Leaves of Spondias mombin L. a traditional anxiolytic and antidepressant: Pharmacological evaluation on zebrafish (Danio rerio)

Abstract

Ethnobotanical relevance: Spondias mombin L. is a plant dispersed throughout the tropical regions of South America, Africa, and Asia, being found mainly in the North and Northeast of Brazil, where the leaves are used in preparations for neuropsychiatric disorders. Therefore, it is of great importance to carry out studies in different pharmacological models that can prove the traditional use of this plant species.

Materials and methods: the hydroethanolic extract from S. mombin leaves (HELSm) was evaluated by oral administration (25 mg/kg) and by immersion (25 mg/l) in scototaxis test in zebrafish (Danio rerio). For this study, caffeine (100 mg/kg) and buspirone (25 mg/kg) were used as standard drugs. The antidepressant action of the HELSm was evaluated assessed in the novel tank diving test (NTDT). In this study, a group with 1% ethanol, one with unpredictable chronic mild stress (UCMS), and another with developmental, social isolation (DSI) were used as induction groups for depression-like behavior and fluoxetine (20 mg/kg) as a drug pattern.

Results: by the HPLC-UV fingerprint analysis, the HELSm presented several derivatives of polyphenolic compounds and flavonoids and identified ellagic acid and isoquercitrin, and by the gas-chromatographic, the majority of the identified compounds were fatty acids, esters, and alcohols. By immersion, the LC₅₀ was 49.86 mg/l and by oral via the LD₅₀ in 48 h, was 4.515 g/kg in zebrafish. For all spatiotemporal and behavioral variables (time spent, white compartment, latency, toggle, erratic swimming, freezing duration, thigmotaxis, and risk assessment), the treatment with HELSm produced a similar effect to buspirone and was significant when compared to the caffeine and control group (p < 0.01, Tukey-Kramer test). For all spatiotemporal and behavioral variables evaluated (time spent at the top of the apparatus, crossed quadrants, erratic swimming, and duration of freezing), treatment with HELSm produced a change in the depression-like behavior in the groups tested, with a similar effect to fluoxetine, both with a significant difference when compared to the control groups (p < 0.01).

Conclusions: Our results suggest that the acute administration of the HELSm in the scototaxis and NTDT tests in a zebrafish model (Danio rerio) produced anxiolytic and antidepressant effects, devoid of hypnotic and sedative actions by immersion, and this action was improved when administered by oral via. Possibly, the presence of isoquercitrin in the leaves of Spondias mombin participates in the anxiolytic and antidepressant effects.

Keywords: Antidepressant; Anxiolytic; Danio rerio; Scototaxis test; Spondias mombin; Zebrafish.