# Synthetic Aminochalcone Prevents Hyperglycemia-Induced Anxiety and Delays Pentylenetetrazole-Induced Epileptic Crisis in Adult Zebrafish

## TL;DR

A synthetic aminochalcone compound shows potential in reducing anxiety and delaying seizures in zebrafish, while also lowering blood sugar and oxidative stress.

## Contribution

The study introduces a synthetic aminochalcone with anxiolytic, hypoglycemic, and anticonvulsant properties tested in zebrafish.

## Key findings

- The compound is non-toxic and reduces anxiety by acting on GABA and serotonergic pathways.
- It significantly lowers blood glucose and oxidative stress in hyperglycemic zebrafish.
- At 1.0 mg/mL, it partially reverses pentylenetetrazol-induced seizures.

## Abstract

Neurological disorders are a major contributor to disability-adjusted
life years (DALYs) worldwide, with anxiety and epilepsy being particularly
prevalent. Among them, anxiety is among the top ten diseases and causes
an annual cost of 42.3 billion dollars in the United States. It can
also increase the chance of developing diabetes, regardless of cardiometabolic
and sociodemographic factors. Diabetes, if left uncontrolled for long
periods, can lead to serious health problems and, in 2021, was responsible
for the deaths of 1.6 million people and affected around 10.5% of
the world population. chalcones belong to the class of flavonoid compounds
and have gained prominence in recent years for presenting a wide range
of physiological effects, with similar effects also being found in
the literature when these compounds are synthesized. Therefore, the
work aimed at the synthesis, characterization, toxicological, anxiolytic,
hypoglycemic, and anticonvulsant analysis of the compound 4AAF in
Danio rerio. Initially, amino
chalcone was synthesized employing the Claisen–Schmidt condensation
reaction, and then its toxicity was tested over 96 h at concentrations
of 0.1, 0.5, and 1.0 mg/mL. Subsequently, groups of 6 treated animals
were formed to evaluate their effects in the following tests: light
and dark, novel tank test, open field test, spinning task, anxiolytic
action mechanism via GABA and serotonergic, chronic hyperglycemia,
reactive oxygen species, and pentylenetetrazol-induced seizure. The
compound produced was shown to be nontoxic, and anxiety tests were
promising at concentrations of 0.5 mg/mL, showing that aminochalcone
acts on both the GABA and serotonergic pathways and that it causes
a reduction in the locomotor pattern of the animals. In the context
of hyperglycemia, the concentration of 0.5 mg/mL significantly reduced
blood glucose levels and oxidative stress in the liver, in addition
to causing anxiolytic and sedative behavior. In the seizure test,
the 1.0 mg/mL concentration partially reversed PTZ-induced convulsive
behavior in stage three. Finally, synthetic chalcones have more than
one physiological effect, requiring bioprospecting for other possible
actions, and zebrafish become an interesting model to investigate
their various uses.