Evidence-Based Complementary and Alternative Medicine / 2019 / Article / Tab 1

Review Article

The Effects of Various Essential Oils on Epilepsy and Acute Seizure: A Systematic Review

Table 1

Essential oils with anticonvulsant activity.

EO or ConstituentStudy TypeDosageEffectsReference

alpha-Asaroneanimal (mice) PTZ, MES200 mg/kgLittle effect on acute PTZ, MES model animals[18]

alpha-Asaroneanimal (rat) pilocarpine spontaneous recurrent seizures200 mg / kgChronic daily treatment at this dose for 28 days abolished all convulsions and prevented mortality in 100% of animals. 100% of control animals experienced convulsions and mortality was 40% in the controls.[18]

alpha-Asaroneanimal (mice) MES25 mg/kgProtected against MES seizures. Interacted competitively with chlorpromazine.[19]

beta-Asaroneanimal (mice) MES25 mg/kgSlightly increased susceptibility and mortality. No effect on chlorpromazine activity.[19]

Acorus gramineus rhizomeanimal (mice) PTZ30 days inhalationIncreased brain GABA levels and decreased glutamate content by inhalation of the oil. PTZ-seizure animals which inhaled the oil for 30 days had brain higher GABA levels and lower glutamate levels, close to the control animals which did not go through PTZ-induced seizures periodically. The mechanism was determined to be inhibition of the GABA transaminase enzyme.[20]

Acorus tatarinowii Schott rhizomeanimal (mice) PTZ, MES1.25 g / kg;ED50 for MES. No effect on PTZ induced seizures, but prolonged latency and decreased convulsive rate. Also decreased mortality.[21]

Angelica archangelica Linn.animal (mice) MES, PTZ400 mg/kg83% protection, 16% mortality from PTZ seizures[22]

Angelica archangelica Linn.animal (mice) MES, PTZ500 mg/kg100% protection from MES seizures, no mortality; duration reduced 20-fold, latency increased four-fold[22]

Artemisia annua L.animal (mice), PTZ, pilocarpine, PCTX, STRN470 mg/kgED50 for PTZ seizures. Increased latency to pilocarpine and PCTX-induced convulsions. Prevented onset of PTZ and STRN-induced seizures. Motor inhibition was a side effect.[23]

Artemisia dracunculus L.animal (mice) PTZ, MES model0.84 mL / kgED50 for MES animals[24]

Artemisia dracunculus L.animal (mice) PTZ, MES0.26 mL/kgED50 for PTZ animals[24]

Bunium persicumanimal (mice) PTZ, MES1 mL / kg0% of convulsive movements compared to PTZ-only control[25]

Bunium persicumanimal (mice) PTZ, MES1.25 mL / kg0% of convulsive movements compared to MES only control[25]

trans-Caryophylleneanimal (mice) kainic acid60 mg/kgReduced mortality by 50% compared to kainic acid-only group. Significantly reduced seizure activity score around two-fold. Also lessened seizure severity by inhibiting malondialdehyde synthesis and preserving activity of GPx, SOD, and CAT. Reduced levels of the inflammatory cytokines TNF-a and IL-1B.[26]

Calamintha officinalisanimal (mice) PTZ50 mg/ kg55% reduction in average duration of convulsions, latency period 21.7 times longer than controls and comparable to animals treated with 1 mg/kg diazepam.[27]

Calamintha officinalisanimal (mice) PTZ100 mg/kg75% reduction in seizure duration, latency period 22.2 times longer than controls[27]

Carum Carvi L. animal (mice) PTZ42.3 mg/kgED50 for PTZ clonic seizures[28]

Carum Carvi L.animal (mice) PTZ97.6 mg/kgED50 for PTZ tonic seizure[28]

R-Carvoneanimal (mice) PTZ, PCTX200 mg/kgno effect[29]

S-Carvoneanimal (mice) PTZ, PCTX200 mg/kgSignificantly increased latency of convulsions[29]

Cinnamosma madagascariensis Danguyanimal (rats) PTZ0.8 mL/kgPrevention of all convulsions and mortality. Some slight sedative effects were observed.[30]

Citronellolanimal (mice) PTZ, MES, PCTX400 mg / kgIncreased seizure latency by around 50% and reduced the percent of animals with convulsions by 75% in PTZ model. For MES animals, the reduction in convulsions was identical at the same dosage of 400 mg/kg, with 75% protection from tonic convulsions.[31]

CitronellolIn vitro nerve fibers6.4 mM solutionCompound action potentials reduced by 90% in nerve bundle bathed in citronellol. There was no effect on repolarization, but only the initial depolarization.[31]

Citrus aurantium blossomanimal (mice) PTZ, MES40 mg / kgIncreased the clonic seizure threshold by 50%. The EO provided 92% seizure protection and 100% survival, compared to 0% protection and 30% surivival in controls. flumazenil reversed protection, indicating the involvement of GABA-ergic system.[32]

Citrus aurantium peelanimal (mice) MES, PTZ1g/kgIncreased latency period for MES and PTZ[33]

Cuminum cyminum Linnin vitro neurons, PTZ1% v/vDecreased spontaneous activity induced by PTZ in a concentration dependent manner[34]

Curzereneanimal (mice) PTZ0.4 mg/kg100% prevention of PTZ convulsions and mortality[35]

Curzereneanimal (mice) PTZ0.25 mg/kgED50[35]

Cymbopogon citratusanimal (mice) MES, PTZ1 g/kgDelayed clonic seizures induced by PTZ and blocked tonic extensions induced by MES. Prevented 40% of tonic convulsions in PTZ animals and 80% of tonic convuslions in MES animals. No significant effect on clonic convulsions.[36]

Cymbopogon citratusanimal (mice) PTZoral dose of 200 mg/kgNo effect[37]

Cymbopogon citratus & Cymbopogon winteraniusAnimal (mice) PTZ, STRN200 mg/kgIncreased seizure latency 8-fold and also increased latency to death in both PTZ and strychinine models. Effects blocked by flumazenil and potentiated by diazepam.[38]

Cymbopogon winterianusanimal (mouse) PTZ, PCTX, phenytoin, STRN200 mg/kgSeizure latency increased nearly seven fold. Percent of animals experiencing convulsions was reduced by 50% and survival increased from 20% (control) to 70% (EO treatment group).[39]

p-Cymeneanimal (mice) MES970 mg/kgED50 for MES seizures[40]

p-Cymeneanimal (mice) PTZ393 mg/kgED50 for PTZ seizures[40]

Dehydrofukinonein vitro and animal (mice) PTZ100 mg/kgDelayed onset of generalized tonic-clonic seizures. Induced hyperpolarization of neurons via GABA activation. Decreased calcium mobilization from synapse. Activity could be reversed by flumazenil.[41]

Denettia tripetalaanimal (mice) PTZ, STRN200 mg/kg100% protection from PTZ and STRN-induced convulsions. Co-treatemnt with flumazenil, a GABA receptor antagonist, abolished the anticonvulsant effects on the EO and the constituent.[42]

Elettaria cardamomumanimal (mice) PTZ, MES1 mL/kgSignificantly delayed onset of clonic seizures, prevented all PTZ seizures and 62.5% of MES seizures at this dose. Showed some degree of movement toxicity.[43]

(-)-Epoxycarvoneanimal (mice) PTZ, pilocarpine, STRN300 mg/kgOnly 12.5% inhibition of PTZ convulsions. No effect on STRN animals. Protected against pilocarpine seizures.[44]

(+)-Epoxycarvoneanimal (mice) PTZ, pilocarpine, STRN300 mg/kgIncreased latency to PTZ-induced seizure onset with 100% survival. Prevented tonic seizures induced by MES. Exhibited 25% inhibition of PTZ convulsions. No effect on strychine animals. Protected against pilocarpine seizures.[44]

Eugenia caryophyllataanimal (mice) MES, PTZ0.1 mL/kgAbolished all convulsions in MES mice and 100% survival. Nearly doubled PTZ seizure threshold, but only reduced convulsions by 20% in mice above the threshold.[45]

Eugenolanimal (mice) pilocarpine-No difference in seizure latency, but decreased duration and intensity of pilocarpine-induced seizures about threefold each.[16]

Eugenolpatch-clamp electrophysiology-Depressed transient and late components of sodium current. It also decreased L-type calcium currents and delayed rectifier potassium currents at higher concentrations.[16]

Eugenolanimal (rats) pilocarpine100 mg/kg for 7 days55% reduction in average duration of convulsions. Latency period was 21.7 times longer than controls and comparable to animals treated with 1 mg/kg diazepam. Neuronal loss was prevented by eugenol treatment in epileptic animals in all hippocampal sub-regions including DG, CA3, and CA1. Seizure stage and mortaility were improved.[46]

Gardenia lucida resinanimal (mice) MES, PTZ300 mg/kgFor MES animals, the EO reduced convulsion time nearly tenfold and reduced recovery time six-fold. In PTZ animals, the EO increased latency fourfold and reduced number of convulsions twofold. Loss of motor function was a side effect.[47]

Hydroxydihydrocarvoneanimal (PTZ)400 mg/kgPTZ seizure latency increased two-fold. Side effects included palpebral ptosis, decreased response to touch, increased sedation. Decreased motor activity. Protected against PTZ-induced convulsions.[48]

Laurus nobilis leafanimal (mice) PTZ, MES0.75 mL/kgPrevented all convulsions in PTZ mice and 0% mortality. Also produced sedation and motor impairment at anticonvulsant doses[49]

Laurus nobilis leafanimal (mice) PTZ, MES1 mL/kgIn MES animals, prevented 80% of convulsions. Only 10% mortality. Also produced sedation and motor impairment at anticonvulsant doses.[49]

Lavandula angustifoliain vitro human embryonic kidney cells0.034 mg/mLLavender and rosemary essential oils both inhibit CaV3.2 T-type calcium channels. Linalool was determined to be the active component.[50]

Lavandula angustifoliaanimal (mice) PTZ, strychinineInhalation of 1 mLInhalation of 1 mL of lavender oil 15 minutes before treatment with 50 mg/kg PTZ prevented all convulsions in 100% of the animals and prevented mortality. All animals in the control group experienced seizures and there was a 100% mortality rate at this dose. In this experiment, lavender had no effect on STRN induced seizures.[51]

Linaloolin vitro snail neurons0.1 mMsupressed spontaneous activity and PTZ induced epileptiform activity[52]

Linaloolin vitro snail neurons0.4 mMInduced epileptiform activity. This epileptiform was reversed by calcium channel blockers.[52]

Linaloolin vitro-In vitro assays showed that linalool displaced an NMDA antagonist, MK801, which directly interacts with NMDA receptors. This suggests a direct interaction between linalool and NMDA receptors. There was no effect on muscimol binding, so no conclusive evidence was obtained about a GABAergic mechanism.[53]

Linaloolanimal (mice) MES, PTZ, STRN-Increased latency period and decreased mortality in all models[54]

Linalool oxideanimal (mice) MES, PTZ150 mg/kgModerately reduced duration of tonic seizures induced by MES and increased latency to PTZ seizures.[55]

Lippia alba, citral chemotypeanimal (mice) PTZ100 mg/kgIncreased seizure latency and percentage of survival[56]

Lippia alba, limonene chemotypeanimal (mice) PTZ200 mg/kgIncreased seizure latency and percentage of survival[56]

Lippia alba, myrcene chemotypeanimal (mice) PTZ200 mg/kgIncreased seizure latency and percentage of survival[56]

Mentha piperitaanimal (mice) PTZ1.6 mL/kgCompletely prevented all seizures at all and produced a rate of 100% survival.[57]

Mentha spicataanimal (mice) PTZ1.6 mL/kg12-fold increase in seizure latency[57]

Myristica fragransanimal (mice) MES, STRN, bicuculline, PTZ0.2 mL/kgIncreased latency to PTZ seizure and death 2-fold. 100% protection from convulsions induced by MES. Delayed onset of convuslions by STRN. At high doses, was a weak proconvulsant. No motor impariment was observed.[58]

Ocimum gratissimum L.animal (mice) MES, PTZ1g/kgAverage of about 30 percent protection from MES convulsions. Little effect on PTZ convulsions[59]

Pimpinella anisum fruitanimal (mice) MES, PTZ1 mL/kgNearly doubled the PTZ seizure threshold. Protected against 80% of convulsions and prevented death in 90% of animals for both PTZ and MES conditions.[60]

Pimpinella anisum fruitanimal (mice) PTZ3 mL / kgLatency increased five-fold with a treatment of 3 mL / kg. Inhibited production of dark neurons in different regions of brain in epileptic rats. Prolonged latency and reduced amplitude and duration of PTZ seizures.[61]

alpha-Pineneanimal (mice) PTZ440 mg/kgED50 for PTZ seizures[40]

Psidium Guyanensis leafanimal (mice) PTZ, PCTX, STRN400 mg/kgReduced severity of PTZ seizures but not strychine or picroptoxin. Caffeine reversed the effect, suggesting that the mechanism involves the adenosine system.[62]

Rosa damascenaanimal (amygdala electrical kindling)750 mg/kgNumber of stimulations necessary for first appearance of seizure was larger in animals treated with the EO. Seizure duration was shorter in the treatment groups.[63]

Rosmarinus officinalisin vitro human embryonic kidney (HEK) cells0.054 mg/mLRosemary essential oil was found to inhibit CaV3.2 T-type calcium channels. Rosmarinic acid was found to be the active component.[50]

Smyrnium cordifoliumanimal (mice) PTZ223 mg/kgED50[35]

SuHeXiang Wananimal (mice) PTZInhalation for 3 hrs at a time, twice per day3 hr inhalation twice per day doubled onset latency of PTZ-induced seizures and abolished lethality. Effects were minimal for pcrotoxin and strychinine treated animals. Inhalation of the oil inhibited the activity of GABA transaminase, increasing GABA content and decreasing glutamate content in the brain to levels similar to controls. EO inhibited the binding of a GABA ligand at the benzodiazepine site.[64]

Terpinen-4-olanimal (mice) PTZ200 mg/kgIncreased latency period to PTZ-induced seizure 10 fold and latency to 2-MP induced seizure 5-fold, with activity comparable to 4 mg/kg DZP in both cases. Prevented 87% of seizures induced by PTZ. Alleviated 3-MP (a gaba antagonist) mediated convulsions. However, flumazenil didn't reverse the effect. Decreased I_Na through voltage-dependent sodium channels.[65]

Terpinen-4-olanimal (mouse) MES, PTZ, PCTX200 mg/kgSignificantly increased latency of convulsions and inhibited PCTX induced seizures[66]

Terpinen-4-olanimal (mouse) MES, PTZ, PCTX300 mg/kgDecreased tonic convulsions at 300 mg/kg.[66]

Terpineolanimal (mice) MES, PTZ, STRN-Increased latency period and decreased mortality in all models[54]

Tetrapleura tetrapteraanimal (mice) leptazol0.4 mLProtected 78% of animals at a dose of 0.4 mL.[67]

Thymoquinoneanimal (mice) PTZ93 mg/kgED50 for PTZ seizures[40]

1S-(-)-Verbenoneanimal (mice) PTZ200 mg/kgIncreased seizure latency more than ten-fold. Upregulated COX-2, BDNF and c-fos.[68]

Zataria Multifloraanimal (mice) PTZ, MES0.35 mL/kgSignificantly increased latency period for tonic convulsions and completely prevented tonic convulsions.[69]

Zhumeria majdaeanimal (mice) MES, PTZ0.26 mL/kgED50 for PTZ and MES induced convulsions[70]

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