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

Abstract

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 β-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. β-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 μg/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 β-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 β-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.

Ethnopharmacological knowledge of Shiraz and Fasa in Fars region of Iran for diabetes mellitus

“…Cuminaldehyde and cuminol, secondary metabolites from C. cyminum L. showed 3.34-and 3.85-fold increase in insulin secretion, respectively, in diabetic rat model (Patil et al, 2013).…”

Cuminaldehyde: A Potential Drug Candidate

“…Later, Patil et al [20] 2013 showed that cuminaldehyde had glucose dependent insulinotropic effects in diabetic rats, an effect which was found to be mediated through blocking ATP sensitive potassium channels and increasing intracellular calcium concentration in cultured rat pancreatic cells. Moreover, cuminaldehyde protected pancreatic β cells against cytotoxicity induced by streptozotocin [20].…”

Evaluation the effect of 50 and 100 mg doses of Cuminum cyminum essential oil on glycemic indices, insulin resistance and serum inflammatory factors on patients with diabetes type II: A double-blind randomized placebo-controlled clinical trial

“…But in another study performed on overweight subjects, no meaningful effect of C. cyminum on plasma glucose in a fasting state and lipid profile was detected 24 . As most studies have been performed on laboratory animals,16, 25, 26, 27, 28, 29, 30 and due to lack of comparison on the rate of effectiveness of the different doses of this plant on patients with diabetes type II as well as controversial outcomes of the studies, it is essential to compare the effectiveness of the different doses of green cumin extract. Therefore, the present study was designed for the purpose of evaluating the effect of 50 and 100 mg doses of essential oil of C. cyminum on the glycemic indices and some inflammatory indices (TNF-α, adiponectin and hsCRP) in patients with diabetes type II.…”

“…This plant has antioxidant properties and it has been used in traditional medicine as a stimulant, carminative, and coagulant 15 . Studies on laboratory animals have shown that essential oil of C. cyminum has anti-diabetic properties 16 . The effective components of this plant are Cumin aldehyde, γ-Terpinine, α-Sabinin, α-Flandren and α-Kadinin, 17 of which Cuminaldehyde or 4-Isopropil Benzaldhyde is the most effective.…”