Antinociceptive and antineuropathic effects of cuminaldehyde, the major constituent of Cuminum cyminum seeds: Possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: In Iranian traditional medicine, Cuminum cyminum is a unique medicinal herb for pain relief. Cuminaldehyde has been distinguished as the major constituent of C. cyminum seeds; even though, the analgesic effect of cuminaldehyde has not yet been examined. AIM OF THE STUDY: The nobility of this study was to assess cuminaldehyde effect on nociceptive and neuropathic pains; furthermore, evaluation of its possible mechanisms of action. MATERIALS AND METHODS: Hot plate, formalin, and acetic acid-induced writhing tests were used to evaluate nociception in mice. Naloxone (opioid receptors antagonist), L-arginine (nitric oxide (NO) precursor), L-NAME (NO synthase inhibitor), sodium nitroprusside (NO donor), methylene blue (guanylyl cyclase inhibitor), sildenafil (phosphodiesterase inhibitor), and glibenclamide (KATP channel blocker) were used to determine the implication of opioid receptors and L-arginine/NO/cGMP/KATP channel pathway. Allodynia and hyperalgesia were investigated in the CCI (chronic constriction injury) model of neuropathic pain in rats. The ELISA method was used to measure the inflammatory cytokines in serum samples of rats. The entire chemicals were intraperitoneally injected. RESULTS: Cuminaldehyde (100 and 200 mg/kg) significantly decreased the latency to nociceptive response in the hot plate test. The outcome of cuminaldehyde was completely antagonized by naloxone (2 mg/kg). Formalin- and acetic acid-induced nociception was significantly inhibited by cuminaldehyde (12.5-50 mg/kg). The antinociceptive effect of cuminaldehyde was reversed in writhing test by L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg); however, L-NAME (30 mg/kg) and methylene blue (20 mg/kg) enhanced the effect of cuminaldehyde. Glibenclamide (10 mg/kg) did not alter the antinociceptive effects of cuminaldehyde. In the CCI-induced neuropathy, cuminaldehyde (25-100 mg/kg) significantly alleviated allodynia and hyperalgesia and decreased the serum levels of TNF-α and IL-1ß. CONCLUSION: It was attained magnificently that cuminaldehyde exerts antinociceptive and antineuropathic effects through the involvement of opioid receptors, L-arginine/NO/cGMP pathway, and anti-inflammatory function.

Pharmacodynamic interaction of cumin seeds (Cuminum cyminum L.) with glyburide in diabetes.

Background and objective The plethora of anti-diabetic agents available today has many side effects, especially on chronic usage. Hence, alternative approaches utilizing natural and synthetic agents are sought after. Cumin has been shown to be beneficial in treating diabetes. This study evaluates the anti-diabetic effect of cumin and glyburide in the streptozotocin induced diabetes model in rats, and investigates their pharmacodynamic interactions and its implication in diabetes. Methodology The phytoconstituents present in the ethanolic cumin seed extract were determined using appropriate analytical methods. After acute toxicity studies (OECD 2001), the anti-diabetic effect of the extract was evaluated in wistar rats. The rats were divided into five groups - Groups I and II served as the normal and diabetic control. Group III was the standard control (glyburide 5 mg/kg), while groups IV and V received the extract (600 mg/kg) and a combination of the extract (600 mg/kg) and glyburide (2.5 mg/kg; half dose). Biochemical parameters viz. plasma glucose and glycosylated haemoglobin, were measured periodically during the 28 day treatment. On the 28th day, oral glucose tolerance test, lipid profile, renal profile and histopathological evaluation were performed after completion of the study. To investigate the nature of herb-drug interaction, HPLC analysis for estimation of glyburide concentration in the blood was conducted. Results Acute toxicity studies showed the extract to be safe till a dose of 2 g/kg. The extract alone, and in combination with glyburide (half-dose), significantly lowered elevated glucose (by more than 45% from baseline; without producing hypoglycemia), and other lipid and renal parameters. The effects produced by 2.5 mg/kg glyburide, and 5 mg/kg glyburide (without extract) were similar. Histopathological analysis also showed that the extract was able to reverse the degeneration brought about by streptozotocin which was especially notable on the pancreatic and renal tissue. HPLC analysis revealed differing pharmacokinetics of glyburide in the groups treated with 5 mg/kg dose, and 2.5 mg/kg + 600 mg/kg extract. Conclusion The results obtained in this study suggest that Cuminum cyminum L. is a promising anti-diabetic agent, and exhibits pharmacodynamic interaction with glyburide to mitigate symptoms of diabetes mellitus.

Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity.

Effect of feeding Cuminum cyminum fruits, Thymus vulgaris leaves or their mixture to rats.

Cuminum cyminum fruits and T. vulgaris leaves were fed to male Wistar rats at 2% or 10% of standard diet for 6 w. A mixture (5% +5%) of the 2 plants was also fed to rats for a similar period. Diets containing 2% C. cyminum fruits, 2% or 10% T. vulgaris leaves were not toxic to rats. Impairment of growth and enterohepatonephropathy were observed in the rats fed a diet containing 10% C. cyminum fruits. These changes were also seen in the rats fed the mixture of the 2 plants and were accompanied by leukopenia, anemia and increases in serum AST activity and urea and by decreased total protein and albumin levels.