Preliminary Study On Pharmacokinetic Of Potentilla Flavone

The Chinese folk medicine Potentilla chinensis Bge(Rosaceae) is a perennial herb, and there are about 500 species worldwide,most of which distributed in northern temperate and boreal,only few are in the Southern Hemisphere.It is also called "Fan-bai-cai","Bai-tou-weng","Ha-ma-cao" and "Tian-qing-di-bai",listed in Chinese Pharmacopoeia 2000 and 2005.As a folk medicine,Potentilla chinensis has has been used to reduce swelling and staunch bleeding,and has anti-inflammatory and detoxification properties.In addition,P.chinensis revealed the therapeutic effect for controlling blood glucose and improving glucose tolerance of body in clinic.Our preliminary study showed that the main constituent of its hypoglycemic effect is kaempferol-3-O-β-D-(6-O-trans-p-coumaroyl)glucopyranside,which is named potentilla flavone(trans-tiliroside),and its hypoglycemic effect is better than phenformin hydrochloride.And its structure is different from biguanides, sulfonylureas,α-glycosidase inhibitors,thiazolidinedione,GLP-1R peptide agonist drug which indicates that there is a different anti-diabetic mechanism and is an active leading compound worth studying.In order to study potentilla flavone's medicinal value and pharmacophore,we do the preliminary pharmacokinetic's study on potentilla flavone to explore its structure-activity relationship and optimize its structure.During the first part,we studied the absorption of potentilla flavone in animal's intestinal tissue in vitro.Everted-gut technique was utilized to study the absorption properties of potentilla flavone at three different concentration range.The results show that the absorption of potentilla flavone increased by their concentration rising in a definite concentration range,as well as a concentration-depent.And the absorption of potentilla flavone fits to linear absorption model and the passive transport features.In addition,some potentilla flavone was hydrolysed into two hydrolysates.The two main contabolites of potentilla flavone in isolated rat small intestine were determined to be cinnamic acid and kaempferol-3-O-β-D-flavonoid glycoside. On basis of preliminary study on animal's intestinal tissue in vitro,we studied the blood concentration of potentilla flavone in vivo in second part of this paper.After tail vein injection to SD rats at three different concentration range,we determinate the concentration of potentilla flavone through HPLC and caculate the pharmacokinetic parameters.After intravenous injection of potentilla flavone at the dose of 10,20, 40mg/kg to rats,the average plasma-concentration datum were fitted to three-compartmental models(weight 1/c/c).The distribution half-life time(t_1/2α) and elimination half-life time(t_1/2β) of the three dose was 103.90 and 30580.98min,15.59 and 2045.70min,9.49 and 894.84min,respectively.All of these indicated the rapid distribution and a slow elimination.Besides,we do research on potentilla flavone's hydrolysates in vivo.Analysis potentilla flavone's structure and speculate its hydrolysate's possible structure,we compare the HPLC spectrums and make sure that there are three hydrolysatescinnamic, kaempferol and kaempferol-3-O-β-D-flavonoid glycoside.