Role of Ascaridole and p-Cymene in the Sleep-Promoting Effects of Dysphania ambrosioides Essential Oil via the GABAergic System in a ddY Mouse Inhalation Model

The essential oil obtained from Dysphania ambrosioides leaves (DAEO) has antifungal, antioxidant, and antimicrobial properties. This study investigated DAEO's chemical composition and its sleep-promoting effects via administration by inhalation in ddY mice. Ascaridole (35.5%) and p-cymene (47.2%) were the major components. To obtain insight into DAEO's effects on the central nervous system (CNS), ascaridole and p-cymene were evaluated for sedative activity by using the caffeine-treated excitatory mouse model. DAEO administration significantly decreased locomotor activity at all doses except 0.000 04 mg per 400 μL of triethyl citrate. Both ascaridole and p-cymene were highly effective in decreasing locomotor activity of excited mice by more than 50%. In addition, ascaridole and p-cymene prolonged the pentobarbital-induced sleeping duration by 42% and 77%, respectively. These effects were antagonized by coadministration of gamma-aminobutyric acid (GABAA)-benzodiazepine receptor antagonist, flumazenil (3 mg/kg), indicating that the GABAergic system mediates the sedative effect. Finally, inhaled ascaridole and p-cymene had no negative effect on motor coordination, as observed during the Rota-rod test. Therefore, via activation of the GABAergic system, ascaridole and p-cymene mediate the sleep-promoting effect of DAEO. The results further extend the knowledge on their use as potential promising natural products for the management of sleep disorders and CNS-related ailments.