world journal of pharmaceutical research shah et al. sjif

Shah et al. World Journal of Pharmaceutical Research

www.wjpr.net Vol 9, Issue 7, 2020.

2680

HERBAL MEDICINES USED IN EPILEPSY: AN OVERVIEW

AND EFFECT OF COVID-19 ON EPILEPTIC PATIENTS

Megha S. Shah*, Bansode S. S., Gangarde S. B., Nandedkar M. A. and Dr. Oswal R. J.

Department of Pharmacognosy, Genba Sopanrao Moze college of Pharmacy, Wagholi, Pune-

412207, India.

ABSTRACT

From the times immemorial plants have been used by mankind for

their relieving and therapeutic abilities and still we rely on their

healing properties. Plants having active constituent have a direct

pharmacological action on our body including various organs. One

such major organ is brain, so complex that still only few drugs are

approved by drug authorities for ailments like epilepsy. The term

epilepsy is collectively designated for a group of chronic central

nervous system disorders characterized by spontaneous occurrence of

seizures generally associated with the loss of consciousness and body

movements (convulsions). More than 70 million people suffer epilepsy

worldwide. Low availability of anti-epileptic drugs, side effects and

drug-resistant epilepsy affect the quality of life of persons with epilepsy in countries with a

poorly developed health system. Herbal medicine is frequently used for this neurological

condition. The use of complementary and alternative medicine (CAM) is on the rise, among

patients with epilepsy. Herbal medicine, one of the most popular forms of CAM, is

considered to be both safe and effective by most consumers. There are number of synthetic

drugs available for treatment of epilepsy in modern therapy, but the major disadvantage being

faced is their chronic side effects. Treatment of epilepsy with herbal drugs as adjuvant seems

to be more beneficial and is gaining more popularity due to their fewer side effects. This

review focuses on the extent and patterns of use of herbal therapies by patients with epilepsy,

regulatory considerations for dietary supplements, safety issues, specific herbal therapies that

have been used and evaluated for epilepsy and a bench-to-bedside approach to herbal therapy

research for epilepsy.

World Journal of Pharmaceutical Research SJIF Impact Factor 8.084

Volume 9, Issue 7, 2680-2700. Review Article ISSN 2277– 7105

Article Received on

21 May 2020,

Revised on 11 June 2020,

Accepted on 03 July 2020,

DOI: 10.20959/wjpr20207-18030

*Corresponding Author

Megha S. Shah

Department of

Pharmacognosy, Genba

Sopanrao Moze college of

Pharmacy, Wagholi, Pune-

412207, India.



2681

KEYWORDS: Herbs, Epilepsy, Complementary and alternative medicine, COVID-19,

Seizures.

INTRODUCTION

The term ―epilepsy‖ is derived from Greek word ―epilambanein‖, which means ―to seize

upon‖ or ―to attack‖.[1]

Epilepsy is a condition in which a person has recurrent seizures.

Seizure can defined as an abnormal, disorderly discharging of nerve cells of brain; resulting

in a temporary disturbance of motor, sensory or mental function.[2]

Epilepsy is the most

common neurological condition affecting people of all ages, race, social class and

geographical location.[3]

Epilepsy is not curable, but can be controlled with anticonvulsant

which prevent the seizures or lessen their intensity.[4]

Though seizures can be of 2 types: epileptic seizures (ES) and psychogenic non-epileptic

seizures (PNES).It is hard to differentiate between ES and PNES with one clinical feature but

patient reported features such aslonger duration, negative emotion (particularly fear)

throughout the events, pre-seizure anxiety, ictal dissociation, and post seizure weeping.

Fewer reports of ictal self-injury and post seizure amnesia and aches may also indicate the

possibility of PNES. The presence of these features may aid diagnosis in combination with

clinical observations and/or relevant test results (e.g. video-EEG), when available. These

findings also have implications for contemporary accounts of PNES, supporting the proposal

that, in at least some instances, PNES represent a dissociative response to unpleasant or

intolerable negative emotion or autonomic arousal.[5]

Complementary and alternative medicines (CAM) are defined by the National Center for

Complementary and Integrative Health (NCCIH) of the United States National Institutes of

Health (NIH) as healthcare approaches that are developed outside of conventional medicine

for specific conditions. The common forms of CAMs reported to be used for epilepsy include

herbs, aromatherapy, vitamins, and reflexology.[6]

Complementary and alternative medicines,

like vitamins and herbal products, are generally regarded to be natural and thus safe for use.

However, there are reports of adverse effects due to CAMs, such as ginkgo and ginseng,

which triggered seizures in patients with epilepsy.[6]

Types of Epilepsy

Seizure can be differentiated in focal and generalized seizure epilepsy.[7]



2682

(a) Generalized seizures

(i) Convulsive (bilateral motor manifestations with or without loss of consciousness;

―Grandmal‖seizures)

• Tonic clonic

• Tonic

• Clonic

• Myoclonic.

(ii) Nonconvulsive (usually no motor component; consciousness impaired; ―Petitmal‖ or

absence seizures).

(b) Partial seizures

(i) Simple partial (usually unilateral focal motor signs with no loss of consciousness;

―Focalmotor‖seizures.

(ii)Complex partial (usually psychic symptoms with unusual behaviour stereotypes; usually

impaired consciousness; ―Psychomotor‖ seizures).

(iii)Partial seizures with secondary generalization (can occur with either simple partial or

complex partial seizures).[8]

HERBAL TREATMENT IN EPILEPSY

From so many years, people use variety of herbs and botanicals for the treatment of epilepsy

simply termed as Herbal Therapies. Now-a-days herbal medicines are used under the

complementary and alternative medicine (CAM) by patients. Patients with a variety chronic

illnesses, including epilepsy, take herbal therapies for many reasons. For example, patients in

developed countries may view herbal therapies as natural and time-tested and therefore safe

compared with what are perceived as artificial drugs—an attitude supported by recent reports

of safety concerns associated with widely prescribed FDA-approved drugs. In developing

countries, there may be access to herbal therapies but not to pharmaceuticals, because of

cultural and economic factors.[9]

Nardostachys jatamansi (Jatamansi)

The roots and the rhizomes of N. jatamansi DC. (Valerianaceae) mentioned in Ayurveda

have been used to treat epilepsy, hysteria, syncope, and mental weakness. Ethanol extract of

the roots was studied for its anticonvulsant activity and neurotoxicity, alone and in

combination with phenytoin in rats. The results demonstrated a significant increase in the



2683

seizure threshold by Nardostachys jatamansi root extract against maximal electroshock

seizure (MES) model as indicated by a decrease in the extension/flexion (E/F) ratio. Root

extract also showed minimal neurotoxicity against rotarod test at doses that increased the

seizure threshold. It resulted in a significant increase in the protective index (PI) of phenytoin

from 3.63 to 13.18. The dose response studies of phenytoin alone and in combination with

Nardostachys jatamansi extract on the serum levels of phenytoin clearly demonstrated the

synergistic action of both the drugs.[10]

JATAMANSI COTYLEDON ORBICULATA

Cotyledon orbiculata (seredile, plakkie, imphewula)

The anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) leaf was investigated

by studying the effects of both aqueous and methanol extracts of the plant species on seizures

induced by pentylenetetrazole (PTZ), bicuculline, picrotoxin and N-methyl-dl-aspartic

(NMDLA) in mice. Aqueous extract and methanol extract significantly prolonged the onset

of tonic seizures induced by pentylenetetrazole. Methanol extract also significantly reduced

the incidence of the seizures. Both extract of Cotyledon orbiculata significantly delayed the

onset of the tonic seizures induced by bicuculline, picrotoxin and NMDLA. Methanol extract

significantly reduced the incidence of the seizures induced by Phenobarbitone and diazepam

effectively. Studied suggested that anticonvulsant property may probably be affecting both

gabaergic and glutaminergic mechanisms to exert its effect. The phytochemical analysis

carried out revealed the presence of cardiac glycosides, saponins, tannins, reducing sugar and

triterpene steroids in the plant extract.[11]

Bacopa monnieri (Bramhi)

B. monnieri, an Indian herbal drug, reputed nootropic plant. Commonly used to treat asthma,

epilepsy, insanity and hoarseness. It is a major constituent of medhyarasayana formulations.



2684

It was evaluated alone and in combination with phenytoin for its effect on (a) passive-

avoidance (PA) task; (b) maximal electroshock seizures; and (c) locomotor activity in mice.

Phenytoin adversely affected cognitive function in the PA task. BM extract, given along with

phenytoin in the second week of the two-week regimen, significantly reversed PHT-induced

impairment. Both acquisition and retention of memory showed improvement without

affecting its anticonvulsant activity. The observed cognitive effects of PHT and BM were

found to be independent of motor stimulation. The results provide evidence for potential

corrective effect of BM in cognitive deficit associated with PHT therapy.[12]

Bacopa monnieri

and Bacoside-A treatment prevents the occurrence of seizures there by reducing the

impairment on peripheral nervous system.[13]

BRAHMI HIMALAYAN YEW

Taxus wallichiana Zucc (Himalayan Yew)

Taxus wallichiana Zucc (Himalayan Yew) is a common native herbal medicine used in the

northern areas of Pakistan and Nepal for epilepsy, is well-known for the famous anticancer

agent. Leaves of the plant are used to make herbal tea for indigestion and epilepsy.

Anticonvulsant effect of compared with that produced by the GABAA agonist diazepam, a

potent antiepileptic drug, highly effective to prevent convulsions induced by PTZ. It was

found that the methanol extracts of T. wallichiana possess potent anticonvulsant activities.

The plant extract controlled the pentylenetetrazol-induced convulsions in mice. The plant

extract, when administered, significantly inhibited myoclonus and clonus, while inhibition of

tonus and hind limb tonic extension were found to be more significant.[14]

Skullcap (scutellaria)

Wogonin is a natural product isolated from Scutellaria baicalensis, which possesses central

nervous system effects such as anxiolytic and neuroprotective activities. In this study, we



2685

investigated the effects of wogonin on convulsion related behaviors, such as myorelaxation,

motor coordination, and anticonvulsant effects of wogonin on chemical induced seizure and

electroshock seizure in mice or rats. The effect of wogonin on membrane potential was also

observed. Wogonin was intraperitoneally injected into mice or rats 30 min prior to testing.

Animals treated with wogonin did not change locomotor activities as well as endurance times

on the rota-rod, which indicates that wogonin did not cause a sedative and myorelaxation

effect. Wogonin significantly blocked convulsion induced by pentylenetetrazole and

electroshock but not convulsion induced by strychnine. Wogonin also significantly reduced

the electrogenic response score, but flumazenil treatment reversed this decrease to the level of

the control group. The wogonin treatment increased Cl-influx into the intracellular area as

dose increased. Flumazenil and bicuculline treatment, however, inhibited the Cl- influx

induced by wogonin. These results indicate that the anticonvulsive effects produced by

wogonin were mediated by the GABAergic neuron.[15]

American skullcap (the aerial part

of Scutellaria lateriflora L.) has been traditionally used by Native Americans and Europeans

as a nerve tonic, sedative, and anticonvulsant. Twelve phenolic compounds including

10 flavonoids and two phenylethanoid glycosides were isolated and identified from American

skullcap and used as marker compounds. The anticonvulsant activity of American skullcap

was determined in rat models of acute seizures induced by pilocarpine and

pentylenetetrazol.[16]

Twenty-six flavonoids were isolated from Scutellaria baicalensis. Their

affinities for the benzodiazepine (BDZ) binding site of GABA A receptor have been studied

using [3H] flunitrazepam binding to rat cortical membranes in vitro. The structure-activity

relationships suggested that 2'-OH flavones exhibited the most potent binding affinity, which

could lead to the design and discovery of new BDZ receptor ligands.[17]

SKULLCAP JUJUBE

Zizyphus jujube

https://www.sciencedirect.com/topics/medicine-and-dentistry/scutellaria-lateriflora

https://www.sciencedirect.com/topics/medicine-and-dentistry/anticonvulsant

https://www.sciencedirect.com/topics/medicine-and-dentistry/phenol-derivative

https://www.sciencedirect.com/topics/medicine-and-dentistry/flavonoid

https://www.sciencedirect.com/topics/medicine-and-dentistry/glycoside

https://www.sciencedirect.com/topics/medicine-and-dentistry/pilocarpine

https://www.sciencedirect.com/topics/medicine-and-dentistry/pentylenetetrazol



2686

The anticonvulsant effect of the hydroalcoholic extract of Zizyphus jujuba (HEZJ) fruit was

evaluated in experimental seizure models in rats. The effect of HEZJ on seizure-induced

cognitive impairment, oxidative stress, and cholinesterase activity was also investigated.

HEZJ (1000 mg/kg) exhibited maximum protection (100%) against generalized tonic-clonic

seizures in the pentylenetetrazole (PTZ) seizure model and and 66.7% protection against

tonic hind limb extension in the maximal electroshock (MES) seizure model. Significant

impairment in cognitive functions was observed in both PTZ- and MES-challenged rats.

Pretreatment with HEZJ resulted in significant improvement in learning and memory. HEZJ

also reversed the oxidative stress induced by both PTZ and MES. The significant decrease in

cholinesterase activity observed in the PTZ and MES models was significantly reversed by

pretreatment with HEZJ. Thus, the present study demonstrates the anticonvulsant effect of

HEZJ as well as amelioration of cognitive impairment induced by seizures in rats.[18, 19]

Uncaria rhynchophylla(Cats Claw)

Uncaria rhynchophylla is another common herbal medicine in traditional Chinese medicine

used for epilepsy. The antiepileptic effects have been seen in kainic acid-induced epileptic

seizures models.[20–22]

There are several compounds found in Uncaria rhynchophylla and the

neuroprotective related compounds of those are rhynchophylline and

isorhynchophylline.[23, 24]

Studies indicated that the anticonvulsant effects on kainic acid-

induced epileptic seizures may be medicated by the regulation of immune response and

neurotrophin signaling pathway and inhibition of gene expression: neuron survival brain-

derived neurotrophin factor (BDNF) gene and inflammation gene IL-1β.[25]

GINSENG CATS CLAW HERB

Ginseng

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564656/#R32



2687

Ginseng is one of the most common herbal medicines used for ailments in China, Korea and

America. Some studies have shown that ginsenosides play a significant role in most

pharmacological effects of ginseng, including anti-inflammatory and neuroprotective effects.

Both single and chronic administration of ginseng extracts can reduce the development of

neurodegeneration, inflammation and larger permeability caused by status epilepticus

particularly in the hippocampus at the initial days, but cannot completely reverse the

reduction of hippocampal volumes in rats for a month after status epilepticus. Chronic

administration of ginseng extract on rats exhibited no toxic effects, but high dose more than

150 mg/kg treatment on rats increased mortality rate after status epilepticus induced by

pilocarpine. It is reported that Korean red ginseng extracts also significantly increase the

electrical seizure threshold in rat offspring. Some studies on the neuroprotective mechanisms

of ginsenosides indicate that ginsenosides inhibit NMDA-dependent and status epilepticus

induced Ca2+

influx, and L-type Ca2+

channels in hippocampal neurons.[26-28]

Passiflora incarnata (purple passion flower)

The aerial parts of Passiflora incarnata contain multiple bioactive metabolites such as,

flavonoids (like, chrysin that show CNS depressant activity by agonizing GABA-

benzodiazepine receptor), amino acids (like, GABA), harmala alkaloids (reversible

monoamine oxidase-A inhibitor), etc. It was investigated that passifloraincarnatahas dual

protective effect in PTZ induced seizures and dissociated post-ictal depression. Treatment

with the extract significantly reduced the seizure severity and immobility period as compared

to vehicle control, in a dose and time-dependent manner. Moreover, the extract treatment

retained the serotonin and noradrenaline levels of the brain. The results of present study

concluded that the hydroethanolic extract suppress PTZ-induced seizures, and ameliorates its

associated post-ictal depression, which has been found to be get worsened with the standard

antiepileptic drug, diazepam.[29]



2688

PURPLE PASSION FLOWER ASHWAGANDHA

Withania somnifera (Ashwagandha)

the effect of Withaniasomnifera (WS) extract, withanolide A (WA), and carbamazepine

(CBZ) on cerebellar AMPA(alpha-amino3-hydroxy-5-methylisoxazole-4-propionic acid)

receptor function in pilocarpine-induced temporal lobe epilepsy (TLE). In the present study,

motor learning deficit was studied by rotarod test, grid walk test, and narrow beam test.

Motor learning was significantly impaired in rats with epilepsy. The treatment with WS and

WA significantly reversed the motor learning deficit in rats with epilepsy when compared

with control rats. There was an increase in glutamate content and IP3 content observed in rats

with epilepsy which was reversed in WS- and WA-treated rats with epilepsy.[30]

Terminalia Chebula (Hirda)

The anticonvulsant activity of ethanolic extract of fruits of Terminalia chebula in mice was

assessed by using maximum electroshock seizure (MES) test, Pentylenetetrazole (PTZ), and

picrotoxin (PC) test. The ethanolic extract of Terminalia chebula (EETC) possess

anticonvulsant activity since it reduced the duration of seizures produced by maximal

electroshock and delayed the latency of seizures produced by pentylenetetrazole (PTZ) and

picrotoxin.[31]

https://www.sciencedirect.com/topics/medicine-and-dentistry/glutamic-acid



2689

HIRDA VISCUM ALBUM

Viscum album (Loranthaceae)

The aqueous leaf extract of Viscum album L. reduced locomotor activity facilitate

GABAergic transmission. In addition the extract reduced MES, INH and PTZ-induced

convulsions which suggest that there may be possibility of blocking Na+ channels, opening of

Cl−channels or enhancing the GABAergic system.

[32]

PLANTS USED IN THE TREATMENT OF EPILEPSY[33]

Plant Family Part used Uses

Abrus precatorius L. Leguminosae Leaves Anticonvulsant

Abrusprecatorius Linn. Fabaceae Roots, leaves

Love and good luck charms, pleuritic

chest complaints, eye ailments,

contraception, convulsions

Acacia karroo Hayne Fabaceae Stem-bark,

leaves, gum

Colds, oral thrush, stomach ache,

osteomyelitis, dizziness, convulsions

Acorus calamus Araceae Rhizome

Insomnia, melancholia, neurosis,

epilepsy, antioxidant activity,

antistressor activity

Blumea alata Asteraceae Roots, leaves Fevers, convulsions, constipation,

colic and abdominal pains

Boscia albitrunca Capparaceae Roots, leaves,

fruits

Hemorrhoids, inflamed eyes,

epilepsy

Calliandra portoricensis Mimosaceae Roots and stem Gastrointestinal tract (GIT) problems

and convulsions

Capparis tomentosa Lam. Capparaceae Roots, leaves Asthma, constipation, eye problems,

convulsions

Casimiroa edulis Rutaceae Leaves Sedative, antiepileptic

Catunaregam spinosa Rubiaceae Roots, leaves,

fruits

Epilepsy and dizziness, fevers,

aphrodisiac, headaches snakebite,

nausea

Cestrum nocturnum Solanaceae Leaves Antiepileptic

Clausena anisata (Willd.)

Hook. F. ex Benth Rutaceae

Roots, leaves,

fruits

Convulsions, teniasis and other

parasitic infections, constipation,

rheumatism, malaria and fevers



2690

Clerodendrum glabrum E.

Mey Verbenaceae Leaves, roots

Fevers, intestinal parasites,

childhood convulsions, colds

Commelina Africana Linn. Commelinaceae Roots Insomnia, infertility, epileptic ‗fits‘,

heart complaints

Conyza scabrida DC. Asteraceae Leaves, roots Convulsions, colds and coughs,

pleuritic pains

Crassula alba Forssk. Crassulaceae Leaves, twigs Epilepsy, dysentery and diarrhea,

bloody stools

Croton gratissimus Burch. Euphorbiaceae

Stem-

bark/roots/leav

es

Edema (dropsy), coughs,

inflammation, insomnia, aphrodisiac,

epilepsy

Cucumis hirsutus Sond Cucurbitaceae Roots, fruits Convulsions, abortion, penal, vulval

sores

Datura

stramonium Linn. Solanaceae

Leaves, fruits,

aerial parts

Gout, boils, abscesses and wounds,

aphrodisia, motion sickness, sore

throat and tonsilitis, visceral pains,

epilepsy and Parkinsonism

Englerophytum

magalismontanum Krause Sapotaceae Roots, fruits

Epilepsy, headaches, abdominal

pains

Euclea divinorum Hiern Ebenaceae Fruits, roots,

stem-bark

Convulsions, toothaches,

constipation, schistosomiasis, chest

pains

Flacourtia indica Willd Flacourtiaceae Sterm-barks,

fruits, leaves

Epilepsy, headache, fever, stomach-

ache, diarrhea sleep disorders

Hibiscus rosa-sinensis Malvaceae Fresh flowers Brain tonic, anticonvulsant,

aphrodisiac

Jatropha curcas Linn Euphorbiaceae Roots, seeds,

leaves

Angina, herpes, malaria, jaundice,

fevers, diarrhea, ringworm,

rheumatism, convulsions

Jatropha gossypiifolia

Linn. Euphorbiaceae Leaves, roots

Convulsions, fever, hypertension,

convulsions

Kigelia africana (Lam.)

Benth Bignoniaceae

Fruits, stem-

bark

Rheumatism, acne, pneumonia,

convulsions, aphrodisia, hemorrhoids

Lannea discolor Anacardiaceae Leaves, stem-

bark, roots

Convulsions and ‗fits‘, diarrhea,

abscesses and boils, infertility,

menorrhagia

Lippia javanica (Burm. F.)

Sreng. Verbenaceae Leaves, twigs

Coughs, colds, bronchitis, asthma

and other chest ailments, malaria,

fevers, stomach problems and

headaches, convulsions, cataracts

Maytenus senegalensis Celastraceae Roots, leaves

Hemoptysis, respiratory ailments,

epilepsy, body pains, constipation,

diarrhea

Melia azedarach Linn. Meliaceae

Leaves, root-

bark,

heartwood

Abdominal pains, helmintiasis,

epilepsy, fits/ convulsions,

schistosomiasis, swollen legs

Mimosa pudica Linn. Fabaceae Whole plant Convulsions/epilepsy,

dysmenorrhea, heart palpitations

Ranunculaceae Analgesic and central nervous



2691

Nigella sativa Seed extract system (CNS) depressant,

antibacterial, antihistaminic, petit,

mal epilepsy

Nuxia floribunda Benth. Loganiaceae Leaves/stem-

bark

Fevers, coughs, indigestion,

influenza, infantile convulsions

Oxygonum

dregeanumMeisn. Polygonaceae Roots, leaves

Abdominal pains, inflammatory

conditions, schistosomiasis,

convulsions, whooping cough

Phytolacca dodecandra L.

Herit. Phytolaccaceae

Roots, leaves,

berries

Urinary complaints, snakebite,

epilepsy, uterine tumors

Pimpinella anisum Umbelliferae Essential oil

from fruits

Anticonvulsant activity, muscle

relaxant, hypothermic

Rauvolfia caffra Apocynaceae

Stem-bark,

root-bark,

leaves

Mental problems, insomnia and

hysteria, rashes, convulsions, asthma

Rhoicissustridentata (Linn.

F.) Wild and Drum. Vitaceae

Roots, tubers,

leaves

Epilepsy, dysmenorrhea, safe

delivery in pregnancy, renal

complaints

Rubus pinnatus Willd. Rosaceae Roots, leaves

Toothaches, convulsions, chronic

diarrhea, abdominal cramps,

rheumatism

Senna singueana Caesalpiniaceae

Leaves,

flowers, barks,

roots

Fever, conjunctivitis, convulsions,

gonorrhea, bilharzias, stomach-aches

Tecomaria capensis

(Thunb.) Spach Bignoniaceae

Stem-bark,

leaves

bacterial infections, stomach pains,

influenza, pneumonia, convulsions

Terminalia mollis Laws Combretaceae Roots Epilepsy

Trichilia emetic Vahl Meliaceae Roots, barks Epilepsy, anti-parasitic diseases,

head aches

Vernonia neocorymbosa

Hilliard Asteraceae

Leaves, twigs,

root

Epilepsy, abortion, stomach ache,

hysteria, irregular menstruation

Viscum capense Loranthaceae Stem Antiepileptic, asthma, irregular

menstruation

Vitelaria paradoxa Sapotaceae Leaves, barks Convulsions, epilepsy, headaches,

stress, head aches

Vitexa gnus-castus Lamiaceae Fruit, leaves Epilepsy, psychoactive

The anticonvulsive and antiepileptic mechanism of herbal medicine[26]

Herbal

Medicine Region

Cells/Animals/

Humans Seizure Model Action Target Mechanism

Apocynaceae Africa

In vitro model

(cerebral cortex

from rats)

- GABAA

receptor

Enhances GABA‘s

affinity to the GABAA-

receptor.

Bryonia alba Iran

In vitro model

(cerebral cortex

from rats)

-

Benzodiazepin

e site on the

GABAA

receptor

Enhances the receptor

sensitivity for

endogenous GABA

Caesalpinia

bonducell Iran

Animal

model(mice)

MES

Pentylenetetrazol

Chloride ion

channel linked

Blocks chloride ion

channel linked to GABA



2692

Picrotoxin to GABA

receptors

receptors

Cannabis

Asia,

Europe

and so on

In vivo and in

vitro models

Pentylenetetrazol

Pilocarpine

cannabinoid

receptor type 1

Promotes cannabinoid

receptor type 1

expression and

localization on different

presynapses (i.e.

excitatory or inhibitory)

GABAergic

circuits

Inhibits GABAergic

circuits in brain areas

crucial to epileptogenesis

Diacylglycerol

lipase α

Inhibits diacylglycerol

lipase α, which is the

enzyme responsible for

the production of the

endocannabinoid 2-

arachidonoylglycerol, to

increase the number of

cannabinoid receptor type

1 at the membrane.

Compound

herbal medicine China Humans

- NMDA

receptors

Prolong the attenuation

duration of NMDA

receptor channels and

alter the expression of

NMDA receptor subunits

Calcium

channel

Reducing in the

concentration of

intraneuronal Ca2+

inside

the hippocampal neurons

Euphorbiaceae Africa

In vitro model

(cerebral cortex

from rats)

- GABAA

receptor

Enhances GABA‘s


receptor

Ficusplatyphyll

a Nigeria

Animal

model(mice)

Pentylenetetrazol Calcium

channel

Inhibition of T-type Ca2+

currents

Aminophylline NMDA

receptor

Blocks glutamatergic

neurotransmission

mediated by the NMDA

receptor

Isonicotinic

hydrazide acid GABAergic Affinity for GABAergic

Picrotoxin Glycine

Interference with

postsynaptic inhibition

mediated by glycine, an

important inhibitory

transmitter to motor

neurons and interneurons

in the spinal cord

Strychnine Free radicals

Scavenging action of free

radicals (such as reactive

oxygen and nitrogen



2693

species)

Glutamatergic

receptors

Affinity for glutamatergic

receptors, and reduction

of glutamate release

Ganoderma

lucidum China

In vivo and in

vitro models - Neurotrophin-4

Promotes NT-4

expression, NT-4 can

promote neuron survival,

alleviate neuronal

injuries, inhibit neurons

from apoptosis and adjust

the synapses plasticity

N-Cadherin

Indirectly inhibits mossy

fibres sprouting and

adjust the synaptic

reconstructions by

inhibiting the expression

of N-Cadherin

Epileptic

hippocampus

Ca2+

concentration

Inhibits calcium overload

to prevent an epileptic

episode induced by Mg2+

deficiency

CaMK IIα

expression

Promotes the expression

of CaMK IIα to prevent

the onset of epilepsy

Ginseng America,

China

Animal

model(rats) MES

Ca2+

influx and

channels

Inhibits NMDA-

dependent and status

epilepticus induced Ca2+

influx, and L-type Ca2+

channels in hippocampal

neurons

Gladiolus

dalenii

Africa Animal

model(mice) MES

GABAA

receptor

Interacts with the

GABAA neuro-

transmission specifically

through the

benzodiazepine site

receptor. Increase of the

GABA brain content

Pentylenetetrazol Sodium

channel

Prolongs the inactivation

of sodium channel

Lamiaceae Africa

In vitro model

(cerebral cortex

from rats)

- GABAA

receptor

Enhances GABA‘s


receptor

Lavandula

officinalis Iran

Animal model

(male mice)

Pentylenetetrazol Glutamate

release

Prevents glutamate

induced neurotoxicity of

cerebellar granular cell

culture of rat pups

GABA

receptors

Enhance of GABA

receptors

Calcium

channel Block calcium channel



2694

Lavandula

stoechas Iran

Animal

model(mice) Pentylenetetrazol

Calcium

channel Blocks calcium channel

Passiflora

invarnate

America

and

Europe

In vivo and in

vitro models Pentylenetetrazol GABA

Passiflora extracts

contain a large amount of

GABA, and can induce

direct GABAA currents in

cornuammonis 1

hippocampal pyramidal

neurons

Pimpinella

anisum

Asia and

so on

In vivo and in

vitro models Pentylenetetrazol

Na+-K

+

ATPase and

GABAA

receptors

Enhances the activity of

the Na+-K

+ ATPase,

which inhibits both

GABAA and GABAB

components of inhibitory

postsynaptic potentials

Salvia

miltiorrhiza China

Animal model

(Zebra fish and

Mouse)

Pentylenetetrazol

GABA and

related

Agonists

A propensity to interact

with pathways irrelevant

to GABA and related

agonists

Skullcap

America,

Europe

and China

Animal model

(rats) Pentylenetetrazol

GABAA

receptor

High affinity to GABAA

receptor

Neuroprotectiv

-e effects

Neuroprotective effects

mediated by anti-

oxidation,

antiinflammation, and

anti-excitotoxicity

Uncariarhynch

ophylla

China Animal

model(rats) Kainic acid

Pathways in

both cortex and

hippocampus

regions

Exhibit anti-convulsive

effects by regulating

immune response and

neurotrophin signaling

pathway

Gene

expression

Ameliorate kainic acid

induced seizures by

regulating the expression

of genes involved in

neuron survival and

inflammation

Viscum album Asia and

Europe

Animal model

(mice and rats)

Pentylenetetrazol

MES,

Isonicotinic

hydrazide acid

GABA

Enhances the response to

GABA, by facilitating the

opening of GABA-

activated chloride

channels

Zingiber

officinale

China and

India

Animal

model(rats)

Pentylenetetrazol NO and iNOS

Inhibits NO production

and reduces iNOS in

lipopolysaccharide-

stimulated mouse

macrophages

NO/cGMP

Pathway

Elevated intracellular

cGMP level



2695

Chloride ion

channel in the

complex of

GABAA

receptors

Inhibits Chloride ion

channel in the complex of

GABAA receptors

Calcium

channel Block calcium channel

Zizyphus jujube India Animal

model(rats)

Pentylenetetrazol Voltage-gated

Channel

Prolongs Na+ channel

inactivation

MES GABA channel Inhibits effect of GABA

and reduce the excitation

Glutamate and

NMDA

Inhibits glutamate-

induced over excitation,

reduces synaptic release

of glutamate or NMDA

Antioxidant

effect

Reverses antioxidant–

oxidant imbalance by

decreasing NMDA levels

and increasing

glutathione levels

MARKETED FORMULATIONS AVAILABLE IN INDIA FOR EPILEPSY[33]

Product/dose Manufacturer Price (INR) Formulation

Asvagandhadyarishta (20-40 ml) Zandu Pharmaceuticals Works

Ltd 80 Liquid

Bali tail Sandu Pharmaceuticals Limited - Oil

Brahmighruta (12 mg) Shree BaidynathAyurvedPvt. Ltd 216 Tablet

Chandanadi tail Arya Vaidya Pharmacy 414 Oil

Chaturmukha rasa (125-250 mg) Dabur India Ltd. 77 Tablet

Haratalabhasma (1/4-1/2 ratti) Divya Pharmacy 31.25 Powder

Kalyanakaghruta (125 mg) NagarjunaAyurvedic Group 71.90 Tablet

Kumaryasava (125 mg) Dabur India Ltd. 82 Tablet

Mahakalayanakaghruta (125 mg) NagarjunaAyurvedic Group 98.95 Tablet

Mahamrutyunjaya rasa (125-250 mg) Uma Ayurvedics Pvt Ltd 98.95 Tablet

Rajatabhasma (1/2 ratti) Divya Pharmacy - Powder

Saarasvatarishta (20-40 ml) Uma Ayurvedics Pvt Ltd - Tablet

Sarpagandhavati (125 mg) Dabur India Ltd 80 Powder

Svarnabhasma (1/8-1/4 ratti) Shree Dhootapapeswar Ltd 67.95 Liquid

Svarnamakshikabhasma (102 rtti) Divya Pharmacy 1,030 Powder

Vaatakulantaka rasa (125-250 mg) Dabur India Ltd 78 Tablet

Yogendra rasa (125 mg) Dabur India Ltd 79 Tablet

INR: Indian rupee

Effect of COVID-19 on epileptic patients

The Centre for Disease Control and Prevention (CDC) suggests that neurological

comorbidities, including epilepsy, may be a risk factor for COVID-19, despite the lack of

evidence. Presently, a medical history of epilepsy has not been reported to be a risk factor for



2696

developing COVID-19. Certain pre-existing conditions (such as smoking, obesity, diabetes,

heart disease, lung disease, and cancer) are recognized as risk factors. Therefore, patients

with epilepsy with these comorbidities may adopt a more cautionary approach regarding

COVID-19. Conversely, children infected with COVID-19, including those just with

wellcontrolled epilepsy and no other health conditions, are generally asymptomatic or present

with mild symptoms. According to previous data, the rate of neurological comorbidity has

not been assumed to be greater for COVID-19 than other respiratory viral infectious diseases.

Conversely, patients with epilepsy infected with COVID-19 or any other infectious diseases

may have fever, which may possibly trigger seizures. Certain epilepsy medications may

affect the immune system, including everolimus and steroids that are used for tuberous

sclerosis complex and autoimmune epilepsy, respectively. Some societies do not recommend

changing the AEDs of patients with well controlled seizures, as seizure exacerbations or

status epilepticus may increase the risk of COVID-19 infections.

Some societies suggest that COVID-19 could increase the risk of sudden unexpected death in

epilepsy (SUDEP). There are some reports that indicate that infection or viral infectious

disease might increase the risk of SUDEP. However, there are still no data on the association

between COVID-19 and SUDEP.[34]

The Coronavirus disease 2019 (COVID-19) pandemic has created a huge surge in demand for

intensive care resources in a short time frame, overwhelming some national and sub -regional

health systems, and resulting in the need for resource rationing. Coronavirus disease 2019 is

likely have major implications on the management of status epilepticus (SE) in the intensive

care unit (ICU) because of potential limits in ventilator and staff capacity. In treating SE,

there is a challenge for need of ICU resources and ventilators in the era of the COVID-19

pandemic. The optimal approach will be to follow management pathways that avoid sedation

if possible and taking into consideration ASD-antiviral medication interactions. Coordinated

multidisciplinary efforts are required that will use creative solutions, non-sedating ASDs, and

risk–benefit calculations when embarking on emergency SE management in this resource-

constrained time.[35]



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