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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔣丙煌(Been-Huang Chiang) | |
dc.contributor.author | Yu-Zhu Huang | en |
dc.contributor.author | 黃郁筑 | zh_TW |
dc.date.accessioned | 2021-06-08T04:49:13Z | - |
dc.date.copyright | 2009-07-31 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-28 | |
dc.identifier.citation | 李時珍著; 劉衡如、劉山永校著。2002。本草綱目。華夏出版社。北京。頁數
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23239 | - |
dc.description.abstract | 糖尿病 (diabetes mellitus) 近十年來位居台灣地區十大死因之ㄧ,第二型糖尿病的主要症狀為長期性高血糖,長期性高血糖會使體內氧化壓力增加,並常伴隨高度糖化產物 (advanced glycation end products; AGEs) 濃度過高及對胰島素敏感的週邊細胞葡萄糖攝入能力較差等現象。
傳統上第二型糖尿病用藥仍存在許多副作用,最新的治療方式是藉由抑制dipeptidyl peptidase-4 (DPP-4) 此酵素來達到調節血糖之目的,DPP-4 會使 GLP-1 (glucagon-like peptide-1) 失活,GLP-1 是種腸道荷爾蒙,可依血糖濃度來促進胰島素分泌或抑制昇糖素釋出,而達到降血糖的功效,且不會有血糖過低的副作用。目前 DPP-4 抑制劑皆由化學合成,本研究嘗試以抑制 DPP-4 為篩選平台從天然物中找尋具預防與改善糖尿病症的物質。 先從本草綱目中選出用於治療消渴症之六種中藥材,再從已知的科學文獻中選出富含 lignan 之三種天然物。實驗發現在九種天然物中,五倍子 (Galla chinensis) 經由 121℃,60 分鐘熱水萃取,其萃出液具有抑制 DPP-4 的能力 (100 μg/mL 濃度下,抑制率為 49.6 ± 2.3%)。再以 Sephadex LH-20 膠體將熱水萃取物分離成 A~J 共 10 個區分物,將區分物與熱水萃取物進行抗氧化試驗 (清除 DPPH 自由基、抑制由銅離子誘導人類 LDL 氧化)、DPP-4 抑制實驗、改善糖尿病症狀相關試驗 (抑制AGEs 形成、刺激細胞葡萄糖攝入) 來檢測其抗糖尿病活性。結果顯示,在抗氧化與改善糖尿病症狀此四個實驗中,G 區分物皆展現良好之活性,其具有清除 DPPH 自由基能 (IC50= 52.9 ± 0.5 μg/mL)、延緩銅離子誘導 LDL 氧化效果為同濃度下正控制組 (trolox) 之 1.7 倍、抑制 AGEs 形成能力與正控制組 (quercetin) 相當、促進胰島素抗性細胞吸收 2.5 ± 0.4 倍葡萄糖,具有改善細胞胰島素抗性的能力。在 DPP-4 抑制實驗中,J、H、I 區分物展現的活性較其他區分物佳 (100 μg/mL 濃度下,抑制率為 49.6 ± 2.3% ~ 57.8 ± 2.0%)。因此,針對 G、H、I、J 區分物進行高效液相層析儀分析,收集各區分物中主要成分波峰,以質譜儀檢測分子量與分子離子峰,將數據與文獻進行比對。得知,G 區分物中主要成分可能為 methyl gallate 與 digallic acid; H 區分物主要成分可能為 1,2,6-tri-O-galloyl-β-d-glucose;I 區分物中主要成分可能為 1,2,3,6-tetra-O-galloyl-β-d-glucose;J 區分物中主要成分可能為1,2,3,4,6-penta-O-galloyl-β-d-glucose。 本實驗為第一次發現具有抑制 DPP-4 之天然物,並推知其主要的活性成分極有可能為 1,2,6-tri-O-galloyl-β-d-glucose、1,2,3,6-tetra-O-galloyl-β-d-glucose、 1,2,3,4,6-penta-O-galloyl-β-d-glucose,但須進一步以 NMR 或 IR 確認活性成分結構。综合以上實驗結果,可知五倍子具有抑制 DPP-4、清除 DPPH 自由基、延緩銅離子誘導人類 LDL 氧化、抑制 AGEs 形成、刺激細胞吸收葡萄糖等各種生理活性,全方面性具有改善及預防糖尿病及其併發症之功效,具有發展為抗糖尿病活性產品之潛力。 | zh_TW |
dc.description.abstract | Diabetes mellitus is one of the ten leading causes of death in Taiwan. Chronic hyperglycemic is the main symptom of type 2 diabetes, and it not only increases body oxidative stress but also accumulates advanced glycation end products (AGEs) and causes the insulin sensitive cells to decrease glucose uptake ability.
There is still limitation in current available therapeutic treatments for type 2 diabetes. A novel approach to treat type 2 diabetes is using DPP-4 inhibitors to improve the duration of endogenous GLP-1 (Glucagon-like peptide-1) activity. GLP-1 is a gut hormone, it stimulates the secretion of insulin and inhibits glucagon release in a glucose dependent manner. This decreases the glycemic excursion, and would not cause hypoglycemic side effect. Until now, all of DPP-4 inhibitors are chemically synthesized. Hence, we tried to use DPP-4 inhibition as a model to find out the materials from nature substances which are able to prevent and improve the conditions of diabetic patients. The results of the study showed that hot water extract of Galla chinensis at 121℃ for 60 min was able to inhibit DPP-4 activity (inhibition ratio is 49.6 ± 2.3% at 100 μg/mL ). Furthermore, the hot water extract was separated by Sephadex LH-20 into A~J fractions. All fractions and hot water extract were examined by antioxidative assays (DPPH free radical scavenging effect and inhibition of Cu2+-induced oxidation of human low-density lipoprotein assay), DPP-4 inhibition assay, and diabetes symptoms related assays (inhibit AGEs formation, stimulate cells glucose uptake ability) for their anti-diabetes abilities. It was found that G fraction had the superior IC50 of antioxidant activity and showed positive effect during diabetes symptoms related assays. It’s DPPH free radical scavenging activity was 52.9 ± 0.5 μg/mL, the delaying LDL oxidation effect was 1.7 times better than Trolox at the same concentration (0.5 μg/mL), it’s ability of inhibiting AGEs formation is the same with positive control quercetin at the same concentration (20 μg/mL), it stimulates insulin resistant cells uptake glucose 2.5 ± 0.4 times, improving glucose uptake of the insulin resistance cells. In DPP-4 inhibition assay, J, H, I fractions are better than other fractions (Inhibition ratio are 49.6 ± 2.3% ~ 57.8 ± 2.0% at 100 μg/mL). Consequently, we purified G、H、I、J fractions via High Performance Liquid Chromatography and identified their molecular weights by Mass Spectrometry. The mass spectra data were compared with the data in literatures, and indicated that major compounds in G fraction were methyl gallate and digallic acid. While, H, I, J fractions maybe 1,2,6-tri-O-galloyl-β-d-glucose, 1,2,3,6-tetra-O-galloyl-β-d-glucose, 1,2,3,4,6-penta-O-galloyl-β-d-glucose, respectively. To the best of our knowledge is the first time that DPP-4 inhibitors is discovered from nature substances, and the active compounds probably are 1,2,6-tri-O-galloyl-β-d-glucose、1,2,3,6-tetra-O-galloyl-β-d-glucose、 1,2,3,4,6-penta-O-galloyl-β-d-glucose. However, the chemical structures of these compounds should be further identified by NMR and/or IR. This study showed that Galla chinensis is able to inhibit DPP-4 activity, scavenges DPPH free radical, delays Cu2+-induced oxidation of human LDL, and stimulates insulin resistant cells uptake glucose. Thus, it is able to prevent and improve the conditions of diabetic symptoms via different ways. Therefore, Galla chinensis has potential to be developed as an anti-diabetes products. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:49:13Z (GMT). No. of bitstreams: 1 ntu-98-R96641015-1.pdf: 1483032 bytes, checksum: 66f3d94707863d730931635965613379 (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 謝誌................................................................................................................................I
中文摘要.......................................................................................................................II 英文摘要 IV 圖次 IX 表次 XI 詞彙縮寫表 XII 壹、文獻回顧 1 一、糖尿病 1 (一)糖尿病的定義與診斷依據 1 (二)糖尿病的分類 2 1. 第一型糖尿病 2 2. 第二型糖尿病 2 3. 專一型糖尿病 2 4. 妊娠糖尿病 2 (三)高血糖對人體的影響 4 1. 高血糖與自由基形成 4 2. 高血糖與 AGEs 形成之關係 6 (四)糖尿病用藥 7 1. 促進胰島素分泌 7 2. 改善胰島素阻抗性 7 3. 減緩碳水化合物吸收 8 二、Incretin-based therapy 9 (一) Incretin-based therapy 9 (二) Incretin.. 10 1. The incretin effect 10 2. GLP-1 與 GIP 的生理作用 11 (三) Dipeptidyl Peptidase-4 13 1. DPP-4 的分佈 13 2. DPP-4 之生理功能 14 (四)以抑制 DPP-4 作為治療第二型糖尿病之研究 14 1.老鼠試驗中 DPP-4 抑制之研究 14 2.DPP-4 基因剔除鼠試驗 15 3.人體試驗中 DPP-4 抑制之研究 15 4.以抑制 DPP-4 作為治療第二型糖尿病之優點............................16 5.化學合成之 DPP-4 抑制劑 16 三、五倍子 17 (一)五倍子 17 (二)五倍子分佈 17 (三)五倍子於古籍中之記載 17 (四)五倍子之生理活性 18 1. 抑制 α-glucosidase 活性 18 2. 抗氧化、抗菌活性 18 3. 抗腹瀉活性 18 4. 抑制酪胺酸酶活性 19 5. 抗肝炎病毒活性 19 (五)五倍子成分 19 1. Gallotannin 20 2. Phenolics 20 3. Flavonoids 22 4. Triterpene 23 5. Steroids 24 貳、研究目的與實驗架構 25 第一部份 25 一、研究目的 25 二、實驗架構 26 第一部分之一、從天然物中尋找具有抑制 DPP-4 活性之物質 26 第一部分之二、探討五倍子中已知純化合物對 DPP-4 的抑制能力 27 第二部份 28 一、研究目的 28 二、實驗架構 28 第二部分之一、探討五倍子萃取條件對 DPP-4 抑制能力之影響 28 第二部分之二、探討五倍子萃取條件對萃取物中總酚、總類黃酮含量變化 29 第三部份 30 一、研究目的 30 二、實驗架構 30 第三部分之一、Sephadex LH20 膠體分離五倍子熱水萃取物 30 第三部分之二、五倍子熱水萃取物 A~J 區分物抗糖尿病活性實驗與總酚、總類黃酮含量分析 31 第三部分之三、五倍子熱水萃取物 A~J 區分物主要成分分析 32 参、材料與方法 33 一、材料來源 33 二、第一部份實驗方法與儀器藥品 33 (一)中藥材熱水萃取物製備 33 (二)抑制 DPP-4 酵素試驗 34 三、第二部份實驗方法與儀器藥品 35 (一)五倍子熱水萃取物製備 35 (二)總酚類含量測定 36 (三)總類黃酮含量測定 37 四、第三部份實驗方法與儀器藥品 39 (一)五倍子熱水萃取物管柱分離方法 39 (二)清除 DPPH 自由基實驗 41 (三)銅離子誘導人類低密度脂蛋白氧化實驗 42 (四)高度糖化終產物形成實驗 45 (五)葡萄糖攝入實驗 47 (六)高效能液相層析儀分析 50 (七)電噴灑游離質譜分析 51 五、數據分析 51 肆、結果與討論 52 一、第一部份 52 (一)從天然物中尋找具有抑制 DPP-4 活性之物質 52 (二)探討五倍子中已知純化合物對 DPP-4 的抑制能力 54 二、第二部份 57 (一)探討五倍子萃取條件對 DPP-4 抑制能力之影響 57 (二)探討五倍子萃取條件對萃取物中總酚、總類黃酮含量變化 60 三、第三部份 67 (一)Sephadex LH20 膠體分離五倍子熱水萃取物 67 (二)五倍子熱水萃取物A~J區分物抗糖尿病活性實驗與總酚、總類黃酮含量分析 74 (三)五倍子熱水萃取物 A~J 區分物主要成分分析 91 (四)综合討論 106 伍、結論 108 陸、參考文獻 110 附錄…………………………………………………………………………………119 | |
dc.language.iso | zh-TW | |
dc.title | 五倍子對第二型糖尿病預防及改善之研究 | zh_TW |
dc.title | Effect of Galla chinensis on prevention and improvement of type 2 diabetes mellitus | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 沈立言,莊明恆 | |
dc.subject.keyword | 糖尿病,DPP-4,GLP-1,五倍子,Gallotannin,1,2,6-tri-O-galloyl-β-d-glucose,1,2,3,6-tetra-O-galloyl-β-d-glucose,1,2,3,4,6-penta-O-galloyl-β-d-glucose, | zh_TW |
dc.subject.keyword | diabetes mellitus,DPP-4,GLP-1,Galla chinensis,Gallotannin,1,2,6-tri-O-galloyl-β-d-glucose,1,2,3,6-tetra-O-galloyl-β-d-glucose,1,2,3,4,6-penta-O-galloyl-β-d-glucose, | en |
dc.relation.page | 133 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2009-07-28 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 食品科技研究所 | zh_TW |
顯示於系所單位: | 食品科技研究所 |
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