Anxiolytic and sedative-like effects of flavonoids from Tilia americana var. mexicana: GABAergic and serotonergic participation

Abstract

Introduction. The inflorescences of Tilia americana var. mexicana are used as an infusion in Mexican traditional medicine due to their tranquilizing effects; however, pharmacological and phytochemical studies of the leaves are lacking.

Objective. In this research, the anxiolytic and sedative-like efficacy of the Tilia americana var. mexicana leaves was compared to that obtained with its inflorescences and flavonoids therein identified, as well as the possible mechanism of action.

Methods. The sorted and dried inflorescences and leaves were macerated subsequently in hexane, ethyl acetate and methanol. The methanol extracts were qualitative- and quantitative-analyzed by HPLC, using commercial flavonoids standards selected on the basis of their previously reported presence in Tilia species. The pharmacological activity was evaluated in CD-1 mice in the tests: open-field, elevated plus-maze, hole-board, and the sodium pentobarbital-induced sleep potentiation test. In regard to the mechanism of action, participation of benzodiazepine and 5-HT1A serotonin receptors was tested with the respective antagonists: flumazenil and WAY100635.

Results. The presence of quercetin, rutin and isoquercitrin was confirmed in the extracts of the inflorescences and leaves. The anxiolytic-like effects were the same between the two organs, which were inhibited in the presence of flumazenil and WAY100635.

Discussion and conclusion. Our results provide evidence that the extracts of the leaves of T. americana var. mexicana are as efficacious as the inflorescences to produce anxiolytic and sedative-like effects, where flavonoids like quercetin, rutin and isoquercitrin are partially responsible for these activities by the involvement of GABA/BDZ and 5HT1A serotonergic receptors.