Boswellic Acids Pretreatment Enhances the Bioavailability and Hypoglycemic Action of Metformin in Rats: Involvement of CYP3A Inhibition

Herbal antidiabetic preparations are often used as an add-on therapy in diabetes. Hence in the present investigation the effect of boswellic acids (BA) on the bioavailability and hypoglycemic action of metformin in normal as well as diabetic rats was studied. In normal and streptozotocin induced diabetic rats the combination of metformin with BA increased all the pharmacokinetic parameters such as Cmax, AUC0-n, AUCtotal, t½, MRT and decreased the clearance, Vd markedly as compared to control group. In intestinal and liver microsomes BA at 10μM has shown CYP3A4 inhibitory activity significantly (p<0.01), compared with the vehicle group. In pharmacodynamic studies,the combination of metformin with BA provided significant protection against the diabetes induced alterations in the biochemical parameters. In addition, the combination of metformin with BA also improved the total antioxidant status and decreased lipid peroxide levels significantly in diabetic rats compared with BA and metformin alone treated groups. The results revealed that BA led to the PK/PD changes have been due to metformin increased bioavailability, decreased volume of distribution and clearance byinhibiting the CYP3A enzyme. In conclusion, add-on preparations containing boswellia may increase the bioavailability and hypoglycemic action of metformin, and hence should be cautiously used.