Pharmacokinetics Of Phloretin And Phlorizin In Rats From Apple Polyphenol Extract

Apple polyphenols are secondary metabolites produced by apples with multiple hydroxyl groups in the general structures. The major components of this group include the procyanidins B2, phloridzin, phloretin, catechin, epicatechin, chlorogenic acid and other compounds. Many studies show that apple polyphenols have anti-radiation, anti-oxidation, anti-tumor, anti-caries, anti-allergy, anti-microbial, regulate lipid metabolism, and other biological activities. Their anti-oxidative effect is fifty time potent than vitamine E, and twenty times potent than vitamine C, and therefore have broad application prospects in either food or health care products field.Destination:To provide the experimential data for the new drug development of apple polyphenols, and illustrate the metabolism process in vivo, and adopt a high performance liquid chromatography -mass spectrum method to study pharmacokinetics of phloretin and phlorizin in rats from apple polyphenol extract.Methods:We chose 168 healthy male Wistar rats, randomly divided into high, medium and low dose group (administration dose are 2.0,1.0,0.5 g/kg, respectively), blood was taken in a total of 14 time points respectively 0 h to 12 h after administration. After blood samples were pretreatmented by centrifugation and protein deposition, HPLC-MS was used to detect the content of phloretin and phloridzin in plasma samples, then rendering concentration-time curve of phloretin and phloridzin and calculating pharmacokinetics parameters of them. The chromatographic conditions was showed as follows:the column was Diamonsil C18 (5μm,250×4.6 mm); the mobile phase was methanol-0.1% ammonia water (40:60, V/V); the flow rate was 0.8 mL·min-1; the column temperature was 25℃; the ion was detected by selective ion monitor (SIM) in a negative mode; The selected ions were m/z 273.0 for phloretin, m/z 435.1 for phloridzin, and m/z 327.2 for the internal standard bergenin. The data observed was processed using DAS soft ware, and then calculated the concentration-time cure and pharmacokinetic parameters of phloretin and phloridzin.Results:For phloretin, half-life T1/2 in high, medium and low dose group were 1.108 h,1.715 h, and 0.747 h; peak time of Tmax were 1.875 h,1.875 h, and 2.0 h; peak plasma levels were 257.77μg/L,61.639μg/L, and 22.965μg/L; the area under the curve (AUC) were 784.374μg/L*h,190.107μg/L*h, and 63.62μg/L*h; The mean residence time (MRT) were 2.563 h,2.995 h, and 2.276 h. For phloridzin, half-life T1/2 of in high, medium and low dose groups were 1.463 h,1.382 h, and 1.209 h; peak time of Tmax were 1.0 h,0.688 h, and 0.625 h; peak plasma levels were 1526.056μg/L, 294.354μg/L, and 77.946μg/L; the area under the curve (AUC) were 2004.451μg/L*h,452.166μg/L*h, and 79.639μg/L*h; the mean residence time (MRT) were 1.535 h,1.503 h, and 1.435 h.Conclusion:The absorption process of phloretin and phloridzin were very quickly, and the analytes were able to be detected in five after drug administration. The Tmax of phloretin was about 2 h, and less than 1 h for phloridzin. Both phloretin and phloridzin was able to be nearly completed eliminated in rats within 12 h. The results from this study show that the metabolism process of phloridzin and phloretin in rats were fitted to the two-compartment model. The result will provide useful information for the new drug development of apple polyphenols in the future.