質之結構鑑定……………………………………………………63
4-4-10 統計分析…………………………………………………………………64
第五章、結果……………………………………………………………………….66
5-1 小葉山葡萄莖不同溶劑萃取物之產率…………………………………….66
5-2 小葉山葡萄莖不同溶劑萃取物之總酚含量……………………………….66
5-3 小葉山葡萄莖不同溶劑萃取物之總類黃酮含量………………………….68
5-4 小葉山葡萄莖不同溶劑萃取物之抗氧化能力…………………………….68
5-5 小葉山葡萄莖不同溶劑萃取物之醣解酵素抑制活性…………………….68
5-6 小葉山葡萄莖正丁醇萃取物抗氧化及抑制醣解酵素活性成分之分離純化……72
5-6-1 小葉山葡萄莖正丁醇萃取物之第一次XAD-7液相層析……………....72
5-6-2 小葉山葡萄莖正丁醇萃取物區分I之第二次XAD-7液相層析……….76
5-6-3 小葉山葡萄莖萃正丁醇萃取物區分I-I 之Cosmosil 75 C18-OPN液相層析……80
5-6-4 小葉山葡萄莖萃正丁醇萃取物區分I-I-I之HPLC分析………………..84
5-6-5 小葉山葡萄萃正丁醇萃取物區分2之HPLC分析……………………..88
5-6-6 小葉山葡萄莖正丁醇萃取物區分3之HPLC分析……………………..90
5-7小葉山葡萄莖正丁醇萃取物純化物質之結構鑑定………………………...92
5-7-1 純化物質1之結構鑑定…………………………………………………..93
5-7-2 純化物質2之結構鑑定…………………………………………………..97
5-7-3 純化物質3之結構鑑定………………………………………………….100
5-7-4 純化物質4之結構鑑定………………………………………………….103
第六章、結論………………………………………………………………………106
第七章、參考文獻………………………………………………………………....107
第八章、附錄………………………………………………………………………121

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