UPLC-PDA-ESI-QDA characterization and evaluation of the antioxidant and anxiolytic activities of the ethanolic extract of Sarcomphalus joazeiro (Mart.) Hauenschild leaves

Abstract

Sarcomphalus joazeiro (Rhamnaceae) demonstrated antioxidant activity and effects on the central nervous system (CNS), being considered an alternative for preclinical investigations of anxiolytic drugs. The aim of this study was to evaluate the chemical composition, antioxidant capacity and anxiolytic effect of the ethanolic extract of the leaves of S. joazeiro (EEFSJ). The chemical profile was analyzed by liquid chromatography coupled to mass spectrometry (UPLC-PDA-ESI-QDA). The antioxidant activity was evaluated using DPPH• and ABTS•⁺ capture assays. Acute toxicity tests for 96 h, open field and light/dark tests were applied in vivo to evaluate the sedative and anxiolytic effects, respectively, using zebrafish of both sexes with n = 6/treatment group, at doses of 40, 200 and 400 mg/kg. A total of 5 groups were formed. For the mechanism of action test, the antagonist flumazenil (FMZ) group was also included in the sample. Eleven compounds from the flavonoid and saponin classes were identified. EEFSJ showed a median inhibitory concentration (IC50) of 185.2 ± 2.2 µg/mL and 74.17 ± 1.5 µg/mL against DPPH• and ABTS•⁺ radicals, respectively. At low doses, EEFSJ may have an anxiolytic effect; however, as the doses increase, the sedative effect becomes predominant and no toxicity was observed after 96 h, and its mechanism of action is related to GABAergic modulation. Thus, it is necessary to evaluate the pharmacological profile of EEFSJ in chronic models of anxiety and oxidative stress, as well as to extend the studies to mammals, exploring potential clinical applications and long-term safety.