Metabolism and Pharmacokinetics of 3,3′,4′,7-Tetrahydroxyflavone (Fisetin), 5-Hydroxyflavone, and 7-Hydroxyflavone and Antihemolysis Effects of Fisetin and Its Serum Metabolites
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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DOI：
10.1021/jf802378q
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发表时间：
2009-01-14
影响因子：
6.1
通讯作者：
Chao, Pei-Dawn Lee
中科院分区：
文献类型：
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作者：
Shia, Chi-Sheng;Tsai, Shang-Yuan;Chao, Pei-Dawn Lee
3，3 '，4'，7-四羟基黄酮（非瑟酮）具有多种生物活性。本文研究了非瑟酮、5-羟基黄酮和7-羟基黄酮在雄性SD大鼠体内的代谢和药代动力学。通过心脏穿刺抽取血液，并在用硫酸酯酶和β-葡萄糖醛酸酶水解之前和之后通过HPLC进行测定。结果表明，静脉注射非瑟酮（10 mg/kg体重）后，非瑟酮迅速下降，硫酸非瑟酮/葡萄糖醛酸苷瞬间出现。经口给予非瑟酮（50 mg/kg bw）时，非瑟酮母体仅在吸收阶段短暂存在于血清中，而非瑟酮硫酸盐/葡萄糖醛酸苷占主导地位。非瑟酮的血清代谢产物对2，2 '-偶氮二（2-脒基丙烷盐酸盐）（AAPH）诱导的溶血的抑制作用弱于非瑟酮。经口给予40 mg/kg bw的5-OH-黄酮和7-OH-黄酮后，在血清中发现5-OH-黄酮的葡糖苷酸和7-OH-黄酮的硫酸盐/葡糖苷酸，但未检测到痕量的母体形式。总之，非瑟酮和7-OH-黄酮被快速而广泛地生物转化为其硫酸盐/葡萄糖醛酸苷，而5-OH-黄酮则专门代谢为葡萄糖醛酸苷。
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-hydroxy-flavone (7-OH-flavone) in male Sprague-Dawley rats. Blood was withdrawn via cardiopuncture and assayed by HPLC before and after hydrolysis with sulfatase and beta-glucuronidase.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.