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

• Published in: Journal of agricultural and food chemistry 2009-01, Vol.57 (1), p.83-89
• Main Authors: Shia, Chi-Sheng, Tsai, Shang-Yuan, Kuo, Sheng-Chu, Hou, Yu-Chi, Chao, Pei-Dawn Lee
• Format: Article
• Language: English
• Subjects: 3,3',4',7-tetrahydroxyflavone; 5-hydroxyflavone; 7-hydroxyflavone; Animals; Bioactive Constituents; Biological and medical sciences; biotransformation; blood chemistry; blood serum; fisetin; fisetin glucuronides; fisetin sulfates; flavones; Flavonoids - blood; Flavonoids - metabolism; Flavonoids - pharmacokinetics; Flavonoids - pharmacology; Food industries; Fundamental and applied biological sciences. Psychology; Glucuronides - blood; hemolysis; Hemolysis - drug effects; Male; medicinal properties; metabolism; metabolites; oral administration; pharmacokinetics; protective effect; Rats; Rats, Sprague-Dawley; Sulfates - blood
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf802378q

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 Blood was withdrawn via cardiopuncture and assayed by HPLC before and after hydrolysis with sulfatase and β-glucuronidase.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.