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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01249

Embelin protects against pentylenetetrazole-induced seizures and associated memory decline in a zebrafish model.

  • 1University of Montreal Hospital Centre (CRCHUM), Canada
  • 2Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Malaysia
  • 3School of Pharmacy, Monash University Malaysia, Malaysia

Purpose of the research: Epilepsy is a continuous process of neurodegeneration categorized by an enduring tendency to generate uncontrolled electrical firing known as seizures causing involuntery movement all over the body. Cognitive impairment and behavioral disturbances are among the more alarming co-morbidities of epilepsy. Anti-epileptic drugs (AEDs) were found to be successful in controlling epilepsu but are reported to worsen cognitive status in patients. Embelin (EMB) is a benzoquinone derived from the plant Embelia ribes and is reported to have CNS activity. This study aims to evaluate the effectiveness of EMB against pentylenetetrazole (PTZ) induced acute seizures and its associated cognitive dysfunction. This was done via docking studies as well as evaluating neurotransmitter and gene expression in the zebrafish brain.
The principal results: Behavioral observations showed that EMB reduced epileptic seizures and the T-maze study revealed that EMB improved the cognitive function of the fish. The docking study of EMB showed a higher affinity towards gamma-aminobutyric acid (GABAA) receptor as compared to the standard diazepam, raising the possibility of EMB working via the alpha subunit of the GABA receptor. Embelin was found to modulate several genes, neurotransmitters and also neuronal growth, all of which play an important role in improving cognitive status after epileptic seizures. Healthy zebrafish treated with EMB alone were found to have no behavioral and biochemical interference or side effects. The immunohistochemistry data suggested that EMB also promotes neuronal protection and neuronal migration in zebrafish brains.
Major Conclusions: It was perceived that embelin suppresses seizure-like behavior via GABAA receptor pathway and have positive impact on cognitive functions. The observed effect was supported by docking study, T-maze behavior, neurotransmitter & gene expression levels and immunohistology study. The apparatus such as, the T-maze and seizure scoring behavior tank were found to be the straightforward technique to score seizure and test the learning ability after acute epilepsy seizures. These research findings suggest that embelin could be a promising molecule for epilepsy induced learning and memory dysfunction.

Keywords: Embelin, Epilepsy, Cognitive disorder, T-maze behavior, Zebrafish

Received: 13 Jun 2019; Accepted: 27 Sep 2019.

Copyright: © 2019 Kundap, Choo, Kumari, Ahmed, Othman and Shaikh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mohd Farooq Shaikh, Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Bandar Sunway, Kuala Lumpur, Malaysia,