Study On Effect Of Radix Astragali On Main Active Ingredient Of Radix Saposhnikoviae In Rats In Vivo

RS and RA, as a classical and effective herb couple, are used frequently in clinical medicine. Modern research shows that chromone, such as prim-O-glucosylcimifugin, 5-O-methylvisamminol and cimifugin of RS, is the main material basis for therapeutic effects. When RS and RA are used of compatibility, they have anti-oxidation and immune-enhancing activities.This topic is mainly carried out to study on effect of RA on main active ingredients of RS in rats in vivo by pharmacokinetics, absorption and metabolism.It was initially investigated that the bioavailability of prim-O-glucosylcimifugin,5-0-methylvisamminol and cimifugin of RS and the effect of RA on bioavailability of them by the rat in vivo kinetic models in the studies. The concentration of prim-O-glucosylcimifugin,5-O-methylvisammioside and cimifugin in the plasma were determinated after oral administration of RS and RS-RA aqueous extract to rats. The date was processed by using DAS 3.2.4. Comparing with RS group, the pharmacokinetic parameters Tmax, Cmax, AUCo-t and AUC0-∞ of prim-O-glucosylcimifugin were significantly increased and CL was significantly lowed in RS-RA group; Tmax of 5-O-methylvisammioside was significantly increased and Cmax, AUCo-t and AUC0-∞ of 5-O-methylvisammioside had a tendency of increase in RS-RA group; Tmax, AUC0-t, AUC0-∞ of cimifugin were significantly increased but Cmax of cimifugin was significantly lowed in RS-RA group. The results indicated RA could increase the bioavailability of three chromones of RS.To study the influence of RA extract on the absorption of prim-O-glucosylcimifugin, 5-O-methylvisamminol and cimifugin of RS, the rat in situ intestinal perfusion model and Caco-2 cell model were used as platforms. The results showed that RA extract had no significant influence on the absorption of prim-O-glucosylcimifugin,5-O-methylvisamminol and cimifugin of RS.The influence of RA extract on the metabolic process of prim-O-glucosylcimifugin, 5-O-methylvisamminol and cimifugin of RS extract in the rat intestinal microflora and liver microsomes were investigated. The intestinal microflora experiment about the concentration comparison of prim-O-glucosylcimifugin,5-O-methylvisammioside and cimifugin between RS group and RS-RA group were carried out at different time points. Then the concentration comparison of monomer between monomer group and monomer-RA group were carried out at different time points. The results showed that, compared to RS group, the concentration of prim-O-glucosylcimifugin and 5-0-methylvisammioside were higher, however, the concentration of cimifugin was lower in RS-RA group. Compared to monomer group, the concentration of prim-O-glucosylcimifugin and 5-O-methylvisammioside were higher and the concentration of cimifugin was lower in monomer-RA group. It indicated that RA could inhibit the biotransformation of prim-O-glucosylcimifugin and 5-O-methylvisammioside and slow down the metabolism.The liver microsomes experiment about the residue comparison of prim-O-glucosylcimifugin,5-O-methylvisammioside and cimifugin between RS group and RS-RA group were carried out, then liver microsomes experiment about the residue comparison of cimifugin between cimifugin group and cimifugin-RA group were carried out. It was found that the residue of cimifugin in RS-RA group was greatly increased compared with that in RS group in SD rat liver microsomes after the II phase metabolism by the incubation system of liver microsomes, and the residue of cimifugin in cimifugin-RA group was greatly increased compared with that in cimifugin group, which indicated that the metabolism of cimifugin in RS may be influenced by RA in Phase II.In this study, the rationale of the combined use of RS and RA was investigated from the perspective of pharmacology and biopharmaceutics by various models. The effect of RA on prim-O-glucosylcimifugin,5-O-methylvisamminol and cimifugin of RS in rats in vivo by pharmacokinetics, absorption and metabolism, which clarified preliminarily the rationale of the combined use of RS and RA from the perspective of biological pharmacy.