Study On α-glucosidase Activity And Pharmacokinetic Factors Of The Osmanthus Active Components In Vitro

This dissertation is composed of four chapters. Oleanolic acid and ursolic acid as activecompounds in Osmanthus active fraction were assayed in the former research. In order to study the factorsof α-glucosidase pharmacokinetics （PK）, the PK-PD model was established in vitro and the factors foroleanolic acid and ursolic acid pharmocodynetics （PD） were investigated.Chapter1: The eastabilishment and evaluation of PK-PD model ofα-glucosidase inhibitors in vitro.α-Glucosidase inhibitory activity oleanolic acid and ursolic acid was investigated and the halfinhibitory concentration （IC50） were4.73and4.84μg·mL^-1, respectively. PK-PD model was established bycombining the biological systems with the α-glucosidase inhibition method in vitro. Results showed thatα-glucosidase inhibitory activity of oleanolic acid and ursolic acid were lost completely after incubationwith rat liver microsomes at37°C for15min, but the inhibitoryactivity of acarbose after incubation withrat liver microsomes was similarto without incubation. The results showed that the metabolic or otherpharmacokinetic factors may affect the efficacy of oleanolic acid and ursolic acid in vitro, and it may bethe reason that the different effect of oleanolic acid and ursolic acid with acarbose in vivo.Chapter2: The metabolic stability evaluation: theactive compounds ofthe Osmanthus in rats liver microsomesThe metabolic stability of oleanolic acid and ursolic acid was evaluated using the method of thebiological systems and LC/MS/MS in rat liver micromoses in vitro. Results showed that NADPH andUDPGA were exist or not, the oleanolic acid had no enzyme degradation. In NADPH system, ursolic acid was metabolished about58.5%. Results showed that oleanolic acid had no relation with metabolism invitro, but the ursolic acid had a certain relation with metabolism, and the relation was not the main factorfor ursolic. It is necessary to investigate the pharmacokinetic factors of the drugs combined with proteins.Chapter3: Progress in the active compounds of CYP3A4, CYP2D6and CYP2C9as cytochrome P450enzymeProgress of the characteristics and active compounds of the enzyme cytochrome P450ofCYP3A4, CYP2D6were summarized.