Curcumin pharmacokinetic and pharmacodynamic evidences in streptozotocin-diabetic rats support the antidiabetic activity to be via metabolite(s)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

This study measures the curcumin concentration in rat plasma by liquid chromatography and investigates the changes in the glucose tolerance and insulin sensitivity of streptozotocin-diabetic rats treated with curcumin-enriched yoghurt. The analytical method for curcumin detection was linear from 10 to 500 ng/mL. The C-max and the time to reach C-max (t(max)) of curcumin in plasma were 3.14 perpendicular to 0.9 mu g/mL and 5 minutes (10 mg/kg, i.v.) and 0.06 perpendicular to 0.01 mu g/mL and 14 minutes (500 mg/kg, p.o.). The elimination half-time was 8.64 +/- 2.31 (i.v.) and 32.70 +/- 12.92 (p.o.) minutes. The oral bioavailability was about 0.47%. Changes in the glucose tolerance and insulin sensitivity were investigated in four groups: normal and diabetic rats treated with yoghurt (NYOG and DYOG, resp.) and treated with 90 mg/kg/day curcumin incorporated in yoghurt (NC90 and DC90, resp.). After 15 days of treatment, the glucose tolerance and the insulin sensitivity were significantly improved in DC90 rats in comparison with DYOG, which can be associated with an increase in the AKT phosphorylation levels and GLUT4 translocation in skeletal muscles. These findings can explain, at least in part, the benefits of curcumin-enriched yoghurt to diabetes and substantiate evidences for the curcumin metabolite(s) as being responsible for the antidiabetic activity.