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Abstract

The common neurological condition known as epilepsy is typified by frequent seizures. Despite their effectiveness, traditional antiepileptic medications frequently have negative side effects and resistance problems. Epilepsy affects fifty million individuals globally, accounting for around one-third cases still have uncontrollable seizures and bad drug responses even though there are several antiepileptic medications (AEDs) available. Due to this restriction, there is now more interest in alternative and traditional medicine, especially plant-based treatments, many of which have been practiced for millennia in many different cultures. Using a variety of mechanisms, including GABA modulation, NMDA receptor antagonism, and antioxidant activity, medicinal plants have become popular alternative medicines with anticonvulsant effects. A comprehensive overview of medicinal plants historically utilized for the treatment of epilepsy is what this review attempts to provide, including ethnobotanical knowledge, phytochemical ingredients, pharmacological research, and suggested mechanisms of action. In preclinical and restricted clinical contexts, plants have shown encouraging anticonvulsant and neuroprotective properties.

Keywords

Epilepsy, Traditional plants, Seizures, GABA, AED’s (antiepileptic drugs), Neurotransmission, NMDA, Glutamate, WHO

Introduction

Herbal medicines are often regarded as advantageous compared to conventional antiepileptic drugs due to several factors. Numerous civilizations have long used them traditionally, and hundreds of plant species have been studied for their anticonvulsant qualities

(1) Herbal remedies typically contain multiple bioactive compounds that can act synergistically, targeting different mechanisms such as enhancing GABAergic transmission, inhibiting glutamate release, modulating ion channels, and providing antioxidant effects (1,2,3). This multimodal action may offer broader neuroprotection and seizure control. Additionally, herbal medicines are generally more accessible and affordable, especially in resource-limited settings, and are perceived to have fewer side effects than synthetic drugs (2). However, because most research is based on animal models and preclinical data, there is a dearth of solid clinical evidence supporting the safety and effectiveness of the majority of herbal remedies, despite these possible advantages.  Therefore, evidence-based inspection of herbal medications is necessary (1) and their use should be carefully considered alongside conventional therapies, especially given the variability in herbal preparations and the potential for drug interactions (2,3).

Limitation of conventional drugs

Modern pharmacological treatment primarily involves antiepileptic drugs (AEDs) that act through mechanisms such as enhancing GABAergic inhibition, modulating ion channels, or inhibiting excitatory neurotransmission. While AEDs like phenytoin, valporic acid, carbamazepine, and levetiracetam are commonly used, they are not curative and merely control symptoms (4). Approximately 30% of individuals are deemed pharmaco-resistant, which means that even after taking two or more AEDs, their seizures do not subside (5). Additionally, AEDs often come with adverse effects including sedation, dizziness, cognitive impairment, hepatotoxicity, and teratogenicity (6,7). Tolerance, medication interactions, and a decline in quality of life might result from prolonged use. These limitations have driven researchers and clinicians to explore alternative therapies, especially from natural sources (6)

Epilepsy

The neurological condition known as epilepsy is typified by a predisposition to produce repeated, unprovoked seizures brought on by aberrant brain electrical action. When two or more unprovoked seizures occur more than twenty-four hours apart, or when a single seizure has a significant chance of reoccurring because of an underlying brain problem, a clinical diagnosis is usually made (8). Epilepsy is a condition that affects individuals of all ages and is characterized by a variety of symptoms, such as sensory disturbances, involuntary movements, and altered awareness.

Classification of epilepsy

The classification of epilepsy has evolved significantly, with the International League Against Epilepsy (ILAE) providing the most widely accepted framework. The 2017 ILAE classification introduces a three-level approach (9)

A. Seizure Type Classification

Based on onset:

a. Focal Onset Seizures (start in single hemisphere of the brain only)

  • Aware vs impaired awareness
  • Motor (e.g., automatisms, tonic, clonic) or non-motor (e.g., cognitive sensory)

b. Generalized Onset Seizures (start in both hemispheres simultaneously)

  • Motor: clonic, tonic-clonic, tonic, atonic, myoclonic
  • Non-motor: Absence seizures (atypical, typical)

c. Unknown Onset Seizures

  • When onset is not observed or unknown

B. Epilepsy Type Classification

Based on seizure type and EEG/imaging:

  • Focal epilepsy
  • Generalized epilepsy
  • Combined generalized and focal epilepsy
  • Unknown epilepsy

C. Epilepsy Syndrome Classification

An Epilepsy syndrome is the cluster of features (e.g., age of onset, types of seizures, EEG pattern, genetics). Examples: Childhood absence epilepsy, Juvenile myoclonic epilepsy, Lennox-Gastaut syndrome.

Mechanism of action

Herbal plants exert their anticonvulsant effects through several detailed mechanisms that target the underlying neurobiology of epilepsy. The major mechanisms of action identified in recent research include

  1. Inhibition of Excitatory Glutamatergic Transmission

Some plant extracts inhibit the glutamate release or antagonize NMDA receptors, reducing excitatory neurotransmission that can trigger seizures. For example, Lavandula officinalis inhibits glutamate release and blocks calcium channels, while Panax ginseng inhibits NMDA receptor-mediated calcium influx (1,10,11)

  1. Inhibition of Cation Channels and Reduction of Membrane Excitability

Many herbal anticonvulsants reduce neuronal excitability by inhibition of voltage-gated Na+, K+, or calcium channels. This action stabilizes neuronal membranes and diminishes the likelihood of abnormal, excessive firing that leads to seizures (12)

  1. Anti-inflammatory and Immunomodulatory Actions

Chronic Neuroinflammation contributes to seizure susceptibility and epileptogenesis. Certain herbal medicines suppress inflammatory mediators and modulate immune responses in the brain, providing neuroprotection and reducing seizure frequency (1,10,11)

  1. Antioxidant and Mitochondrial Protective Effects

The pathophysiology of epilepsy is linked to mitochondrial malfunction and oxidative stress.  Strong antioxidant qualities found in herbal substances help shield neurons from seizure-induced damage by scavenging free radicals and enhancing mitochondrial activity (10,11)

  1. Enhancement of GABAergic Neurotransmission

The main inhibitory neurotransmitter in the brain, gamma amino butyric acid (GABA), is enhanced by a large range of chemicals produced from plants. They may act as GABA receptor agonists or positive allosteric modulators, thereby increasing inhibitory synaptic transmission and suppressing seizure activity (1,10)

  1. Regulation of Protein Synthesis and Cellular Metabolism

Some herbal compounds modulate protein synthesis, autophagy, and metabolic pathways, which can influence neuronal survival and excitability. This includes effects on pathways such as PI3K/Akt/GSK-3 and mTOR signaling, which are involved in cell growth, survival, and neuroprotection (1,10,11)

Fig 1: Mechanism of action of some herbal plants exhibiting antiepileptic activity

Influence of Traditional Plants and Medicines

Medicinal plants are increasingly recognized for their significant role in epilepsy management, owing to their broad-spectrum therapeutic properties, favorable safety profiles, and accessibility. Numerous phytochemicals and plant extracts have exhibited anticonvulsant activity in preclinical models by modulating critical targets such as gamma-aminobutyric acid (GABA) receptors, N-Methyl-D-aspartate (NMDA) receptors, and various ion channels implicated in seizure initiation and propagation. These compounds often exert multifaceted effects, including the regulation of excitatory and inhibitory neurotransmission, antioxidant activity, and anti-inflammatory responses, thereby contributing to their neuroprotective potential. Compared to conventional antiepileptic drugs, medicinal plants are typically more cost-effective, widely available, and associated with fewer adverse effects, making them particularly advantageous in low- and middle-income countries with limited access to modern pharmacotherapy. Despite promising preclinical outcomes, further research is necessary to elucidate their precise mechanisms of action, establish standardized dosages, and ensure clinical safety. The World Health Organization has endorsed the integration of plant-based medicines into healthcare systems due to their therapeutic efficacy and reduced risk profiles. Notably, cannabidiol (CBD), a phytochemical derived from Cannabis indica, has received regulatory approval for the treatment of certain severe epileptic syndromes, underscoring the potential of plant-derived compounds in epilepsy therapy. Overall, medicinal plants represent a valuable and underutilized resource in the development of safer, effective, and accessible treatment options for epilepsy. (12,13,14,15).

Prevalence and Epidemiology of Epilepsy

Systematic reviews and meta-analyses estimate the global point prevalence of active epilepsy at approximately 6.4 per 1,000 individuals, with a lifetime prevalence of around 7.6 per 1,000. The annual cumulative incidence is reported at 67.8 per 100,000 individuals, while the incidence rate stands at roughly 61.4 per 100,000 person-years. These epidemiological indicators are significantly elevated in low- and middle-income countries (LMICs), where the median incidence reaches 81.7 per 100,000, in contrast to 45.0 per 100,000 observed in high-income countries (HICs). This disparity is largely attributed to inadequate healthcare infrastructure, a higher burden of central nervous system infections, and an increased prevalence of perinatal complications in LMICs. (16,17)

Globally, the burden of epilepsy is most pronounced in regions such as Africa and Latin America, with the highest incidence rates observed in the Middle East and Latin America. Current estimates indicate that approximately 51.70 million individuals are living with active epilepsy worldwide. Moreover, around 4.6 million new cases are reported annually, highlighting the substantial and ongoing public health challenge posed by this neurological disorder.(18)

Fig 2: World map of the prevalence and epidemiology of active epilepsy by WHO (18)

Epilepsy and Phytotherapy

Phytotherapy, the use of medicinal plants for therapeutic purposes, has gained attention as a complementary or alternative strategy for epilepsy management, particularly in cases where conventional antiepileptic drugs (AEDs) prove ineffective or elicit significant side effects. Approximately one-third of individuals with epilepsy fail to achieve complete seizure control with standard pharmacological treatments, leading to increased interest in traditional herbal remedies. (19,20). Several plants, including Carum carvi L. and Punica granatum, have demonstrated anticonvulsant and sedative effects, likely mediated through modulation of GABAergic neurotransmission (20). Similarly, herbs such as Ocimum sanctum and Citrus sinensis, commonly used in traditional Indian medicine, exhibit neuroprotective and seizure-modulating properties through antioxidant activity and GABA-mimetic mechanisms (21). Recent studies have also emphasized the therapeutic potential of cannabidiol (CBD), a phytochemical derived from Cannabis sativa, in managing drug-resistant epilepsy syndromes like Dravet syndrome, primarily through its influence on the endocannabinoid system and neuronal excitability (22). These medicinal plants are rich in diverse bioactive constituents—such as flavonoids, alkaloids, and terpenoids—which are thought to underlie their anticonvulsant and anti-inflammatory actions (23). Despite promising preliminary findings, further well-designed clinical trials and efforts toward standardization are crucial to validate the efficacy and safety of plant-based interventions in epilepsy treatment.

Table 1: Plants with Reported Antiepileptic Activity: Family, Parts Used, and Bioactive Compounds (24-69)

Biological Name

Family

Parts

Active constituents

Acalypha indica

Euphorbiaceae

Aerial part

Alkaloids, Terpenoids, Flavonoids

Allium cepa L.

Liliaceae

Bulb

Alkaloids, flavonoids, phytosterols

Annona senegalenesis

Annonaceae

Leaf

Acetogenins, alkaloids, flavonoids, terpenes, saponins

Arenaria kansuensis

Caryophyllaceae

Whole Plant

Flavonoids

Artemisia Persia

Asteraceae

Whole Plant

Flavonoids and phenols, Artemisinin

Asterothamnus centrali-asiaticus

 

Whole Plant

Flavonoids

Biophytum umbraculum

Oxalidaceae

Root

Flavonoids, phenols, tannins, steroids, terpenoids

Butea monosperma

Fsabaceae

Stem

Flavonoids and steroids

Calotropis procera

Apocynaceae

Leaf

Alkaloids, saponins, and sterols

Canarium schweinfurthii

Burseraceae

Stem

Flavonoids, sterols, phenols

Cannabis sativa

Cannaceae

Aerial part

Cannabinoids, terpenes, flavonoids

Carissa edulis

Apocynaceae

Root

Anthraquinone, tannins, saponins, flavonoids

Carum carvi L

Apiaceae

Seed

Tannins, alkaloids, and terpenoids

Azima Tetracantha

salvadoraceae

Root

Alkaloids, flavonoids, glycosides, terpenoids

Citrullus colocynthis

Curcurbitaceae

Fruit

Glycosides, flavonoids, alkaloids

Citrus Sinensis

Rutaceae

Leaf

Flavonoids, essential oils, phenolic acids

Clerodendrum viscosum

Verbenaceae

Leaf

Flavonoids, terpenes and phenols

Cocos nucifera L.

Arecaeae

Root

Phenols, amino acids, medium chain fatty acids

Combretum micranthum

Combretaceae

Root

Flavonoids , saponins, tannins, terpenoids

Commiphora wightii

Burseraceae

Resin

Guggulsterones, terpenoids, flavonoids, polyphenols

Datura stramonium

Solanaceae

Leaf

Flavonoids, alkaloids, steroids and saponins

Evolvulus alsinoides

Convolvulaceae

Aerial Part

Flavonoids, phenols, tannins, steroids, terpenoids

Ficus abutilifolia

Moraceae

Root

Flavonoids , saponins, tannins, terpenoids

Ganoderma lucidum

Ganodermataceae

Mycelium

Triterpenoids, alkaloids, flavonoids, phenols

Grewia tiliifolia

Tiliaeceae

Aerial Part

Phenols, flavonoids, alkaloids, steroids and saponins

Ipomoea reniformis

Convolvulaceae

Leaf

Phenols, flavonoids, alkaloids, steroids and saponins

Lavandula dental L

Lamiaceae

Leaf

Flavonoids, terpenoids, phenols

Nelumbo nucifera

Nymphaeaceae

Fruit

Flavonoids, alkaloids, saponins, tannins

Ganoderma curtisii

Ganodermataceae

Mycelium

Triterpenoids, alkaloids, steroids, flavonoids

Madhuca longifolia

Sapotaceae

Wood

Alkaloids, flavonoids, terpenoids, saponins

Marsilea quadrifolia

Marsileaceae

Leaf

Polyphenols, flavonoids

Matricaria reticulate

Asteraceae

 

Flower

Phenols, flavonoids, alkaloids

Milicia excels

Moraceae

Leaf

Phenols, flavonoids, alkaloids

Nardostachys jatamansi

Caprifoliaceae

Root

Sesquiterpenes, alkaloids, phenols, flavonoids

Ocimum sanctum

Lamiaceae

Leaf

Flavonoids, alkaloids, tannins, steroids, glycosides,

Pergularia daemia

Asclepiadaceae

Root

Cardenolides, phenols, alkaloids, flavonoids

Phyllanthus amarus

Euphorbiaceae

Aerial Part

Lignin, glycosides, tannins, steroids, and phenol

Ocimum basilicum

Lamiaceae

Leaf

Phenolics, flavonoids, alkaloids, tannins, steroids

Pseudospondias macrocarpa

Anacardiaceae

Leaf

Alkaloids, phenols, flavonoids

Punica granatum

Punicaceae

Leaf

Polyphenols, flavonoids

Bupleuri Radix

Apiaceae

Root

Saikosaponin, tannins

Rosmarinus officinalis L

Labiatae

Leaf

Alkaloids, phenols, flavonoids, essential oil

Silybum marianum

Asteraceae

Seed

Flavonoid, alkaloids, phenols

Terminalia chebula

Combretaceae

Fruit

Tannins, flavonoids

Aloe vera

Asphodelaceae

Leaf

Anthraquinones,  Polysaccharides,  Saponins, flavonoids

Uncaria rhynchophylla

Rubiaceae

Aerial Parts

Alkaloids, triterpenoids, coumarins, glycosides

Vateria indica

Dipterocarpaceae

Bark

Flavonoids, phenolics, tannins, saponins

Viola tricolor

Violaceae

Leaf

Flavonoids, saponins, anthocyanin, coumarins,

Vitex negundo

Verbenaceae

Leaf

Flavonoids, phenolics, tannins, saponins

Withania coagulans

Solanaceae

Fruit

Alkaloids, flavonoids, tannins

Table 2: Plants with Antiepileptic Potential: Mechanistic Approaches and In-Vivo Evaluation Models (24-69)

Biological Name

MOA

Animal Model

Acalypha indica

Enhanced GABA levels in neurons

MES & PTZ model in Mice

Allium cepa L.

Modulates GABA receptors

MES & PTZ  model in Mice

Aloe vera

Inhibit NMDA-induced retinal ganglionic cell apoptosis

MES & PTZ model in Mice

Annona senegalenesis

Enhance GABAergic neurotransmission

PTZ model in Rats

Arenaria kansuensis

Binds benzodiazepine site of  GABAA

PTZ model in Mice

Artemisia Persia

Reduces oxidative stress and inflammation (IL-1β, TNF-α inhibition)

PTZ model in Mice

Asterothamnus centrali-asiaticus

Binds GABAAR; anticonvulsant activity

PTZ model in Mice

Azima Tetracantha

Antagonizes the inhibitory GABAergic neurotransmission and Ca+ channel blockade

MES & PTZ model in Mice

Biophytum umbraculum

Increase in GABAergic neurotransmission

MES& PTZ model in Mice

Bupleuri Radix

NMDA receptor inhibition; mTOR pathway modulation

PTZ model in Rats

Butea monosperma

GABA mediated synaptic inhibition

MES& PTZ model in Mice

Calotropis procera

Activation of the GABAergic neurotransmittion

PTZ , picrotoxin, & strychnine-model

Canarium schweinfurthii

Prolonging the inactivation of sodium channels and  modulate GABAA receptor complex

PTZ, MES  model in Mice

Cannabis sativa

Modulates GABA receptors

Phenobarbitone & PTZ model in Mice

Carissa edulis

Enhancing GABAergic neurotransmission action

MES,INH, PTZ model in Mice

Carum carvi L

Modulation of the GABAergic system

PTZ model model in Mice

Citrullus colocynthis

Modulating the activity of GABA receptor complex

PTZ model in Mice

Citrus Sinensis

Enhances GABAergic activity

PTZ model in Mice

Clerodendrum viscosum

Blocking sodium channel

MES model in Mice

Cocos nucifera L.

Voltage dependent Na+ channel blockage

MES PTZ model in Mice

Combretum micranthum

Ion channel modulation

MES model

Commiphora wightii

Modulation of ion channel and GABAergic neurotransmission

PTZ model in Mice

Datura stramonium

Modulation of gamma-aminobutyric acid (GABA) and (5-HT) receptors

PTZ model in Mice

Evolvulus alsinoides

GABAergic modulation; antioxidant

PTZ model in Mice

Ficus abutilifolia

Ion channel modulation

MES model

Ganoderma curtisii

Stimulation of  GABAergic neurotransmission

Kainic acid, PTZ, Strychnine model

Ganoderma lucidum

Stimulation of  GABAergic neurotransmission

Kiana acid, PTZ, Strychnine

Grewia tiliifolia

GABA receptor agonist; NMDA receptor

PTZ model

Ipomoea reniformis

Restoring the GABA level

MES, PTZ, INH models

Lavandula dental L

Stimulation of  GABAergic neurotransmission

PTZ model in Mice

Madhuca longifolia

Na+ channel blockage, NMDA blockage, Ca2+ channel blockage or by Modulation GABA receptors

MES, PTZ

Lithium- pilocarpine model in Mice

Marsilea quadrifolia

Antioxidant; GABAergic modulation

PTZ  model in Rats

Matricaria reticulate

GABA receptor modulation; anti-inflammatory

PTZ model in Mice

Milicia excels

Blocking the presynaptic inhibition mediated by GABA

PTZ model in Mice

Nardostachys jatamansi

Enhancement of GABAergic Activity

PTZ & MES induces seizure in Rats

Nelumbo nucifera

Modulates GABA receptors

Strychnine seizure model in Mice

Ocimum basilicum

GABAergic modulation

PTZ model model in zebra fish

Ocimum sanctum

NMDA receptor antagonism

MES model in Rats

Pergularia daemia

↑ GABA (240%), ↓ GABA-T activity; anti-inflammatory, antioxidant

PTZ  model in Mice

Phyllanthus amarus

Modulates GABA receptors

PTZ model in Mice

Pseudospondias macrocarpa

Targets GABAergic, NMDA, K+ channels, and nitric oxide pathways

Multiple seizure model in Mice

Punica granatum

Antioxidant; GABA modulation

MES induces seizure in Mice

Rosmarinus officinalis L

Enhancement of GABAergic Activity

Kainic Acid model in Mice

Silybum marianum

Modulates Ion channels

PTZ model in Mice

Terminalia chebula

Decrease in synaptic release  NMDA or glutamate

MES, PTZ model in Rats

Uncaria rhynchophylla

NMDA receptor inhibition; Na+ channel modulation

Pilocarpine model in rat

Vateria indica

Increases GABA levels (via L-glutamate decarboxylase activation); antioxidant effects

MES, INH, PTZ models in Mice

Viola tricolor

Modulation of  GABAA  receptors.

PTZ& MES model in Mice

Vitex negundo

Modulating GABAergic pathways and blocking sodium (Na) channels

MES model in Mice

Withania coagulans

Inhibition of  Na+ channels,  GABAA receptor agonists

MES,PTZ & Strychnine Model in Mice

CONCLUSION

The exploration of traditional medicinal plants as antiepileptic agents has unveiled a diverse pharmacopeia of botanicals with promising anticonvulsant potential, as substantiated by a growing body of experimental evidence, particularly from animal models. This review underscores the therapeutic relevance of several key plants. The mechanisms identified include enhancement of GABAergic transmission, inhibition of glutamatergic excitotoxicity, modulation of ion channels (Na?, Ca²?), antioxidant activity, and anti-inflammatory effects critically involved in the pathophysiology of epilepsy.

The active constituents D-limonene, carvone, alpha-pinene, linalool of carum carvi L has shown promising antiepileptic effect. The (S)-(+)-carvone has increases the latency of the convulsion and cyanocarvone, increases the activity of acetylcholinesterase enzyme that blocks voltage gated Na+ channel which reduces the nerve excitability with modulation of GABAergic system, whereas linalool have direct interaction with NMDA receptor complex also modifies acetylcholine mechanism.

Animal studies have provided compelling evidence of these plants' ability to delay seizure onset, reduce seizure severity, and prolong survival in chemically or electrically model models. Moreover, phytochemicals such as flavonoids, alkaloids, and terpenes found in these plants are believed to contribute synergistically to their anticonvulsant effects. Despite these promising findings, a translational gap remains between traditional knowledge, preclinical validation, and modern clinical application. The variability in plant extracts, lack of standard dosing protocols, and limited human trials present ongoing challenges. Future research should prioritize the isolation of active compounds, elucidation of precise molecular targets, and rigorous clinical evaluations to develop safe, standardized, and effective phototherapeutics for epilepsy.

In conclusion, traditional medicinal plants offer a valuable, underexplored resource for antiepileptic drug development. Integrating ethnobotanical knowledge with modern pharmacological research holds the potential to expand therapeutic options, particularly for individuals with drug-resistant epilepsy or those seeking complementary approaches to seizure management.

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  33. Obese E, Biney RP, Henneh IT, Adakudugu EA, Anokwah D, Agyemang LS, et al. The anticonvulsant effect of hydroethanolic leaf extract of Calotropis procera (Ait) R. Br. (Apocynaceae). Neural Plast. 2021;2021:5566890.
  34. Kandeda AK, Taiwe GS, Ayissi RE, Moutchida C. An aqueous extract of Canarium schweinfurthii attenuates seizures and potentiates sleep in mice: Evidence for involvement of GABA pathway. Biomed Pharmacother. 2021 Oct 1;142:111973.
  35. Ehigiator BE, Mobisson SK, Wopara I, Chibuife CC, Uwaezuoke CA, Eruotor HO. Cannabis sativa: A remedy for convulsion by inhibition of GABAA receptor and significantly delayed onset of seizure latency and death—an experimental validation and molecular docking. J Angiother. 2021;5(1):207–17.
  36. Ya’u J, Yaro AH, Malami S, Musa MA, Abubakar A, Yahaya SM, et al. Anticonvulsant activity of aqueous fraction of Carissa edulis root bark. Pharm Biol. 2015 Sep 2;53(9):1329–38.
  37. Showraki A, Emamghoreishi M, Oftadegan S. Anticonvulsant effect of the aqueous extract and essential oil of Carum carvi L. seeds in a pentylenetetrazol model of seizure in mice. Iran J Med Sci. 2016 May;41(3):200.
  38. Mehrzadi S, Shojaii A, Pur SA, Motevalian M. Anticonvulsant activity of hydroalcoholic extract of Citrullus colocynthis fruit: involvement of benzodiazepine and opioid receptors. J Evid Based Complementary Altern Med. 2016 Oct;21(4):NP31–5.
  39. Nagula JB, Reddy NL. Evaluation of antiepileptic property of Citrus sinensis (leaf extract) by pentylenetetrazol (PTZ) induced convulsions in mice. Sch J App Med Sci. 2017;5(7):2830–5.
  40. Rath M, Bhattacharya A, Santra S, Rath K, Ghosh G, Nanda BB. Neuropharmacological effects of methanolic extract of Clerodendrum viscosum leaves on Wistar albino rats. Pharmacogn Mag. 2018;14(59s).
  41. Archana B, Mudavath RN, Enumula V, Ravali N, Kumar PS. Evaluation of antiepileptic activity of flowers of Cocos nucifera L. against experimentally induced convulsions in rats. J Drug Deliv Ther. 2021 Dec 27;11(6):159–66.
  42. Danmalam UH, Agunu A, Abdurahman EM, Ilyas N, Magaji MG, Yaro AH. Anticonvulsant studies on a traditional antiepileptic mixture used by the Hausa people of north-western Nigeria. Res J Pharmacogn. 2017 Jul 1;4(3):13–9
  43.  Sridhar V, Seetharaman A, Jayakumar P, Jaikumar S. Anticonvulsant activity of oleogum resin extract of Commiphora wightii against pentylenetetrazole-induced convulsion in mice. Int J Pharm Ther. 2016;7(2):53–6.
  44. Namvar Aghdash S, Nasirifard S. The effect of aqueous Datura stramonium L. seed extract on chemical kindling induced by intraperitoneal injection of pentylenetetrazole in mice. Neurosci J Shefaye Khatam. 2015 Jun 10;3(2):35–40.
  45. Venkatesan PS, Sundaresan S, Eswarya M, Madhavaselvi M, Renuka R. Evaluation of antiepileptic properties of herbal mix of different combinations by PTZ-induced mouse model. Phytomed Plus. 2025 May 1;5(2):100773.
  46.  Núñez-Urquiza V, Villeda-Hernández J, Montiel-Arcos E, Tello I, Campos-Peña V, Herrera-Ruiz M, et al. Evaluation of the anticonvulsant, anxiolytic, sedative, and neuroprotective activities of polysaccharides from mycelium of two Ganoderma species. Pharmacogn J. 2021;13(5).
  47. Rajput A, Sharma P, Kumar N, Singh H, Singh T, Singh S, et al. Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole-induced epilepsy: insights from in vivo and in silico studies. Metab Brain Dis. 2023 Oct;38(7):2355–67.
  48. Commune KI, Jaikumar S. Anticonvulsant herb Ipomoea reniformis—a novel approach in the screening of natural product-based anticonvulsant drug against experimentally induced convulsion in Wistar rats.
  49. Antar A, Abdel-Rehiem ES, Al-Khalaf AA, Abuelsaad AS, Abdel-Gabbar M, Shehab GM, et al. Therapeutic efficacy of Lavandula dentata oil and ethanol extract in regulation of neuroinflammation, histopathological alterations, oxidative stress, and restoring balance of Treg cells expressing FoxP3+ in a rat model of epilepsy. Pharmaceuticals. 2024;18(1):35.
  50. Thakare CV, Upasani CD. Madhuca longifolia water extract revealed protective effect against MES, PTZ and Li-pilocarpine induced epilepsy.
  51. Mohanty I, Patri M. Neuroprotective efficacy of Marsilea quadrifolia leaf extract against pentylenetetrazole-model in rat model of epilepsy. Psychol Neurosci. 2024 Sep;17(3):143.
  52. Kazemi M, Ardjmand A, Shahaboddin ME, Mehrand M, Banitaba-Bidgolia SM, Ghavipanjeh G. Effects of hydroalcoholic extract of Matricaria recutita L. on lipid peroxidation and nitric oxide in pentylenetetrazole-kindled mice. Iran J Pharm Sci. 2021;17(2):37–50.
  53. Akinpelu LA, Akanmu MA, Obuotor EM. Mechanism of anticonvulsant effects of ethanol leaf extract and fractions of Milicia excelsa (Moraceae) in mice. J Pharm Res Int. 2018;23(4):1.
  54. Mansuri S, Alex T, Chaudhary S. Comparative study of phenytoin sodium and ethanolic extract of Nardostachys jatamansi augmented with phenytoin sodium to evaluate anti-epileptic activity of the drug. J Drug Deliv Ther. 2017;7(7):218–9.
  55. Rajput MA, Khan RA, Assad T. Anti-epileptic activity of Nelumbo nucifera fruit. Metab Brain Dis. 2017 Dec;32:1883–7.
  56. Batista FL, de Araújo SM, de Sousa DB, Sobrinho FB, de Lima Silva MG, de Oliveira MR, et al. Anticonvulsant and anxiolytic-like potential of the essential oil from Ocimum basilicum Linn leaves and its major constituent estragole on adult zebrafish (Danio rerio). Neurochem Int. 2024 Sep 1;178:105796.
  57. Gupta M, Singh A, Singh S, Sagar BP. Pharmacological evaluation and comparison of anti-epileptic activity of Ocimum basilicum Linn and Ocimum sanctum Linn in albino rats.
  58. Kandeda AK, Moto FC, Ayissi RE, Omam JP, Ojong L, Bum EN. Pergularia daemia hydro-ethanolic extract protects against pentylenetetrazole kindling-model, oxidative stress, and neuroinflammation in mice. J Ethnopharmacol. 2021 Oct 28;279:114338.
  59. Tao Z, Chun-Yan H, Hua P, Bin-Bin Y, Xiaoping T. Phyllathin from Phyllanthus amarus ameliorates epileptic convulsion and kindling-associated post-ictal depression in mice via inhibition of NF-κB/TLR-4 pathway. Dose Response. 2020 Jul 31;18(3):1559325820946914.
  60. Adongo DW, Mante PK, Kukuia KK, Biney RP, Boakye-Gyasi E, Benneh CK, et al. Anticonvulsant activity of Pseudospondias microcarpa (A. Rich) Engl. hydroethanolic leaf extract in mice: the role of excitatory/inhibitory neurotransmission and nitric oxide pathway. J Ethnopharmacol. 2017 Jul 12;206:78–91.
  61. Dhakal K, Chaudhary K, Paudel S, Pant M, Adhikari C, Raj R, et al. Assessment of antioxidant, anti-epileptic and anti-anxiety activities of pomegranate leaf (Punica granatum) in mice. Asian J Pharm Pharmacol. 2021;7(2):58–62.
  62. Rahbardar MG, Hosseinzadeh H. Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders. Iran J Basic Med Sci. 2020 Sep;23(9):1100.
  63. Waqar H, Khan HM, Anjum AA. Antiepileptic potential of Silybum marianum seeds in pentylenetetrazol-induced kindled mice. Bangladesh J Pharmacol. 2016 Jun 12;11(3):603–9.
  64. Kumar R, Arora R, Agarwal A, Gupta YK. Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats. J Ethnopharmacol. 2018 Apr 6;215:124–31.
  65. Shao H, Yang Y, Mi Z, Zhu GX, Qi AP, Ji WG, et al. Anticonvulsant effect of rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy. Neuroscience. 2016 Nov 19;337:355–69.
  66. Alshabi AM, Shaikh IA, Asdaq SM. The antiepileptic potential of Vateria indica Linn in experimental animal models: effect on brain GABA levels and molecular mechanisms. Saudi J Biol Sci. 2022 May 1;29(5):3600–9.
  67. Rahimi VB, Askari VR, Hosseini M, Yousefsani BS, Sadeghnia HR. Anticonvulsant activity of Viola tricolor against seizures induced by pentylenetetrazol and maximal electroshock in mice. Iran J Med Sci. 2019 May;44(3):220.
  68. Kumar R, Bais S. Anti-epileptic activity of casticin phytoconstituent from Vitex negundo on validated animal model. J Drug Deliv Ther. 2024 Dec 1;14(12).
  69. Khattak ZF, Ansari B, Jamal M, Awan AA, Sherkheli MA, ul Haq R. Anticonvulsant activity of methanolic extract of Withania coagulans in mice. Metab Brain Dis. 2021 Dec;36:2437–43.

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  31. Ye M, Bi YF, Ding L, Zhu WW, Gao W. Saikosaponin A functions as anti-epileptic effect in pentylenetetrazol-induced rats through inhibiting mTOR signaling pathway. Biomed Pharmacother. 2016 Jul 1;81:281–7.
  32. Das MK, Mazumder PM, Das S. Antiepileptic activity of methanol extract of Butea monosperma (Lam.) Kuntze and its isolated bioactive compound in experimentally induced convulsion in Swiss albino mice. J Pharm Sci Res. 2015 Dec 1;7(12):1066.
  33. Obese E, Biney RP, Henneh IT, Adakudugu EA, Anokwah D, Agyemang LS, et al. The anticonvulsant effect of hydroethanolic leaf extract of Calotropis procera (Ait) R. Br. (Apocynaceae). Neural Plast. 2021;2021:5566890.
  34. Kandeda AK, Taiwe GS, Ayissi RE, Moutchida C. An aqueous extract of Canarium schweinfurthii attenuates seizures and potentiates sleep in mice: Evidence for involvement of GABA pathway. Biomed Pharmacother. 2021 Oct 1;142:111973.
  35. Ehigiator BE, Mobisson SK, Wopara I, Chibuife CC, Uwaezuoke CA, Eruotor HO. Cannabis sativa: A remedy for convulsion by inhibition of GABAA receptor and significantly delayed onset of seizure latency and death—an experimental validation and molecular docking. J Angiother. 2021;5(1):207–17.
  36. Ya’u J, Yaro AH, Malami S, Musa MA, Abubakar A, Yahaya SM, et al. Anticonvulsant activity of aqueous fraction of Carissa edulis root bark. Pharm Biol. 2015 Sep 2;53(9):1329–38.
  37. Showraki A, Emamghoreishi M, Oftadegan S. Anticonvulsant effect of the aqueous extract and essential oil of Carum carvi L. seeds in a pentylenetetrazol model of seizure in mice. Iran J Med Sci. 2016 May;41(3):200.
  38. Mehrzadi S, Shojaii A, Pur SA, Motevalian M. Anticonvulsant activity of hydroalcoholic extract of Citrullus colocynthis fruit: involvement of benzodiazepine and opioid receptors. J Evid Based Complementary Altern Med. 2016 Oct;21(4):NP31–5.
  39. Nagula JB, Reddy NL. Evaluation of antiepileptic property of Citrus sinensis (leaf extract) by pentylenetetrazol (PTZ) induced convulsions in mice. Sch J App Med Sci. 2017;5(7):2830–5.
  40. Rath M, Bhattacharya A, Santra S, Rath K, Ghosh G, Nanda BB. Neuropharmacological effects of methanolic extract of Clerodendrum viscosum leaves on Wistar albino rats. Pharmacogn Mag. 2018;14(59s).
  41. Archana B, Mudavath RN, Enumula V, Ravali N, Kumar PS. Evaluation of antiepileptic activity of flowers of Cocos nucifera L. against experimentally induced convulsions in rats. J Drug Deliv Ther. 2021 Dec 27;11(6):159–66.
  42. Danmalam UH, Agunu A, Abdurahman EM, Ilyas N, Magaji MG, Yaro AH. Anticonvulsant studies on a traditional antiepileptic mixture used by the Hausa people of north-western Nigeria. Res J Pharmacogn. 2017 Jul 1;4(3):13–9
  43.  Sridhar V, Seetharaman A, Jayakumar P, Jaikumar S. Anticonvulsant activity of oleogum resin extract of Commiphora wightii against pentylenetetrazole-induced convulsion in mice. Int J Pharm Ther. 2016;7(2):53–6.
  44. Namvar Aghdash S, Nasirifard S. The effect of aqueous Datura stramonium L. seed extract on chemical kindling induced by intraperitoneal injection of pentylenetetrazole in mice. Neurosci J Shefaye Khatam. 2015 Jun 10;3(2):35–40.
  45. Venkatesan PS, Sundaresan S, Eswarya M, Madhavaselvi M, Renuka R. Evaluation of antiepileptic properties of herbal mix of different combinations by PTZ-induced mouse model. Phytomed Plus. 2025 May 1;5(2):100773.
  46.  Núñez-Urquiza V, Villeda-Hernández J, Montiel-Arcos E, Tello I, Campos-Peña V, Herrera-Ruiz M, et al. Evaluation of the anticonvulsant, anxiolytic, sedative, and neuroprotective activities of polysaccharides from mycelium of two Ganoderma species. Pharmacogn J. 2021;13(5).
  47. Rajput A, Sharma P, Kumar N, Singh H, Singh T, Singh S, et al. Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole-induced epilepsy: insights from in vivo and in silico studies. Metab Brain Dis. 2023 Oct;38(7):2355–67.
  48. Commune KI, Jaikumar S. Anticonvulsant herb Ipomoea reniformis—a novel approach in the screening of natural product-based anticonvulsant drug against experimentally induced convulsion in Wistar rats.
  49. Antar A, Abdel-Rehiem ES, Al-Khalaf AA, Abuelsaad AS, Abdel-Gabbar M, Shehab GM, et al. Therapeutic efficacy of Lavandula dentata oil and ethanol extract in regulation of neuroinflammation, histopathological alterations, oxidative stress, and restoring balance of Treg cells expressing FoxP3+ in a rat model of epilepsy. Pharmaceuticals. 2024;18(1):35.
  50. Thakare CV, Upasani CD. Madhuca longifolia water extract revealed protective effect against MES, PTZ and Li-pilocarpine induced epilepsy.
  51. Mohanty I, Patri M. Neuroprotective efficacy of Marsilea quadrifolia leaf extract against pentylenetetrazole-model in rat model of epilepsy. Psychol Neurosci. 2024 Sep;17(3):143.
  52. Kazemi M, Ardjmand A, Shahaboddin ME, Mehrand M, Banitaba-Bidgolia SM, Ghavipanjeh G. Effects of hydroalcoholic extract of Matricaria recutita L. on lipid peroxidation and nitric oxide in pentylenetetrazole-kindled mice. Iran J Pharm Sci. 2021;17(2):37–50.
  53. Akinpelu LA, Akanmu MA, Obuotor EM. Mechanism of anticonvulsant effects of ethanol leaf extract and fractions of Milicia excelsa (Moraceae) in mice. J Pharm Res Int. 2018;23(4):1.
  54. Mansuri S, Alex T, Chaudhary S. Comparative study of phenytoin sodium and ethanolic extract of Nardostachys jatamansi augmented with phenytoin sodium to evaluate anti-epileptic activity of the drug. J Drug Deliv Ther. 2017;7(7):218–9.
  55. Rajput MA, Khan RA, Assad T. Anti-epileptic activity of Nelumbo nucifera fruit. Metab Brain Dis. 2017 Dec;32:1883–7.
  56. Batista FL, de Araújo SM, de Sousa DB, Sobrinho FB, de Lima Silva MG, de Oliveira MR, et al. Anticonvulsant and anxiolytic-like potential of the essential oil from Ocimum basilicum Linn leaves and its major constituent estragole on adult zebrafish (Danio rerio). Neurochem Int. 2024 Sep 1;178:105796.
  57. Gupta M, Singh A, Singh S, Sagar BP. Pharmacological evaluation and comparison of anti-epileptic activity of Ocimum basilicum Linn and Ocimum sanctum Linn in albino rats.
  58. Kandeda AK, Moto FC, Ayissi RE, Omam JP, Ojong L, Bum EN. Pergularia daemia hydro-ethanolic extract protects against pentylenetetrazole kindling-model, oxidative stress, and neuroinflammation in mice. J Ethnopharmacol. 2021 Oct 28;279:114338.
  59. Tao Z, Chun-Yan H, Hua P, Bin-Bin Y, Xiaoping T. Phyllathin from Phyllanthus amarus ameliorates epileptic convulsion and kindling-associated post-ictal depression in mice via inhibition of NF-κB/TLR-4 pathway. Dose Response. 2020 Jul 31;18(3):1559325820946914.
  60. Adongo DW, Mante PK, Kukuia KK, Biney RP, Boakye-Gyasi E, Benneh CK, et al. Anticonvulsant activity of Pseudospondias microcarpa (A. Rich) Engl. hydroethanolic leaf extract in mice: the role of excitatory/inhibitory neurotransmission and nitric oxide pathway. J Ethnopharmacol. 2017 Jul 12;206:78–91.
  61. Dhakal K, Chaudhary K, Paudel S, Pant M, Adhikari C, Raj R, et al. Assessment of antioxidant, anti-epileptic and anti-anxiety activities of pomegranate leaf (Punica granatum) in mice. Asian J Pharm Pharmacol. 2021;7(2):58–62.
  62. Rahbardar MG, Hosseinzadeh H. Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders. Iran J Basic Med Sci. 2020 Sep;23(9):1100.
  63. Waqar H, Khan HM, Anjum AA. Antiepileptic potential of Silybum marianum seeds in pentylenetetrazol-induced kindled mice. Bangladesh J Pharmacol. 2016 Jun 12;11(3):603–9.
  64. Kumar R, Arora R, Agarwal A, Gupta YK. Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats. J Ethnopharmacol. 2018 Apr 6;215:124–31.
  65. Shao H, Yang Y, Mi Z, Zhu GX, Qi AP, Ji WG, et al. Anticonvulsant effect of rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy. Neuroscience. 2016 Nov 19;337:355–69.
  66. Alshabi AM, Shaikh IA, Asdaq SM. The antiepileptic potential of Vateria indica Linn in experimental animal models: effect on brain GABA levels and molecular mechanisms. Saudi J Biol Sci. 2022 May 1;29(5):3600–9.
  67. Rahimi VB, Askari VR, Hosseini M, Yousefsani BS, Sadeghnia HR. Anticonvulsant activity of Viola tricolor against seizures induced by pentylenetetrazol and maximal electroshock in mice. Iran J Med Sci. 2019 May;44(3):220.
  68. Kumar R, Bais S. Anti-epileptic activity of casticin phytoconstituent from Vitex negundo on validated animal model. J Drug Deliv Ther. 2024 Dec 1;14(12).
  69. Khattak ZF, Ansari B, Jamal M, Awan AA, Sherkheli MA, ul Haq R. Anticonvulsant activity of methanolic extract of Withania coagulans in mice. Metab Brain Dis. 2021 Dec;36:2437–43.

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Nethravathi N
Corresponding author

Department of pharmacology, Al-Ameen College of Pharmacy, Bengaluru 560027

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Dr. Rupesh Kumar M
Co-author

Department of pharmacology, Al-Ameen College of Pharmacy, Bengaluru 560027

Photo
Manjunath C
Co-author

Department of pharmacology, Al-Ameen College of Pharmacy, Bengaluru 560027

Nethravathi N, Dr. Rupesh Kumar M, Manjunath C, Ethnopharmacological Approaches to Epilepsy: Mechanisms and Preclinical Evaluation of Traditional Medicinal Plants, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 9, 2643-2656. https://doi.org/10.5281/zenodo.17182931

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