ABSTRACT
Type 2 diabetes (T2DM) is a progressive insulin secretory defect accompanied by resistance to insulin, and thereby making glycemic control a major concern in the treatment of these patients. Oral drug administration, though a popular option for its non-invasiveness, suffer from poor bioavailability. It could be related to the efflux transport of intestinal P-glycoprotein (Pgp). In the present study, we explored the binding interactions of antidiabetic drugs i.e., sulfonylurea drugs (glimepiride, glipizide, glyburide) and rapid acting insulin secretagogues viz., nateglinide, repaglinide and rosiglitazone; and Pgp inhibitors i.e., Generation I (verapamil and tamoxifen), III (tetradrine and tariquidar), and natural inhibitors (fumagillin and piperine) in mouse Pgp model. Our results revealed that fumagillin piperine and verapamil possess maximum interaction energies with Pgp compared to antidiabetic drugs. These observations elucidate the role of fumagillin and piperine as potential natural compounds which could intervene in the efflux action of Pgp in extruding the antidiabetic drugs and may have implications for increasing efficacy of oral antidiabetic therapy.
ABSTRACT
The cerebral ischemia was produced by Pulsinellis method in Sparaque-Dawley rats. The brain edema and survival rate of rats with bilateral carotid and vertebral arteries occlusion for 60 min were observed in ip tetradrine at doses of 1 ~ 4 mg/kg groups and control rats.Superoxide dismutase and malondialdehyde in brain tissue were also measured by pyrogallol method and fluorescence spec-trometry. The results suggested that tetradrine have protective effect on cerebral ischemia, which was related to the inhibition of lipoxide and scavenging of oxygen free radical.