# Anticonvulsant Potential of the Essential Oil of Croton Heliotropiifolius Kunth: In Vivo and In Silico Approach

## TL;DR

This study explores the anticonvulsant effects of an essential oil from Croton heliotropiifolius, showing it may help treat epilepsy by interacting with key brain receptors.

## Contribution

The study combines in vivo and in silico methods to identify anticonvulsant compounds in Croton heliotropiifolius essential oil.

## Key findings

- OCH essential oil increased seizure latency and survival in animals at 200 mg/kg.
- Sesquiterpenes in OCH showed strong binding to GABAA and NMDA receptors.
- Molecular dynamics simulations confirmed stability of key compound-receptor complexes.

## Abstract

Epilepsy is a chronic condition that significantly impacts
the
quality of life of many individuals, underscoring the urgent need
for the identification of safe and effective anticonvulsant agents.
In this context, medicinal plants have emerged as a promising source
of bioactive compounds for treating epilepsy. This study involved
an in vivo and in silico investigation of the anticonvulsant activity
of the essential oil from the leaves of Croton heliotropiifolius Kunth (OCH). In vivo experiments revealed that the essential oil
promoted a significant increase in seizure latency and survival rate
in animals treated with OCH at a dose of 200 mg/kg, indicating an
anticonvulsant effect. To understand the possible receptors and sites
of action of the compounds in the oil, we performed a molecular docking
study with GABAA and NMDA receptors. Additionally, we calculated
the electronic properties of the phytoconstituents at the B3LYP/6–311++G­(d,p)/SMD
level. The results of the molecular docking studies revealed that
the sesquiterpenes α-bulnesene, δ-cadinene, and β-bourbonene,
which are present in OCH, have a high affinity for the GABAA receptor, with binding energies ranging from −10.0 to −9.1
kcal/mol. These compounds primarily interact with the receptors through
hydrophobic forces, highlighting the importance of interaction with
Phe77 of the γ2–(E) subunit of GABAA. Docking analysis of NMDA revealed a higher affinity for the sesquiterpene
guaiadiene, with a binding energy of −8.0 kcal/mol. Molecular
dynamics simulations indicate that the α-bulnesene–GABAA and guaiadiene–NMDA complexes remained stable over
100 ns. DFT analysis revealed that the most promising ligands are
more stable and have moderate to strong electrophilicity. This research
provides valuable insights for the identification of new molecules
in the development of herbal medicines for the treatment of epilepsy,
suggesting that the anticonvulsant effect of OCH may be related to
the modulation of the GABAA receptor or NMDA.