臺灣博碩士論文加值系統

糖尿病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，而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，亦扮演相當重要角色。中藥材薑科(Zingiberaceae)植物高良薑(Alpinia officinarum)之根莖，在先前研究證實具有良好的抗氧化、抗癌、抗炎、鎮痛、止吐等作用，但對於血糖調控之相關研究卻相當少，因此本研究探討高良薑之抗氧化性並評估對血糖調控之能力，期望高良薑對於糖尿病之改善具有潛在價值。
研究第一部分涵蓋自高良薑根莖萃取純化活性成份，進行結構鑑定及抗氧化活性分析，包括總酚類含量、總類黃酮含量、抑制脂質自氧化能力、總抗氧化能力等。從高良薑乙酸乙酯萃取物中分離出六種具有強抗氧化性之純化物質，經由可見光-紫外線吸光、液相層析質譜及核磁共振等光譜分析進行結構鑑定，其化學成分鑑定為1-hydroxy-7-(4’-hydroxy-3’-methoxyphenyl)-3-heptanone (1)、3,6-furan- 7-(4’-hydroxy-4’-methoxyphenyl) -1-phenylheptane (3) 等兩種diacryheptanoids，5,7-dihydroxy-flavanone (2)、galangin-3-methylether (4)、galangin (5)及kaempferol-4’-methylether (6)等四種類黃酮。純化物質(1-6)利用TEAC法分析總抗氧化力，結果得知其抗氧化性分別為每毫克8.55(1)、3.33(2)、7.35(3)、3.32(4)、11.46(5)及9.20(6) mM trolox當量。第二部分為血糖調控之探討，抑制α-amylase及α-glucosidase可降低碳水化合物的消化分解速率及葡萄糖吸收，減緩餐後高血糖現象。高良薑乙酸乙酯萃取物之純化物質1-6對於醣解酵素皆有不同程度的抑制效果。α-amylase抑制效果以純化物質1及4效果較佳，當樣品濃度0.1 mg/ mL，其抑制率分別為56.63及51.02%。α-glucosidase抑制效果以純化物質4及6較佳，當樣品濃度0.1 mg/ mL，其抑制率分別為25.99及28.09%。肝臟可雙向調控葡萄糖之合成及分解而為維持血糖恆定之重要臟器，流式細胞分析顯示，高糖誘導之小鼠肝臟FL83B細胞，顯著降低攝入葡萄糖類似物2-NBDG，而添加高良薑乙酸乙酯萃取物之區分C-3則顯著提高正常態及胰島素阻抗態細胞之2-NBDG攝入量，同時肝醣合成量也有增強。綜上所述，高良薑乙酸乙酯萃取物不僅具有強抗氧化性，對於血糖之調控也具有良好效果。

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 complications. Antioxidants have important roles in disorders involving oxidative stress. Rhizome of Alpinia officinarum, an herbaceous plant of Zingiberaceae family, has long been used in traditional Chinese medicine. Previous studies have demonstrated that A. officinarum have antioxidant, anticancer, anti-nociceptive, anti-inflammatory and antiemetic activities. However, possible roles of A. officinarumin hypoglycemic regulation have not yet been explored. In the present study, antioxidative components of A. officinarumwere identified, and their hypoglycemic activitieswere then investigated.
The first part of this study covered extraction, fractionation, and structural analysis of active compoundsfrom A. officinarum rhizome. Corresponding antioxidant activities were then determined, including total phenolic content, total flavonoid content, ferric thiocyanate assay and trolox equivalent antioxidant capacity. Six compounds with strong antioxidant activity were obtained (1-6) from ethyl acetate extract of A. officinarum rhizome by using silica gel, XAD-2 and HPLC chromatographies and their structure identified by UV-visible spectrometry, liquid chromatography-mass spectra, 1H and 13C-NMR instrumental analyses. The isolated components were identified to be two diacryheptanoids, 1-hydroxy-7-(4’-hydroxy-3’-methoxyphenyl)-3- heptanone (1), and 3,6-furan-7-(4’-hydroxy-4’-methoxyphenyl)-1- phenylheptane (3) and four flavonols, 5,7-dihydroxy-flavanone (2), galangin-3-methylether (4), galangin (5), and kaempferol-4’-methylether (6). The antioxidant activity of components 1-6 was 8.55(1), 3.33(2), 7.35(3), 3.32(4), 11.46(5) and 9.20(6) mM trolox equivalent. In the second part of this study, possible hypoglycemic activities of A. officinarum rhizome were examined. Inhibiting α-amylase and α-glucosidase may delay breaking carbohydrates into glucose, there by suppress postprandial hyperglycemia. Among six components isolated from A. officinarum rhizome, compound 1 and 4 gave the highest inhibition rates against α-amylase, which were 56.63 and 51.02% respectively. Compound 4 and 6 were most efficient in inhibiting α-glucosidase, with inhibition rates of 25.99 and 28.89%. Liver plays pivotal roles in glucose homeostasis by regulating glucose metabolism and mobilization. As revealed by flow cytometry, treating murine FL83B hepatocytes with high concentration of glucose significantly reduced the uptake of glucose analogue 2-NBDG. C-3 fraction of acetyl acetate extract of A. officinarum rhizome restored 2-NBDG uptake of FL83B cells under normal or insulin resistant states. Concurrent increase of glycogen content suggested that glycogen synthesis was also enhanced by the acetyl acetate extract. Our results indicate that the acetyl acetate extract of A. officinarum rhizome possesses profound antioxidant and hypoglycemic activities in vitro.

目錄...................................................................................................I
圖目錄..................................................................................................V
表目錄.................................................................................................IX
附目錄..................................................................................................X
中文摘要..............................................................................................XI
英文摘要.............................................................................................XIII
第一章、前言............................................................................................1
第二章、文獻回顧.........................................................................................2
2-1 高良薑背景介紹.......................................................................................2
2-1-1 植物介紹..........................................................................................2
2-1-2 高良薑之傳統功效...................................................................................2
2-1-3 高良薑之生理活性...................................................................................3
2-2 糖尿病..............................................................................................5
2-2-1 糖尿病主要類型.....................................................................................7
2-2-2胰島素與血糖之維持恆定...............................................................................9
2-2-3 胰島素抗性.......................................................................................10
2-2-4 以細胞模式探討胰島素阻抗性之改善....................................................................10
2-3 高血糖與活性氧族群..................................................................................12
2-3-1活性氧族群........................................................................................12
2-3-2 高血糖誘導活性氧之生成機制.........................................................................15
2-3-3 抗氧化系統.......................................................................................26
2-3-4抗氧化劑與糖尿病...................................................................................35
2-4 高血糖與醣解酵素....................................................................................37
2-4-1 α-澱粉酶與α-葡萄醣苷酶............................................................................37
2-4-2醣解酵素活性之抑制對於高血糖之改善...................................................................37
2-5 糖尿病之治療.......................................................................................40
第三章、研究動機與實驗架構...............................................................................43
3-1 研究動機...........................................................................................43
3-2 實驗架構...........................................................................................44
第四章、材料與方法......................................................................................45
4-1 實驗材料...........................................................................................45
4-2 實驗試藥與溶劑......................................................................................45
4-2-1 抗氧化試驗之試藥..................................................................................45
4-2-2 酵素試驗之試藥....................................................................................45
4-2-3 細胞培養之試藥....................................................................................46
4-2-4 成分分析試驗之溶劑................................................................................46
4-3 實驗設備...........................................................................................47
4-3-1 化學試驗之儀器設備................................................................................47
4-3-2細胞測定之儀器設備.................................................................................47
4-4 實驗方法...........................................................................................48
4-4-1 樣品萃取.........................................................................................48
4-4-2 總酚含量測定.....................................................................................49
4-4-3總類黃酮含量測定...................................................................................49
4-4-4 硫氰酸鐵法測定....................................................................................50
4-4-5 總抗氧化能力測定..................................................................................51
4-4-6 抗氧化成分之萃取、分離及純化.......................................................................51
4-4-7 α-amylase抑制能力測定............................................................................55
4-4-8 α-glucosidase抑制能力測定........................................................................56
4-4-9細胞培養..........................................................................................57
4-4-10 XTT assay細胞毒性測定...........................................................................58
4-4-11 FL83B細胞之葡萄糖擬似物2-NBDG攝入量分析...........................................................59
4-4-12細胞內肝醣合成量分析..............................................................................62
4-4-13蛋白質定量.......................................................................................62
4-4-14統計分析.........................................................................................63
第五章、結果...........................................................................................64
5-1 高良薑乙酸乙酯萃取物抗氧化成分之分離純化...............................................................64
5-1-1 高良薑萃取物之產率................................................................................64
5-1-2 高良薑萃取物之總酚類化合物含量......................................................................64
5-1-3 高良薑萃取物之總類黃酮含量.........................................................................64
5-1-4 高良薑萃取物之脂質自氧化抑制能力....................................................................66
5-1-5 高良薑乙酸乙酯萃取物抗氧化成分之分離與純化...........................................................68
5-1-5-1乙酸乙酯萃取物之矽膠液相管柱層析...................................................................68
5-1-5-2 區分物C之XAD-2液相管柱層析......................................................................68
5-1-5-3 區分物C-3之HPLC分析............................................................................72
5-1-5-4 純化物質之結構鑑定..............................................................................77
5-1-5-5 高良薑乙酸乙酯萃取物之純化物質抗氧化性............................................................105
5-2高良薑乙酸乙酯萃取物區分物及純化物質之調節血糖作用......................................................107
5-2-1高良薑乙酸乙酯萃取物純化物質對於醣解酵素之抑制效果....................................................107
5-2-1-1純化物質對α-amylase之抑制作用...................................................................107
5-2-1-2純化物質對α-glucosidase之抑制作用...............................................................107
5-2-2 高良薑乙酸乙酯萃取物區分C-3對FL83B細胞之調節血糖作用................................................109
5-2-2-1 高良薑乙酸乙酯萃取物區分C-3對於FL83B細胞之毒性....................................................109
5-2-2-2不同濃度區分C-3對於正常態FL83B細胞之2-NBDG攝入量之影響.............................................111
5-2-2-3 20ppm區分C-3對於正常及胰島素阻抗性FL83B細胞之2-NBDG攝入量之影響...................................111
5-2-2-4高良薑乙酸乙酯萃取物區分C-3對於FL83B細胞內肝醣合成量之影響..........................................112
第六章、討論..........................................................................................116
6-1 高良薑抗氧化性比較.................................................................................116
6-2 高良薑對醣解酵素抑制作用............................................................................117
6-3 高良薑對胰島素阻抗之改善............................................................................119
6-4 綜合討論..........................................................................................120
第七章、結論..........................................................................................123
第八章、參考文獻.......................................................................................124
第九章、附錄..........................................................................................138

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