Epilepsy is a complex neurological heterogeneous disorder with diverse etiologies, variable prognosis, and cognitive decline that significantly impact quality of life. The highest prevalence of epilepsy is reported in regions such as sub-Saharan Africa, central Asia, central and Andean Latin America and Southeast Asia (Dorji et al., 2023, Quatraccioni et al., 2024). It is a major cause of morbidity and mortality particularly affecting people (80%) in low- and middle-income countries (Dorji et al., 2023, Devinsky et al., 2018). Most epilepsy cases (75%) start in childhood suggesting the highest vulnerability of brain development and seizures (Stafstrom and Carmant, 2015, Quatraccioni et al., 2024). Clinical manifestations include loss of awareness, mobility abnormalities, sensation (vision, hearing, and taste), mood or cognitive capacities, bruising, and the danger of mortality. Given this, research in developing effective strategies and therapies for the management and treatment of epilepsy remains a central focus and challenge for researchers. Currently, the treatment of epilepsy encompasses medication, surgery, dietary therapy, acupuncture, moxibustion, etc. (Abramov et al., 2022, Waris et al., 2024, He et al., 2024). With about thirty different anti-epileptic drugs available globally, they remain the preferred method for the treatment of epilepsy. These anti-epileptic drugs were reported to cause side effects in 30–45% of the patients treated and nearly a similar number of patients found resistant to these drugs. Other major concerns such as the risk of drug-drug interactions also responsible for the limited clinical applications of these drugs (Belete, 2023, Kwan and Brodie, 2000). This trend highlights the continued efforts for the development of more effective treatment options with low side effects for epilepsy (Kumar et al., 2020, He et al., 2024, Kwan et al., 2010).

Many medicinal plants with therapeutic potential for epilepsy have been documented in ancient literature and considered a safe alternative to pharmaceutical drugs (Kaur et al., 2021, He et al., 2024, Waris et al., 2024). Recent years have witnessed a rapidly increasing number of phytochemicals with significant antiepileptic activities isolated from medicinal plants and their number is on the rise. Despite these advancements, there is still a scarcity of information on the toxicities and applications of these phytochemicals, which has limited their better utilisation. Ferula assafoetida commonly referred to as Hing belongs to the family Apiaceae or Umbelliferae is a well-established plant in South Asian herbal medication. The plant exhibits many useful bioactive properties specifically in combating inflammation and neurological disorders (Shahrajabian et al., 2021, Shojaii and Abdollahi Fard, 2012). Notably, specific compounds present in F. assafoetida including luteolin, ferocolicin, farnesiferol A, eugenol, beta-caryophyllene, coumarin, umbelliferone, myristic acid, farnesol, and ferulic acid have been correlated to anti-inflammatory and neuroprotective properties that could be utilised for the treatment of seizures and related disorders, particularly epilepsy (Sarrafchi et al., 2018, Melnyk et al., 2019). These compounds are believed to influence the pathways and mechanisms involved in epileptogenesis, the onset of epilepsy, and neuronal degeneration (Melnyk et al., 2019, Singh et al., 2006, Alavijeh et al., 2005, Leonti et al., 2002). However, the precise molecular mechanism underlying epileptogenesis and pathophysiology of epilepsy remains poorly understood posing challenges for researchers in the development of more effective treatment options.

In recent years, network pharmacology has emerged as an excellent method for investigating the phytochemical resources and their interactions with target molecules, disease networks and eventually elucidating the mechanisms underlying their pharmacological effects (Marella et al., 2021, Bansal et al., 2022). To date, this technique has been highly successful in uncovering the multi-target effects of medicinal plants in curing a wide range of diseases and disorders and in identifying and categorising novel therapeutic compounds derived from plants. Further, the integration of network pharmacology with molecular docking enhances its capabilities in identifying potential target proteins, pathways and genes influenced by specific phytoconstituents (Carcenac et al., 2015, Lu et al., 2012). Molecular docking provides deeper insights into binding efficiencies and possible inhibitory effects of phytochemicals on disease related targets through modelling molecular-level dynamics (Carcenac et al., 2015, Wang et al., 2017; Florez et al., 2013; Pahal et al., 2021).

This study investigated phytochemicals extracted from F. assafoetida and potential molecular mechanisms underneath its anti-epileptic action utilising a combined approach of network pharmacology and molecular docking. The workflow of the entire methodology from the identification of potent phytochemicals to conducting molecular docking is illustrated in (Fig. 1). To, the best of our knowledge this is the first study of its kind to identify potent anti-epileptic phytoconstituents and elucidate the underlying mechanism for possible alternative complementary treatment for epilepsy using computational methods in tandem with network pharmacology.