Metabolism and pharmacokinetics of 3,3',4',7-tetrahydroxyflavone (fisetin), 5-hydroxyflavone, and 7-hydroxyflavone and antihemolysis effects of fisetin and its serum metabolites.
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 Blood was withdrawn via cardiopuncture and assayed by HPLC before and after hydrolysis with sulfatase and beta-glucuronidase.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.
Shia
Chi-Sheng
CS
Institute of Pharmaceutical Chemistry and School of Pharmacy, China Medical University, Taichung, Taiwan.
Tsai
Shang-Yuan
SY
Kuo
Sheng-Chu
SC
Hou
Yu-Chi
YC
Chao
Pei-Dawn Lee
PD
D000818:Animals; D005419:Flavonoids / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D044948:Flavonols; D020719:Glucuronides / Q000097:blood; D006461:Hemolysis / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000097:blood
D005419:Flavonoids; D044948:Flavonols; D020719:Glucuronides; D013431:Sulfates; C062711:5-hydroxyflavone; C017875:fisetin; C429845:7-hydroxyflavone