Phytoceutical isoquercitrin and ethanolic extracts from pequi (Caryocar coriaceum Wittm) reverse alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio)

Abstract

Pharmacotherapy in Alcohol Withdrawal Syndrome (AWS), which is a mental disorder, generally involves benzodiazepines due to their action via GABA, but their side effects, such as excessive sedation, mental confusion and risk of dependence, are considerable. It is important to investigate the anxiolytic potential of plants such as Caryocar coriaceum, due to the presence of secondary metabolic compounds, such as isoquercitrin, capable of promoting the reduction of anxiety during AWS. We evaluated the anxiolytic-like potential of ethanolic extracts from the leaves (EEPL) and pulp (EEPP) of C. coriaceum, and its major compound, isoquercitrin (IsoQuer), in adult zebrafish (Danio rerio) during alcohol withdrawal. Adult zebrafish (n = 8 per group) were treated (20 µL; p.o) with EEPL, or EEPP or IsoQuer (0.01 or 0.05 or 0.1 or 0.5 or 1.0 mg/mL) and submitted to the 96-hour acute toxicity test. Flumazenil in adult zebrafish and molecular Docking of IsoQuer were used to investigate the GABAergic involvement. Finally, the anxiolytic-like activity was evaluated during alcohol withdrawal in adult zebrafish. The results indicated that EEPL, EEPP and IsoQuer are safe and have no sedative effect on adult zebrafish. Furthermore, they demonstrated a pharmacological potential in the treatment of alcohol withdrawal-induced anxiety, mediated by the GABAergic system, evidenced in the in-silico study by the stable isoquercitrin-GABA_A complex, the main constituent of the extracts. These findings suggest an anxiolytic herbal potential of C. coriaceum and isoquercitrin, providing an alternative for the treatment of anxiety associated with AWS.