The Absorption And Metabolism Research Of Calycosin Of Active Ingredient In Astragalus

Astragalus is the root of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao or Astragalus membranaceus(Fisch.)Bge.which shows the effects of qi Sun,solid form antiperspirant,water swelling,fluid and blood.For the treatment of peptic ulcer,diabetes and its complications,cancer,lung disease,chronic gastritis and other diseases clinic.Astragalus contains many ingredients flavonoids,saponins,polysaccharides,amino acids,etc.In recent years,Astragalus flavonoids become a hot topic at home and abroad,calycosin is the main active substance of its flavonoids,with a variety of pharmacological activities,such as anti-malarial parasite,protect vascular endothelial cells,anti-hypertensive,anti-hyperglycemia,neuroprotection,skin whitening agents,enhance hematopoietic function,estrogen therapy,and leukemia.However,in vivo studies of the process is not much Calycosin,so research calycosin has some significance in the absorption and metabolic characteristics of the body.The experiments established the measurement of ultra-high phase liquid chromatography-mass spectrometry(UPLC-MS-MS),high performance liquid(HPLC)analysis method of Calycosin,this method is sensitive,fast,simple,specific,and can be used quantitative analysis calycosinThis subject studys the pharmacokinetic parameters of Calycosin was initially investigated by in vivo pharmacokinetic model of rats.The parameters from oral aministration study are Tmax 1.25±0.387h,AUC(0??)594.364±66.303ng·L-1·h-1?MRT(0-t)3.764±0.119?CL 33988.756±3673.103L·h-1·kg-1.The parameters from intravenous administration study are AUC(0-?)? 226.034±16.934ng·L-1·h-1?MRT0?h0.77±0.086?CL4445.739±347.303L·h-1·kg-1.Through the comparison of calycosin intravenous and oral AUC,the bioavailability of Calycosin after oral administration is 13.15%.Secondly,the absorption characteristics of calycosin has use one-way intestinal perfusion model of rat,analyzes different doses and in different intestinal segments(duodenum,jejunum,ileum,colon)absorption characteristics.The results show that calycosin has good stability in K-R solution of pH 6.03?8.02,different concentrations of calycosin values were significantly different in the different segments of intestine in rats Peff and Ka,in rat small intestine inhibited its concentration.The absorption of Calycosin maybe active transport into the systemic circulation,and in the duodenum,jejunum,ileum absorption is better than that of colon.Then,the absorption characteristics of calycosin has use the Caco-2 cell monolayer,to assist the study of the absorption characteristics calycosin,were studied at different concentrations and absorption transport characteristics of respectively adding different types of protein inhibitors.The results show that low,middle,high concentration of Papp(BL-AP)/Papp(AP-BL)=1.38<1.5,respectively adding different types of protein inhibitors,compared with the control group of Papp(BL-AP)/Papp(AP-BL),there were no significant differences.Calycosin absorption may mainly passive transport,also involved in active transport mechanism,the transport may not be affected by the P-protein,MRP2 protein,SGLT protein.Finally,the model of rat liver microsomal metabolic properties calycosin respectively studied its phase ? and phase ? metabolic characteristics in rat liver;for larger amounts of phase ? metabolic,and further study is what Calycosin metabolic enzyme substrates.The results showed that calycosin vivo in rat liver microsomes was incubated at 37 ? for 60min,was the apparent first-linear elimination,and in the inactivation of rat liver microsomal metabolism is not.Calycosin is described by the rat liver microsomal metabolism calycosin in rat liver microsomes I phase metabolic rate 9.41%,? phase metabolic rate was 20.58%-compared to indicate calycosin higher metabolism in the liver in phase ?.For phase ? after metabolism,further studies with different metabolic enzyme substrate specificity,metabolism compared with the control group,the results showed that after adding estradiol and naproxen,reduce the amount of metabolites were significantly different(P<0.05),suggesting a role may calycosin in liver microsomes in phase ? metabolic reaction process by UGT1A1,UTG1A3,UGT1A6?UGTlA9and UGT2B7,is the common substrate UGT1A1?UTG1A3?UGT1A6?UGT1A9and UGT2B7.