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  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 生化科技學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52601
標題: 紅麴聚酮二次代謝產物 monascin 與 ankaflavin 之藥物動力學研究
Study on the pharmacokinetics of Monascus secondary polyketide metabolites, monascin and ankaflavin
作者: Ji-Syun Sun
孫基訓
指導教授: 潘子明(Tzu-Ming Pan)
關鍵字: 紅麴,monascin,ankaflavin,藥物動力學,
Monascus,monascin,ankaflavin,pharmacokinetics,
出版年 : 2015
學位: 碩士
摘要: 紅麴色素為紅麴次級代謝物之一,近年來有文獻指出紅麴之黃色素 monascin 與 ankaflavin 具有良好的生理活性功能,例如免疫抑制的效果,而 monascin 亦被證實具有抗發炎以及抑制皮膚癌的作用;ankaflavin 則可誘發癌細胞走向細胞凋亡而具有抗癌的效果,為極具保健功效潛力的天然化合物。Monascin 與 ankaflavin 具多種生理功效,然而目前對於 monascin 與 ankaflavin 在動物模式之藥物動力學研究仍然缺乏,故本研究乃探討 monascin 與 ankaflavin 於大鼠模式下的藥物動力學、組織分佈與排除情形,來瞭解兩物質之藥物動力學參數及生物可利用率、尋找與確認其標靶器官、尋找新的作用途徑以及體內的積蓄情形。本研究藥物動力學試驗的結果顯示,以管餵方式給予大鼠 150 mg/kg BW monascin 或 ankaflavin 後,以極致效能液相層析串聯質譜儀 (ultra performance liquid chromatography-tandem mass spectrometer, UPLC-MS/MS) 在血漿測得之血漿最高濃度 Cmax 分別為 0.62 ± 0.08 μg/mL 及 0.95 ± 0.28 μg/mL,半衰期分別為 230.64 ± 104.54 min 及 184.13 ± 57.99 min。以股靜脈注射給予大鼠 15 mg/kg BW 之 monascin 或 ankaflavin 後,在血漿測得之 Cmax 分別為 4.25 ± 3.91 μg/mL 及 4.55 ± 4.23 min,半衰期分別為 123.44 ± 40.96 min 及 78.91 ± 42.54 min。經公式計算後得 monascin 與 ankaflavin 之口服生物可利用率分別為 15.67% 與 20.36%。組織分佈試驗結果顯示,monascin 與 ankaflavin 皆可分佈至大腦、心臟、肺臟、肝臟、腎臟、胰臟、胃、腸道及脂肪。在腦中可發現 monascin 與 ankaflavin 的存在,推測兩化合物皆可通過血腦障壁。管餵後 0.5 小時在腸胃道即含有大量的 monascin 與 ankaflavin,尤其以胃中含量最高。排除試驗結果顯示,糞便為 monascin 與 ankaflavin 的主要排除途徑。管餵後 12-16 小時為 monascin 及 ankaflavin 於糞便中之主要排除期。管餵後 48 小時內,分別有給予劑量的 24.70% 及 1.10% 以原型態型式經由糞便排出體外。藉由本研究瞭解 monascin 與 ankaflavin 於大鼠模式下之藥物動力學參數、口服生物可利用率、組織臟器分佈與排除情形,可提供未來臨床應用的參考。
Recently, the research of Monascus-fermented secondary metabolites, monascin and ankaflavin, was gradually popular. The functions of monascin and ankaflavin include anti-inflammation, cancer prevention, hypolipidemic effect, blood glucose regulation and reducing the steatosis effect. There are many bioactivities of monascin and ankaflavin, however, the information on pharmacokinetics, distribution and excretion of monascin and ankaflavin is still absent. The aim of this study was to investigate the pharmacokinetics, distribution and excretion characteristics of monascin and ankaflavin in Sprague-Dawley rats after intravenous or oral administration. After the UPLC-MS/MS analysis, the pharmacokinetic study showed that after oral administration of 150 mg/kg BW of monascin or ankaflavin, the pharmacokinetic parameter Cmax of monascin and ankaflavin were 0.62 ± 0.08 μg/mL and 0.95 ± 0.28 μg/mL, respectively. T1/2 were 230.64 ± 104.54 min and 184.13 ± 57.99 min respectively. After intravenous injection of 15 mg/kg BW of monascin or ankaflavin, results showed that Cmax were 4.25 ± 3.91 μg/mL and 4.55 ± 4.23 min, T1/2 were 123.44 ± 40.96 min and 78.91 ± 42.54 min, respectively. The bioavailability of monascin and ankaflavin were 15.67% and 20.36%, respectively. The distribution study showed that monascin and ankaflavin were distributed widely in various tissues. After oral administration of monascin or ankaflavin in a dose of 150 mg/kg, they could be found in brain, heart, liver, lung, kidney, pancreas, stomach, intestine and fat. Higher concentrations of monascin and ankaflavin were found in the gastrointestinal tract after oral administration for half hours. The excretion study showed that after oral administration of monascin or ankaflavin, the fecal excretion was found to be the major excretion route of these two compounds. The major excretion period of monascin and ankaflavin occurred in 12-16 hours after oral administration. Furthermore, 24.70% of the oral administered monascin was excreted as unconverted form in fecal excretion and ankaflavin was 1.10%. This study improved the understanding of the tissue distribution and excretion of monascin and ankaflavin in rats and may provide a meaningful basis for clinical application of these bioactive compounds.
URI: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52601
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