Anxiolytic properties of Cymbopogon citratus (DC.) stapf extract, essential oil and its constituents in zebrafish (Danio rerio).

Ethnopharmacological Relevance: Cymbopogon citratus (DC.) Stapf (Poaceae) leaves is often consumed as infusion in folk medicine due to its therapeutic properties. This plant is also rich in essential oil, which has several beneficial effects to the human health. It is known that medications commonly used to treat anxiety disorders cause undesirable side effects. Thus, it is important to evaluate the anxiolytic effects of natural products from plants, such as C. citratus, as an alternative therapy to treat these disorders.

Objective: The aim of this study was to investigate the anxiolytic properties of C. citratus essential oil (EO), hydroalcoholic extract (E1), citral (CIT), geraniol (GER) and the mixture of these terpenoids, as well as its possible mechanism of action by using zebrafish as an anxiety model.

Methods: Adult zebrafish were treated (by immersion) with C. citratus EO, E1, CIT and/or GER. The anxiolytic effects were analyzed by using the light-dark test. The mechanism involved in the anxiolytic effects was further investigated by the coadministration of flumazenil (FMZ), an antagonist of GABA receptors. The total polyphenols (phenolic and flavonoid compounds) content of E1 was determined by using spectrophotometric assays.

Results: All analyzed samples showed a remarkable anxiolytic effect on zebrafish in the highest concentrations, as the animals showed a preference for the light side of the tank. Furthermore, the observed effect of EO, E1, CIT and GER was reversed by pre-treatment with FMZ, suggesting that GABAergic receptors were involved in the anxiolytic effect displayed by these samples. The association between CIT and GER in the lowest studied concentrations showed an interesting synergistic behavior on anxiolytic effect observed in light-dark test. Besides, it was demonstrated that E1 was constituted by phenolic and flavonoid compounds, which could be involved in the observed effect.

Conclusion: This work has proved that the low-cost zebrafish can be an adequate alternative as an animal model to evaluate the anxiolytic effect of C. citratus and its related compounds. Moreover, the involvement of GABA receptors could be responsible for the effect showed by the samples. These obtained results can potentially validate the ethnopharmacological use of C. citratus as a medicinal plant for the treatment of anxiety disorders in folk medicine.