Bioenhanced antiepileptic activity of Ajwain oil microemulsion in Epilepsy treatment using in-vivo zebrafish model

Abstract

Epilepsy is a group of neurological disorders which exhibit periodic seizures. It is a transient<br>neurologic event of paroxysmal abnormal or excessive cortical electrical discharge. It occurs due<br>to an alteration in membrane potential that makes certain neurons abnormally hyperactive and<br>hypersensitive to changes in their neurochemical environment. Epilepsy affects approximately<br>50 million individuals worldwide with India, contributing to almost 6 to 10 million patients. In<br>the search of a promising treatment for epilepsy with minimal side-effects in comparison to<br>existing synthetic drugs, herbal product like Ajowan oil (Trachyspermum ammi, an annual herb<br>belonging to the family Apiaceae) was evaluated in a Pentylenetetrazol (PTZ) induced acute<br>seizure model in zebrafish. The main active constituent in Ajowan oil is thymol (50 – 60%)<br>which is reported to promote GABA responses by stimulating human GABA-A receptors and<br>increasing the chloride ion channel opening, collectively responsible for its antiepileptic action.<br>In our study, Ajowan Oil was formulated as a Microemulsion (ME) for its effortless permeation<br>in brain. The ME was administered orally (11.1mg/kg and 22.2mg/kg) in PTZ induced epileptic<br>zebrafish model and the effect was compared with Diazepam (Standard drug). Ajowan Oil-ME<br>exhibited a significant improvement in epileptic episodes after 30 minutes of dosing as compared<br>to Diazepam with a significant reduction (P<0.001) in erratic movement, tonic-phase and<br>myoclonic jerk time . In conclusion, Ajowan oil ME, administered by a non-invasive oral route,<br>was found to be promising against PTZ induced Epilepsy in zebrafish model, in a dose<br>dependent manner.