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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 孫璐西 | |
| dc.contributor.author | Wen-Chien Lu | en |
| dc.contributor.author | 呂玟蒨 | zh_TW |
| dc.date.accessioned | 2021-06-13T03:22:35Z | - |
| dc.date.available | 2016-08-02 | |
| dc.date.copyright | 2011-08-02 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-07-29 | |
| dc.identifier.citation | Appeldoorn, M. M., Vincken, J. P., Aura, A. M., Hollman, P. C., & Gruppen, H. (2009). Procyanidin dimers are metabolized by human microbiota with 2-(3,4-dihydroxyphenyl) acetic acid and 5-(3,4-dihydroxyphenyl)-gamma- valerolactone as the major metabolites. J Agric Food Chem, 57(3), 1084-1092.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/31863 | - |
| dc.description.abstract | 龍眼 (Dimocarpus longan) 屬於無患子科，龍眼屬植物，廣泛生長於臺灣、中國及東南亞等地區，在民間藥學上用以治療白帶、腎臟病等。本研究室先前研究指出龍眼花水萃物具有良好之體外抗 LDL 氧化活性，其主要活性成分為 (-)-epicatechin 及 proanthocyanidin A2 (PA2)。然而，目前 A-type 原花青素於生物體內生物可利用率之研究仍相當缺乏，故本研究之目的係以大鼠模式評估 PA2 之生物可利用率。以胃管餵食大鼠 200 mg/kg BW PA2 後，以斷尾採血方式收集血液，經 HPLC 分析後在血液中無法測得 PA2；以股靜脈注射給予大鼠 30 mg/kg BW PA2，測得 Cmax 為 24.60 ± 1.5 μg/mL，T1/2 為 8.46 ± 0.8 min；經計算後得 PA2 之口服生物可利用率為 0。當進行組織分佈探討時，各臟器中皆無法測得 PA2，其大多存在於腸胃道中，並隨著時間排出體外，胃管餵食後 8-12 hr 為 PA2 最大排除期，24小時後約 63% 自糞便排出體外。由體外腸道微生物發酵試驗結果可知 5-(3,4-dihydroxyphenyl)-γ-valerolactone 及3-hydroxyphenylpropionic acid (3-HPP) 為 PA2 之主要代謝產物，而在管餵大鼠 200mg/kg BW PA2 之腸道及尿液中亦可測得此代謝物。盲腸結紮試驗中測得 21 種腸道微生物代謝產物，其中以3-HPP、3,4-Dihydroxyphenylpropionic acid 及hippuric acid 為主。綜合以上試驗結果可知 PA2 在血液及組織中的濃度很低，但可藉由腸道微生物作用代謝成多種小分子的酚類化合物，此類代謝產物與 PA2 生理活性之相關性需進一步加以探討以了解 PA2 生理活性之作用機制。 | zh_TW |
| dc.description.abstract | Dimocarpus longan Lour., known as longan (dragon eye) in the Orient, belongs to the Sapindaceae family. Longan is a subtropical fruit widely grown in Taiwan, China and Southeast Asia. In traditional Chinese medicine the flowers are used for the treatment of leucorrhea and kidney disorders. The water extract of longan flower was found to possess high antioxidative activity against LDL oxidation in vitro. The major antioxidative compounds against LDL oxidation in longan flower were identified to be (-)-epicatechin and proanthocyanidin A2 (PA2). Intervention studies with procyanidin-rich extracts such as cocoa and wine suggest protective effects of proanthocyanidin against cardiovascular diseases. However, the bioavailiabily study of A-type proanthocyanidins is quite limited. The aim of this study was to evaluate the bioavailiabilty of PA2 following oral administration by Sprague-Dawley rats. After tube-feeding 250 mg/kg BW of PA2 for 2 hr, PA2 could not be detected in plasma. The pharmacokinetic parameter Cmax and T1/2 were 24.60±1.5 μg/mL and 8.46±0.8 min respectively after i.v. injection of 30 mg/kg BW PA2. The bioavailability of PA2 was almost 0. After tube-feeding 200 mg/kg BW of PA2 for 24 hr, 63% PA2 were excreted to feces. We used in vitro fermentation of PA2 with rat microbiota to examine the metabolites of PA2. The main metabolites of PA2 were 5-(3, 4-dihydroxyphenyl)-γ- valerolactone and 3-(3'-hydroxyphenyl) propionic acid (3-HPP). These metabolites of PA2 were also found in urine and intestine of rats tube-fed with 200 mg/kg BW PA2 indicating the possibility of absorption of PA2 after oral administration. After introducting PA2 (100 mg/kg BW) directly into the cecum for 6 hr, PA2 was found to be degraded into 21 phenolic acid compounds. The major metabolites were found to be 3-HPP, 3, 4-dihydroxyphenylpropionic acid and hippuric acid. Our results showed that intestinal microbiota could convert PA2 to a number of smaller phenolic compounds. The health potential of these metabolites should be further studied in order to understand the effect of PA2, since the PA2 concentrations in plasma and other tissues are very low. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T03:22:35Z (GMT). No. of bitstreams: 1 ntu-100-D95641004-1.pdf: 6016563 bytes, checksum: 3068f72b22f39ad6f0baa5f37846d196 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II 縮寫表 IV 目錄 VI 圖次 XI 表次 XV 附錄 XVI 壹、 前言 1 貳、 文獻整理 2 一、 龍眼花 2 (一) 龍眼簡介 2 (二) 龍眼花成分與功效 2 二、 原花青素及其生理活性 7 (一) 原花青素簡介 7 (二) 生理功效 9 三、 藥物動力學 15 (一) 吸收 (absorption) 17 1. 細胞膜的性質 17 2. 藥物在腸胃道的吸收 17 (二) 分佈 (distribution) 18 (三) 代謝 (metabolism) 18 四、 生物可利用率 24 (一) 生物可利用率定義 24 1. 絕對生物可利用率 24 2. 相對生物可利用率 24 (二) 原花性素的生物可利用率 24 (三) 酚類化合物之吸收、分佈及排除的研究 26 五、 酚類化合物於腸內菌群之代謝 31 (一) 腸道微生物對原花青素之代謝 31 (二) 腸道微生物對其他酚類物質之代謝 35 參、 研究目的與實驗架構 38 一、 研究目的 38 二、 實驗架構 39 (一) 大鼠藥物動力學試驗 40 (二) 大鼠體內分佈及排除試驗 41 (三) 模擬體內代謝試驗 42 肆、 材料與方法 44 一、 實驗材料 44 (一) 龍眼花 44 (二) Proanthocyanidin A2 44 二、 化學藥品與溶劑 44 三、 儀器設備 45 四、 實驗動物及動物飼料 47 五、 實驗方法 48 (一) Proanthocyanidin A2 之分離純化 48 1. 龍眼花 80% 丙酮萃取物之製備 48 2. 龍眼花 80% 丙酮萃取物之溶劑區分製備 48 3. Sephadex LH-20 管柱層析 50 4. MCI gel 管柱層析 51 5. 再結晶製備 proanthocyanidin A2 52 6. Proanthocyanidin A2 高效能液相層析 52 (二) Proanthocyanidin A2 藥物動力學參數測定 53 1. 動物飼養 53 2. Proanthocyanidin A2 血漿回收率測定 54 3. Proanthocyanidin A2 於血漿樣品之檢量線製作 54 4. 管灌餵食組 55 5. 靜脈注射組 55 6. Proanthocyanidin A2 於大白鼠的生物可利用率測定 56 7. 藥動參數分析 56 8. Proanthocyanidin A2 在血漿中之蛋白質結合率 57 (三) Proanthocyanidin A2 於大白鼠的吸收分佈及排除 57 1. 實驗動物飼養 57 2. 吸收與分佈試驗 58 3. 檢體萃取 58 4. 排除試驗 60 5. 高效液相層析分析條件 62 (四) Proanthocyanidin A2 之胃腸道模擬系統穩定性試驗 63 1. Proanthocyanidin A2 於模擬胃液中降解之研究 63 2. Proanthocyanidin A2 於模擬腸液中降解之研究 63 (五) Proanthocyanidin A2之腸內菌群代謝產物研究 63 1. Proanthocyanidin A2 與大鼠盲腸微生物共發酵試驗 63 2. 高效液相層析分析條件 64 (六) Proanthocyanidin A2 及其代謝產物之液相層析串聯質譜儀 (LC/MS/MS) 分析 64 伍、 結果與討論 71 一、 Proanthocyanidin A2 萃取與製備 71 (一) 龍眼花 80% 丙酮萃取物 (LF-A) 71 (二) 龍眼花 80% 丙酮萃取物之溶劑區分萃取 71 (三) 龍眼花丙酮粗萃物乙酸乙酯區分層 (LF-A-EA) 之 Sephadex LH-20 管柱層析 72 (五) 再結晶方式製得 proanthocyanidin A2 77 (六) 純化合物之結構分析與鑑定 77 二、 Proanthocyanidin A2藥物動力學參數 81 (一) Proanthocyanidin A2 分析方法之確效 81 (二) Proanthocyanidin A2 藥物動力學參數 83 1. 傳統採血法之 proanthocyanidin A2 回收率測定 83 2. 血漿中 proanthocyanidin A2 之藥物動力學及口服生物可利用率 86 3. Proanthocyanidin A2 在血漿中之蛋白結合率 87 三、 Proanthocyanidin A2 於大白鼠的吸收分佈及排除 91 (一) PA2 於大鼠體內之吸收與分佈試驗 91 (二) PA2 於大鼠尿液及糞便之排除情形 103 四、 以體外模擬試驗探討proanthocyanidin A2 可能之代謝途徑 108 (一) Proanthocyanidin A2 之胃腸道模擬系統穩定性試驗 108 (二) Proanthocyanidin A2 之大白鼠腸內菌群代謝產物研究 117 五、 Proanthocyanidin A2 於大白鼠各組織之代謝物分析 126 陸、 結論 151 柒、 參考文獻 152 捌、 附錄 163 | |
| dc.language.iso | zh-TW | |
| dc.subject | 代謝物 | zh_TW |
| dc.subject | 原花青素 A2 | zh_TW |
| dc.subject | 生物可利用率 | zh_TW |
| dc.subject | proanthocyanidin A2 | en |
| dc.subject | metabolites | en |
| dc.subject | bioavailability | en |
| dc.title | 以大鼠模式探討龍眼花 proanthocyanidin A2
的生物可利用性 | zh_TW |
| dc.title | Study on the Bioavailability of Proanthocyanidin A2
from Longan (Dimocarpus longan Lour.) Flower in Rat | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 徐鳳麟,蕭明熙,顏國欽,陳炳輝,何其儻,呂廷璋 | |
| dc.subject.keyword | 原花青素 A2,生物可利用率,代謝物, | zh_TW |
| dc.subject.keyword | proanthocyanidin A2,bioavailability,metabolites, | en |
| dc.relation.page | 172 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-07-29 | |
| 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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