Study on the Pharmacokinetics and Tissue Distribution of 5,7,3’,4’-tetramethoxyflavone in Rat

• Main Authors: Chia-Ling Tsai, 蔡佳玲
• Other Authors: Lucy Sun Hwang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/04206790385607193629

碩士 === 國立臺灣大學 === 食品科技研究所 === 101 === Polymethoxyflavones (PMFs), a special group of flavonoids with two or more methoxy groups on benzene ring (C6-C3-C6), have demonstrated many physiological activities similar to unmethylated flavones, but with higher bioavailability. 5,7,3’,4’-Tetramethoxyflavone (TMF) is one of the major polymethoxyflavones present in Kaempferia parviflora and Orthosiphon spicatus. Several studies have shown that TMF has many bioactivities such as anti-allergic activity, antifungal and anti-inflammatory effects, but the oral bioavailability of TMF is not clear so far. Thus, the purpose of this study is to investigate the bioavailability of TMF in Sprague-Dawley rats. In pharmacokinetic study, Cmax and T1/2 were determined to be 1.54±0.62 μg/mL and 62.85±27.92 minutes, respectively, after intravenous injection of 5 mg/kg BW of TMF. After tube feeding 50 mg/kg BW of TMF, the pharmacokinetic parameters of Cmax, Tmax and T1/2 were 0.79±0.30 μg/mL, 190±24.50 minute and 273±90.2 minutes, respectively. The bioavailability of TMF is 14.3%, much higher than some flavonoids. The lipophilicity methoxy of groups on TMF structure gave higher cell membrane permeability and improved metabolic stability, thus higher oral bioavailability was observed. In tissue distribution study, higher concentration of TMF were found in gastrointestinal tracts after tube feeding 50 mg/kg BW for 2 hour and 4 hours, stomach was shown to possess the highest content of TMF in 2 hours which contained up to 43% of dosing. TMF was also detected in brain. 3’-hydroxy-5,7,4’-trimethoxyflavone (M1), 4’-hydroxy-5,7,3’-trimethoxyflavone (M4) and 5-hydroxy-7,3’,4’-trimethoxyflavone (M5) were found to exhibit the tissue among the three metabolites of TMF, after feeding TMF. M1 plus M4 were also observed of 12 hours, after tube feeding 50 mg/kg BW TMF, M1 plus M4 reached the hightest concentration in all tissue containing up to 57 % of dosing. In excretion study, the main fecal excretion of TMF was found during 12-24 hours, containing about 0.8121 % of dosing, after tube feeding 50 mg/kg BW TMF. The main urinary excretion of TMF was found during 4-12 hours, TMF content in urine was only 0.0496% of dosing. The metabolites M1 plus M4 are the major metabolites in urine, the total amount of M1, M4 and M5 can reach 50 % of dosing. There are other possible urinary metabolites of TMF which should be further identified and quantified.