Exploring antiepileptic phytochemicals of Ferula assafoetida and underlying molecular mechanism using a combined approach of network pharmacology and molecular docking

Abstract

Introduction

Epilepsy is a prevalent and devastating neurological disorder that affects 1–2% of the global population particularly in low- and middle-income countries. There is a growing interest in exploring plant-based alternative therapies for epilepsy as none of the available anti-epileptic drugs provide complete prevention. This study aimed to investigate the bioactive compounds from Ferula assafoetida using computational approach to assess their potential antiepileptic activity and elucidate the mechanisms involved.

Methods

First, phytochemical data was extracted from IMPPAT database and mapped with PubChem. Then obtained their absorption and distribution patterns using SwissADME. Therapeutic targets associated with epilepsy were recognised using Swiss Target Prediction and GeneCards database. The target-network was constructed and performed topological, gene ontology and pathway enrichment analysis. Finally, molecular docking was performed.

Results

Three key bioactive constituents ferocolicin, luteolin, and farnesiferol with potential anti-epileptic activities were identified. These compounds influenced epileptogenesis by targeting proteins GABRA1, GABRA5, GRIN2B, MTOR, PTPRB, and CHRNA4. Molecular docking revealed stable binding of key constituents with three target proteins related to epileptogenesis. The order of binding affinities of the top three compounds to their respective targets was ferocolicin > farnesiferol > luteolin. This suggested a potentially higher therapeutic efficacy and target specificity of these compounds as compared to standard, valproic acid.

Conclusion

F. assafoetida could be utilised in the treatment of epilepsy by modulating epileptogenesis pathways. The study endorsed the importance of the efficacy of multicomponent, multi-target compound therapies decoding new therapeutic targets for epilepsy and related conditions.