以大鼠模式探討芝麻 Lignan 化合物的生物可利用性

Abstract

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.