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研究生:詹國靖
研究生(外文):Kuo-Ching Jan
論文名稱:以大鼠模式探討芝麻Lignan化合物的生物可利用性
論文名稱(外文):Study on the Bioavailability of Lignan Compounds fromSesame in Rat
指導教授:孫璐西孫璐西引用關係
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:食品科技研究所
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:219
中文關鍵詞:芝麻sesamolsesaminol trigluosidesesaminol生物可利用率
外文關鍵詞:sesamesesamolsesaminol trigluosidesesaminolbioavailability
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芝麻具有很多有益的生理功效,主要與它的lignan化合物有關,例如sesamol、sesaminol triglucoside及sesaminol。Sesamol (benzo[1,3]dioxol-5-ol, MW 138)已被證實為芝麻油中主要抗氧化物質,sesaminol triglucoside 在體內試驗並無抗氧化效果,但是有文獻指出,在大鼠體內可轉變成酚類化合物,在體內具有抗氧化活性。本研究在Sprague Dawley大鼠體內探討sesamol、sesaminol triglucoside及sesaminol之生物可利用性,sesamol、sesaminol triglucoside及sesaminol以管餵及靜脈注射方式,測其藥物動力學參數。以管餵及靜脈注射給予sesamol、sesaminol triglucoside及sesaminol後,經靜脈採血方式收集血液,藥物動力學參數係以非室模式計算所得,結果顯示sesamol、sesaminol triglucoside及sesaminol口服生物可利用率分別為35.5 ± 8.5、0.31 ± 0.04及21.1 ± 3.47 %。我們並以管餵sesamol (100 mg/kg p.o.) 予SD大鼠,測定其組織分佈,於管餵24小時後測定各組織及血漿sesamol濃度變化,發現sesamol可以通過血腦障壁,並且經由腸肝循環排除。Sesamol代謝物(glucuronide) 廣泛分佈於老鼠組織中,在肝臟及腎臟有最高濃度,而腦部濃度為最低。在SD大鼠體內sesaminol triglucoside及sesaminol之生物可利用探討,乃以管餵sesaminol triglucoside及sesaminol (500 mg/kg, 220 mg/kg p.o.) 24小時後測定各組織及血漿sesamol濃度變化,結果顯示,sesaminol triglucoside經由腸內菌水解去除醣基後形成sesaminol,經由淋巴被吸收進入心血管系統,並運送至其他組織 (肺臟、肝臟及腎臟)。Sesaminol triglucoside及sesaminol代謝物 (sesaminol sulfate/glucuronide) 被發現存在於大鼠許多組織中,在心臟、肝臟及腎臟有較高濃度,而腦部濃度為最低。Sesaminol triglucoside及sesaminol代謝物 (sesaminol sulfate/glucuronide)排除很快,以LC/MS/MS分析其代謝物,發現sesaminol triglucoside及sesaminol可受到大鼠體內腸內菌之作用而轉變成mammalian lignan (enterolactone)。
Sesame exhibits many beneficial physiological effects, which are mostly related to its lignan compounds, such as sesamol, sesaminol glucosides and sesaminol. Sesamol (benzo[1,3]dioxol-5-ol, MW 138) has been generally regarded as the main antioxidative component in sesame oil. Sesaminol glucosides have no antioxidative properties in vitro, but they have been reported to be converted to phenolic compounds after oral administration to rat and showed antioxidative activity in vivo. This investigation intends to study the bioavailability of sesamol, sesaminol glucosides and sesaminol in Sprague Dawley rats. Sesamol, sesaminol glucosides and sesaminol were introduced to rats via gastric gavage (p.o.) or intravenous injection and the various pharmacokinetic parameters were determined. Biological fluid was intravenously sampled following a dose of sesamol, sesaminol glucosides and sesaminol via gastric gavage or by intravenous injection. The pharmacokinetic data of sesamol, sesaminol glucosides and sesaminol were calculated by non-compartmental model. Our results showed that the oral bioavailability of sesamol, sesaminol triglucoside and sesaminol were 35.5 ± 8.5, 0.31 ± 0.04 and 21.1 ± 3.47%, respectively. We have also investigated the distribution of sesamol (100 mg/kg p.o.) in SD rats, the concentration changes of sesamol were determined in various tissues and plasma within 24 h period after oral administration to SD rats. In addition, sesamol was found to be able to penetrate the blood-brain barrier and go through hepatobiliary excretion. Sesamol metabolites (glucuronide) was widely distributed in SD rat tissues, with the highest concentrations in liver and kidneys and the lowest in brain. The bioavailabilities of sesaminol triglucoside and sesaminol were studied in Sprague Dawley rats. In order to investigate the distribution of sesaminol triglucoside and sesaminol (500 mg/kg, 220 mg/kg p.o.) in SD rats, the concentration changes of sesaminol triglucoside and its metabolites were determined in tissues and plasma within 24 h period after tube-feeding to SD rats. Results showed that sesaminol triglucoside may be deglycosylated to from sesaminol first by intestinal microflora and then incorporated via lymphatic absorption into the cardiovascular system, transported to other tissues (lung, liver, and kidneys). Metabolites of sesaminol triglucoside and sesaminol (sesaminol sulfate/glucuronide) were found in many tissues of rat, they were present in higher concentrations in heart, liver and kidneys while the lowest in brain. The eliminations of the metabolites of sesaminol triglucoside and sesaminol (sesaminol sulfate/glucuronide) were fast. From LC/MS/MS analysis of rat excreta, sesaminol triglucoside and sesaminol can be converted to mammalian lignan (enterolactone) in vivo by rat intestinal microflora.
目 錄
頁次
口試委員會審定書 I
中文摘要 II
英文摘要 II
目錄 IV
表次 VIII
圖次 XI
壹、前言 1
貳、文獻回顧 2
一、芝麻簡介 2
二、芝麻中lignan化合物的簡介 2
三、芝麻之生理機能 6
四、生物可利用率 10
(一) 外來物(xenobiotics)在生物體內之吸收及代謝 10
(二) 酚類化合物之生物可利用率 20
(三) Lignan化合物之吸收代謝與生物可利用率 25
(四) Lignan化合物之生物體代謝 28
参、研究目的與實驗設計 35
ㄧ、研究目的 35
二、實驗設計 36
肆、實驗材料與方法 38
一、實驗材料 38
二、化學藥品與溶劑 38
三、動物飼料 40
四、儀器設備 40
五、實驗方法 43
伍、結果與討論 60
一、Sesaminol triglucoside (ST)及sesaminol萃取與製備 60
二、Sesamol、sesaminol及sesaminol triglucoside (ST)藥物動力學參數 62
(一) Sesamol、sesaminol及ST分析方法之確效 62
(二) Sesamol之藥物動力學參數 63
(三) Sesaminol、ST之藥物動力學參數 64
三、Sesamol、sesaminol及sesaminol triglucoside (ST)於大白鼠的吸收分佈
及排除 69
(一) Sesamol、sesaminol及ST於大鼠體內之組織分佈 71
四、Sesamol、sesaminol及sesaminol triglucoside (ST)之糞便及尿液排除 76
(一) Sesamol、sesaminol及sesaminol triglucoside (ST)之尿液排除 77
(二) Sesamol、sesaminol及sesaminol triglucoside (ST)之糞便排除 78
五、Sesamol、sesaminol triglucoside (ST)及sesaminol於大白鼠的代謝途徑 80
(一) Sesamol、sesaminol triglucoside (ST)及sesaminol之胃腸道模擬系統
穩定試驗及大鼠腸道微生物培養試驗 80
(二) Sesamol、sesaminol triglucoside (ST)及sesaminol於大鼠體內代謝物分析 81
(三) Sesaminol及ST於大鼠體內之enterodiol代謝途徑探討 87
(四) Sesamol、sesaminol triglucoside及sesaminol於大鼠體內代謝途徑之探討 88
陸、結論 93
柒、參考文獻 95
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