Insulinotropic and β-cell protective action of cuminaldehyde, cuminol and an inhibitor isolated from Cuminum cyminum in streptozotocin-induced diabetic rats

Cuminum cyminum, a commonly used spice, is known to have anti-diabetic action. The present study aims towards the isolation of bioactive components from C. cyminum and the evaluation of their insulin secretagogue potential with the probable mechanism and beta-cell protective action. The anti-diabetic activity was detected in the petroleum ether (pet ether) fraction of the C. cyminum distillate and studied through in vivo and in vitro experiments. Bioactive components were identified through GC-MS, Fourier transform infrared spectroscopy and NMR analysis. The isolated components were evaluated for their insulin secretagogue action using rat pancreatic islets. Further, the probable mechanism of stimulation of islets was evaluated through in vitro studies using diazoxide, nifedipine and 3-isobutyl-1-methylxanthine. beta-Cell protection was evaluated using the (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan) (MTT) assay, the alkaline comet assay and nitrite production. The administration of the pet ether fraction for 45 d to streptozotocin-induced diabetic rats revealed an improved lipid profile. Cuminaldehyde and cuminol were identified as potent insulinotrophic components. Cuminaldehyde and cuminol (25 mu g/ml) showed 3.34- and 3.85-fold increased insulin secretion, respectively, than the 11.8 mM-glucose control. The insulinotrophic action of both components was glucose-dependent and due to the closure of the ATP-sensitive K (K+-ATP) channel and the increase in intracellular Ca2+ concentration. An inhibitor of insulin secretion with potent beta-cell protective action was also isolated from the same pet ether fraction. In conclusion, C. cyminum was able to lower blood glucose without causing hypoglycaemia or beta-cell burn out. Hence, the commonly used spice, C. cyminum, has the potential to be used as a novel insulinotrophic therapy for prolonged treatment of diabetes.