(-)-Carvone Inhibits Oxytocin-induced Writhing Via Uterine Relaxation in Rodents.

ABSTRACT

(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.