In silico molecular modeling, neuro-behavioral profile, and toxicity assessment of the essential oil of Ferula gummosa Boiss. as an anti-seizure agent

Epilepsy is a chronic disease with numerous physical, psychological, cognitive, social, and economic implications, characterized by spontaneous seizures. According to the World Health Organization reports, around 50 million people worldwide have epilepsy, and around 5 million new cases are diagnosed yearly (Adeyemi et al., 2010; Rezvani et al., 2011; Gharib et al., 2018; Kapucu et al., 2020). There are significant challenges in the treatment of epileptic patients with synthetic antiepileptic drugs, including the therapeutic ineffectiveness of these drugs in the treatment of about 30% of cases and also their severe side effects, such as memory impairment, loss of coordination, muscle relaxation, gum hyperplasia, megaloblastic anemia, skin diseases, fatigue, and dizziness. Hence, an antiepileptic agent with minimal side effects and maximal efficacy is needed (da Fonsêca, da Silva Maia Bezerra Filho et al. 2019; Jahani et al., 2020).

Natural products have been an appropriate and rich source of therapeutic agents for the treatment of epilepsy. Ferula gummosa Boiss., known in Persian as “Baridje,” belongs to the Apiaceae family (Jalali et al., 2011; Jalali et al., 2013). It is a perennial herbaceous wild plant endemic to Iran and is distributed widely in its northern and western parts (Jalali et al., 2011; Jalali et al., 2012). All parts of this plant, especially the root, contain galbanum (Enauyatifard et al., 2012; Jalali et al., 2013). Galbanum, the oleo-gum resin of F. gummosa, is one of the essential traditional herbal medicines in Iran applied as a tonic for epilepsy and chorea, memory enhancement, gastrointestinal diseases and wound healing (Adhami et al., 2014; Najafabadi et al., 2017). In addition, it is used in other fields, such as food and beverages, cosmetics, textiles, and jewelry (Jalali et al., 2012; Pavela et al., 2020). Numerous studies have been published on the pharmacological activities of different parts of F. gummosa, including anti-bacterial, antioxidant, anti-convulsion, spasmolytic, and acetylcholinesterase inhibition properties (Adhami et al., 2013, Adhami et al., 2014; Sobhani Najafabadi et al., 2017).

In this paper, we investigated the toxicity, anticonvulsant effects, and molecular modeling of the essential oil (EO) obtained from the oleo-gum resin of F. gummosa in male mice using in vivo (Acute pentylenetetrazole-induced seizure), in vitro (MTT assay), and in silico (molecular dynamics simulation) methods. Its effects on memory, locomotor activity, and motor coordination were also studied.

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