Phytotherapeutic options for the treatment of epilepsy: pharmacology, targets, and mechanism of action

Abstract

Epilepsy is one of the most common, severe, chronic, potentially life-shortening neurological disorders, characterized by a persisting predisposition to generate seizures. It affects more than 60 million individuals globally, which is one of the major burdens in seizure-related mortality, comorbidities, disabilities, and cost. Different treatment options have been used for the management of epilepsy. More than 30 drugs have been approved by the US FDA against epilepsy. However, one-quarter of epileptic individuals still show resistance to the current medications. About 90% of individuals in low and middle-income countries do not have access to the current medication. In these countries, plant extracts have been used to treat various diseases, including epilepsy. These medicinal plants have high therapeutic value and contain valuable phytochemicals with diverse biomedical applications. Epilepsy is a multifactorial disease, and therefore, multitarget approaches such as plant extracts or extracted phytochemicals are needed, which can target multiple pathways. Numerous plant extracts and phytochemicals have been shown to treat epilepsy in various animal models by targeting various receptors, enzymes, and metabolic pathways. These extracts and phytochemicals could be used for the treatment of epilepsy in humans in the future; however, further research is needed to study the exact mechanism of action, toxicity, and dosage to reduce their side effects. In this narrative review, we comprehensively summarized the extracts of various plant species and purified phytochemicals isolated from plants, their targets and mechanism of action, and dosage used in various animal models against epilepsy.

Keywords: antagonist, agonist; anticonvulsive; antiepileptic; epilepsy; phytochemicals; plant extracts.

FIGURE 1

(A) Signs and symptoms of seizure and epilepsy, (B) Approved and Marketed AEDs by USFDA, (C) Different treatment options for the treatment of epilepsy. (Figures were generated using Biorender online version).

FIGURE 2

Various receptors, membrane protein channels, and enzymes involved in the initiation and propagation of seizure and the targets for the current AEDs and future drugs. (Bio-render online version was used for this figure; for abbreviations, please see the list of abbreviations).

FIGURE 3

Phytochemicals can modulate NMDAR and AMPAR in the animal model of epilepsy. (A) Mechanistic overview of the effect of Jujuboside B from medicinal plants against febrile seizures and the mechanism of action on AMPA receptor (Jin et al., 2023). Copyright permission@ Elsevier 2023. (B) apigenin-8-C-glycoside (AP8CG) and Chlorogenic acid (CA) effects on the levels of glutamate and GABA in the hippocampus of mice and their comparison with standard drugs and control group. (C) mRNA profile of NMDAR, mGlu1, and mGLU5 in experimental groups (treated with AP8CG and CA and control groups (Aseervatham et al., 2016). Copyright permission@ Elsevier 2023. (D) A mechanistic overview of the antiepileptic activity of Grewia tiliaefolia in mice followed by in silico analysis of important phytochemical that involved in the modulation of NMDAR. (E) Possible antiepileptic mechanism of Grewia tiliaefolia (Rajput et al., 2023). Copyright permission@ Springer Nature 2023.

FIGURE 4

Schematic representation of the role of VGCCs in epilepsy and pharmacological targets for phytochemicals. (A) Role of Ca⁺² channels in the development of epilepsy. Adopted from (Xu and Tang, 2018). Copyright permission@ MDPI 2018, (B) Possible anti-convulsant mechanism of (B). diffusa on the inhibition of VGCCs. Adopted from (Kaur and Goel, 2011). Copyright permission@ Hindawi 2011. (C) Schematic representation of inhibition of CaV2.3 (R-Type) and CaV2.2 (N-Type) Voltage-Gated Calcium Channels by Physalin F in pain model (Shan et al., 2019). Copyright permission@ ACS 2019.

FIGURE 5

Three states of the VGSCs, i.e., closed, open, and inactivated states (Mantegazza et al., 2010). Copyright permission@ Elsevier 2010.

FIGURE 6

A comprehensive summary of moringa extracts in the rat model of temporal lobe epilepsy (Fayez et al., 2023). Copyright permission@ Elsevier 2023.