Metabolism and Pharmacokinetics of 3,3′,4′,7-Tetrahydroxyflavone (Fisetin), 5-Hydroxyflavone, and 7-Hydroxyflavone and Antihemolysis Effects of Fisetin and Its Serum Metabolites

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• 作者：Chi-Sheng Shia ; Shang-Yuan Tsai ; Sheng-Chu Kuo ; Yu-Chi Hou ; Pei-Dawn Lee Chao
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2009
• 出版时间：January 14, 2009
• 年：2009
• 卷：57
• 期：1
• 页码：83-89
• 全文大小：215K
• 年卷期：v.57,no.1(January 14, 2009)
• ISSN：1520-5118

文摘

3,3′,4′,7-Tetrahydroxyflavone (fisetin) has shown various beneficial bioactivities. This study investigated the metabolism and pharmacokinetics of fisetin, 5-hydroxyflavone (5-OH-flavone), and 7-hydroxyflavone (7-OH-flavone) in male Sprague−Dawley rats. Blood was withdrawn via cardiopuncture and assayed by HPLC before and after hydrolysis with sulfatase and β-glucuronidase. The results indicated that after intravenous administration of fisetin (10 mg/kg of bw), fisetin declined rapidly and fisetin sulfates/glucuronides emerged instantaneously. When fisetin (50 mg/kg of bw) was given orally, fisetin parent form was transiently present in serum only during the absorption phase, whereas fisetin sulfates/glucuronides predominated. The serum metabolites of fisetin showed less potent inhibition on 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced hemolysis than fisetin. Following oral administrations of 40 mg/kg of bw of 5-OH-flavone and 7-OH-flavone, the glucuronide of 5-OH-flavone and the sulfate/glucuronide of 7-OH-flavone were found in serum, whereas no traces of parent forms were detected. In conclusion, fisetin and 7-OH-flavone were rapidly and extensively biotransformed into their sulfate/glucuronide, whereas 5-OH-flavone was exclusively metabolized to glucuronide.