Natural Anticonvulsants: A Review

 

Surendra Nath Pandeya*, Rajeev Kumar and Ashish Kumar Pathak

Medicinal Chemistry Research Laboratory, Department of Pharmacy, Saroj Institute of Technology and Management, Sultanpur Road, Lucknow, Pin-226002, U.P., India.

*Corresponding Author E-mail: snpande65@yahoo.co.in

ABSTRACT

Epilepsy is a neurological disorder affecting a large scale of the population, which accounts for about 1% of the world’s burden of diseases. A large number of agents called antiepileptic drugs are available to treat various types of seizures with the objective to reduce seizure frequency and severity within a framework of an acceptable level of side effects. There are number of 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. Herbal drugs are acting at target site having same mechanism of action as that of synthetic drugs. There is still a need for new antiepileptic drugs (AEDs), may be derived from natural sources, as the clinical efficacy tolerability, toxicity properties of existing synthetic AEDs may not be satisfactory. This review focuses on the use of natural products for control of epilepsy.

 

 

1-INTRODUCTION:

Epilepsy is a neurological disorder that affects a wide range of people throughout the world¹. Epilepsy has now become the most serious brain disorder, which accounts for about 1% of the world’s burden of diseases. Epilepsy is a neurological disorder characterized by excessive electrical discharge in brain, which cause seizures. The therapeutic strategy in countering epilepsy involves reducing neuronal excitability through different mechanistic pathways given in figure.

 

Most therapeutics currently used in the treatment of epilepsy is either directed toward blocking voltage-gated sodium and calcium channels or potentiating gamma amino butyric acid (GABA)-mediated neurotransmission, with little focus on voltage-gated potassium ion channels, despite these channels having a major role in the control of all aspects of neuronal excitability. It is reported that functional impairment of potassium in channels, either by mutation or inhibition result in epilepsy³. Incidence of epilepsy in developed countries is approximately 50 per 100,000 while that of developing country is 100 per 100,000 (WHO, 2006).  In many tropical countries the incidence of epilepsy was estimated to be greater than 0.5% of a given population and is higher in male than female with a majority having their first attack before the age of twenty⁴.

A number of synthetic antiepileptic drugs are available in practice, however their effectiveness does not hold true with the entire range of population suffering from this disorder. The conventional antiepileptic agents like phenytoin and sodium valporate carry with them several serious side effects notably neurotoxicity (given in table-1).

 

It has been observed that the presently available antiepileptic drugs are unable to control seizures effectively in as many as 25% of the patients.As majority of antiepileptic drugs are consumed life long, concomitant administration of other drugs predisposes to the risk of drug interaction (given in table-2).

 

The current therapeutic treatment of epilepsy with modern antiepileptic drugs (AEDs) is associated with side-effects, dose-related and chronic toxicity, and teratogenic effects, and approximately 30% of the patients continue to have seizures with current AEDs therapy. The currently available synthetic antiepileptic drugs provide seizure control in upto 70% patient with  epilepsy , the remaining patient have refractory epilepsy.

 

Thus there is still need to develop new drugs with greater clinical efficacy, tolerability minimal side effect, devoid of unfavorable drug interactions and better pharmacokinetic properties^4,5.

 

2-NATURAL PRODUCTS:

Traditional medicine involves the use of herbal medicine, animal parts and minerals. However, herbal medicines are the most widely used of the above three. Herbal medicines contain an active ingredient, aerial or underground parts of plants as their petal or seeds materials or combinations thereof, whether in the crude state or as plant preparations. Furthermore, about 80% of the world population is dependent (wholly or partially) on plant-based drugs (WHO, 1996)⁶.

 

    

On the other hand, the world health organization has estimated that perhaps 80% of the world’s population relies chiefly on traditional medicine for primary health care needs. Moreover, allopathic science may gain much from the study of such systems and important allopathic drugs like digitalis, quinine, atropine and several others have originated from plant sources. The discipline of Ayurveda (An alternative system of medicine) has existed in India from millennia with the objective to treat poor health with economical medicines obtained from herbs.

 

Likewise, different regions across the globe inherit their traditional system of medicine wherein, in today’s globalized era these traditional systems should not be restricted to their native origins but rather be made accessible and used throughout the human population. With this regards herbal anticonvulsants that are successfully exploited are reviewed as under⁷.

 

On the other hand, herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy coupled with least side effects, which in turn has accelerated the scientific research regarding the antiepileptic activity. Natural products have contributed significantly in the discovery of modern drugs and can be an alternative source for the discovery of AEDs with novel structures and better safety and efficacy profiles. Thus, it is necessary to investigate for an anti epileptic agent that is highly efficacious as well as safe in items of drug related toxicity¹.

 

An alternative to therapy for epilepsy could be from natural sources.These medicines may prove superior to synthetic drugs. A detailed account from various plant derived product are described in the given table (3).

 

Mechanism through which plants act as anticonvulsant agents:

It was thought that epileptic drugs inhibit seizure by regulating GABA mediated synaptic inhibition and /or by blocking post-synaptic 5-HT receptors and /or by inhibiting serotonergic transmission⁴⁴.

 

Bacopa monnieri:

The neuroprotective role of B.monnieri extract in alteration of glutamate receptor binding and gene expression of NMDA R1 in hippocampus of temporal lobe epileptic rats were observed. The neuroprotective role of B.monnieri extract in alteration of glutamate receptor binding and gene expression of NMDA R1 in hippocampus of temporal lobe epileptic rats were observed. In association with pilocarpine-induced epilepsy, there was significant down regulation of NMDA R1 gene expression and glutamate receptor binding without any change in its affinity. B.monnieri treatment of epileptic rats significantly reversed the expression of NMDA R1 and glutamate receptor binding alterations to near-control levels. Also, in the epileptic rats, it was observed a significant increase in the activity of glutamate dehydrogenase, which neared the control level after B. monnieri treatment¹⁰⁷.

 

Bryophyllum Pinnatum:

B. pinnatum aqueous extract might produce its central nervous system depressant action as consequence of its GABAergic and less importantly, glycinergic transmission, since picrotoxin is a selective GABAA receptor antagonist while strychnine antagonizes the inhibitory spinal cord and brainstem reflexes of glycine¹⁰⁹.

 

Cissus quadrangularis:

The inhibition by the extract of C. quadrangularis of STR-induced seizures suggests the presence of anticonvulsant properties and the involvement of glycine receptors. The sedative properties of C. quadrangularis could be related to the presence of some components in the extract activating the benzodiazepine and/or GABA recaptors in the GABA receptor complex²¹.

 

Cotyledon orbiculata:

Both aqueous and methanol extracts of Cotyledon orbiculata have anticonvulsant property and may probably be affecting both gabaergic and glutaminergic mechanisms to exert its anticonvulsant effect ²⁵.

 

Cyperus articulates:

Cyperus articulatus showed dose dependent reduction in spontaneous epileptic form discharge and NMDA induced depolarization in rat cortical wedge preparation at concentration at which L-amino-3-hydroxy-5methyl-isoxazole-4- propionic acid (AMPA)induced depolarization are not affected. This indicates that the extract may contain components acting as AMPA antagonist responsible for the possible antiepileptic action²⁷.

 

 

Table: 1

S. No	Classification	Drugs	Side effect
1-	Hydantion	Phenytoin	Nausea, skin rashes blood dyscarasias, hyperglycemia cardiac arrhythmias
2-	Barbiturate	Phenobarbital	Dizziness, lethargy, hypotension, aponea, megaloblastic anemia, Liver damage
3-	Iminostilbene	Carbamazepine   Eslicarbazepine	Dizziness, ataxia, drowsiness, hallucinations, dermatologic sweating, genitourinary albuminaria, hypotension, liver dysfunction. Nausea, Dizziness and headache
4-	Oxazolidinedione	Trimethadone	Drowsiness, G.I.distress, vertigo, diplopia, epistaxis, alopecia, nephrosis, foetal malformation .
5-	Deoxybarbiturate	Primidone	Lethargy, ataxia, vertigo, irritability, severe skin rashes, lymphadenopathy, impotence, visual disturbances, lupus like reactions
6-	Succinimide	Ethosuximide	G.I. distress, euphoria, confusion, myopia, urticaria, vaginal bleeding and
7-	Aliphatic carboxylic Acid	Sodium Valproate	Nausea, vomiting, indigestion, sedation, abdominal cramps, fetal hepatic failure, alopecia, irregular menses, acute pancreases, blood dyscarasias
8-	Phenyltriazine	Lamotrigine	Dizziness, ataxia, blurred vision, vomiting, skin rashes, Stevens Johnson syndrome, disseminated intravascular coagulation
9-	Aromatic allylc alcohol	Stiripentol	Loss of appetite, drowsiness,cognitive impairment, ataxia, diplopia, nausea, abdominal pain and occasionally asyptomatic neutropenia.
10-	Carbamoyl ethanol	Carisbamate	Dizziness, nausea, somnolence and headache.
11-	Triazole	Rufinamide	Vomiting, somnolence,pyrexia and diarrhoea.
12-	-	Lacosamide	Dizziness, nausea, somnolence, headache, Vomiting, blurred vision, diplopia and tremor.
13-	-	Retigabine	Sedation, dizziness, cognitive impairment, vertigo and diplopia
14-	-	Brivaracetam	Mostly  CNS-related

 

Table: 2   Common drug-drug interactions

S. No.	Antiepileptic drug	Other drugs	Interactions
1-	Phenytoin	Antacids Chlorpheniramine	Reduced serum phenytoin levels and thus loss of seizure control. Phenytoin intoxication
2-	Barbiturates	Caffeine Cimetidine /Ranitidine Codeine Felbamate Miconazole Rifampicin Sodium valproate	Reduces or abolishes the hypnotic effect of pentobarbitone Pentobarbitone reduces the absorption of cimitidine while cimitide increases metabolism of pentobarbitone Increases serum level of pentobarbitone. Increases serum level of pentobarbitone. Reduce in the activity of rifampicin by increase in the clearance. Increase in phenobarbitone level leading to excessive sedation. Decrease in serum phenobarbitone level
3-	Carbamazepine	Allopurinol Cholestyaramine/ Colestipol Cemitidine / Ranitidine Diuretics Isoniazid Metronidazole Primidone	Reduction in absorption of carbamazepine. Transient increase in serum carbamazepine. Leads to hyponatraemia. Marked increase in serum carbamazepine levels leading to toxicity. Marked increase in serum carbamazepine levels leading to toxicity. Carbamazepine levels are reduced leading to its poor seizure control
4-	Rufinamide	Oral hormonal contraceptives	May increase the clearance of Oral hormonal contraceptives as a result of a weak induction of CYP3A4.
5-	Carisbamate	Oral contraceptives	Reduction in Plasma concentration of Carisbamate by 20-30%
6-	Brivaracetam	Oral contraceptives	Slight reduction in absorption

 

 

Echium amoenum:

It is believed that plants of Boraginaceae family are rich of fatty acids, especially gamma linoleic acid and flavonoids. There are some evidences about anticonvulsat effect of this fatty acid and some flavonoid compound.the antiseizure effect of E.amoenum Fisch and C.A. Mey (F.M.) may be related in part to linoleic acid and/or flavonoid compounds present in the extrat⁴³.

 

Ferula gummosa:

Modulation of glutamatergic and GABAergic transmission is some mechanisms indicated for anticonvulsant action of the monoterpenes like linalool and eugenal.therefore,it seems that the antiseizure profile of F.gummosa root may be related in part to monoterpenes and terpenoid compounds present in the root⁵⁰.

 

Hypoxis hemerocallidea:

Hypoxis hemerocallidea aqueous extract produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain.⁵⁶

 

 

Harpagophytum procumbens:

H.procumbens secondary root aqueous extract produces its anticonvulsant activity by enhancing GABAergic neurotransmission and/or facilitating GABAergic action in the brain ⁶¹.

 

Wogonin

∆⁹  Tetrahydrocannabiol

 

Harpephyllum caffrum:

H.caffrum stem-bark aqueous extract might have inhibited and/or attenuated PTZ-and PCT-induced seizures of the mice used by enhancing, or in some way interfering with,GABAergic neurotransmission and/or action in the brain⁵⁷.

 

Glycyrrhiza glabra:

Anticonvulsant effects of the G. glabra extract could be related to the inhibitory effects of glycyrrhizic acid on gap junction channels.also,there is some evidence that glycyrrhetininic acid derivatives exert a variety   of effects such as altering the activity of ion transport processes including ion channels and inhibition Na⁺-K⁺-ATPase. Glycyrrhiza extract displays biochemical properties, all of  which are possible contributors to its anticonvulsant effects⁵⁴.

 

Gossypin:

Gossypin a bio-flavonoid exhibits anticonvulsant activity and the probable mode of action may be due to GABAaminergic mediation, glycine inhibitory mechanism and inhibit the electrical kindling effect¹.

 

Leonotis leonurus:

The extract of L. leonurus has anticonvulsant activity and may probably be acting through non-specific mechanisms, since it affects both gabaergic and glutaminergic systems⁶⁵.

 

Lavandula stoechas:

Lavandula stoechas caused a dose dependent (0.1–1.0mg/ml) relaxation of spontaneous contraction and inhibited K+ induced contractions thereby, suggesting calcium channel blockade. Further, pretreatment of the jejunum preparation with L. Stoechas produced a dose dependent shift of the Ca++ dose response curve to the right similar to the effect of standard calcium channel blocking activity ⁶⁸.

 

Mimosa pudica:

Mimosa pudica used in generalized clonic seizures in man (PTZ model) through GABAnergic neurotransmission. The inhibition of strychnine induced seizures highlights its indication through glycine receptors. Overall the study revealed anticonvulsant effect of the drug through modulation of multiple neurotransmission⁷².

 

Nardostachys jatamansi:

Nardostachys jatamansi root extract significantally increases  seizure threshold against maximal electroshock seizure (MES) model as indicated by a decrease in the extension/flexion (E/F) ratio⁷⁷.

 

Persea Americana:

Persea americana leaf aqueous extract (PAE) produces its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain⁸².

 

Pyrenacanthia staundtii:

Strychnine has been shown to induce convulsion by modulation of action of glycine on inhibitory neurotransmitter. However, the aqueous leaf extract of Pyrenacanthia staundtii  blocked the convulsion induced by strychnine indicating the involvement of glycinergic transmission. Picrotoxin is reported as GABA receptors antagonist  inducing convulsion, but the extract failed to block the convulsion induced by this agent. This indicates that the extract is not facilitating the GABA-ergic transmission ⁸³.

Table 3: Anticonvulsant properties of plant-products-

S.No	Plant Name	Family	Part Used	Solvent	Method	Ref.
1-	Acosmium subelegans	Leguminaceae,	Stem Barks	Ethanol	PTZ,MES	8
2-	Annona diversifolia Saff. and palmitone	Annonaceae	-	-	penicillin	9
3-   4-	Artemisia dracunculus   Artemisia verlotorum	Asteraceae (Compositae) -	Aerial parts -	-   Hydroalcoholic	PTZ,MES   PTZ,MES	10   11
5-	Aloe vera	Liliaceae	-	Ethanolic extracts	PTZ,MES	12
6-	Albizzia lebbeck	Mimosaceae	Leaves	Ethanolic extract	PTZ, electrical kindling and MES	13,14
7-	Ambrosia paniculata	-	Leaves	-	Isoniazid, PCT, and penicillin	15
8-	Acorus tatarinowii Schott	Araceae.	Rhizomes	Decoction and volatile oil extracted	PTZ,MES and prolonged PTZ kindling models	16
9-	Benincasa hispida	Cucurbitaceae.	Fruit	methanolic	PTZ, STR and PCT and MES	17
10-	Butea Monosperma	Fabaceae	Flowers	Petroleum ether extract	MES, PTZ, electrical kindling and combination of lithium sulphate with pilocarpine nitrate	11
11-	Cassia sophera	Caesalpiniaceae	Seed	Ethanol	PTZ,MES	18
12-	Crocus sativus	Iridaceae	Stigmas	Aqueous andethanol	PTZ,MES	19 and 20
13	Cissus quadrangularis   Cissus sicyoides	Vitaceae   Vitaceae	Stems   Leaves	Aqueous   Hydro-alcoholic extract	PTZ,MES, NMDA, isonicotinic hydrazid acid and STR   PTZ	21   22
14	Carissa edulis	Apocynaceae	Root bark	-	MES,PTZ	23  and 24
15-	Cotyledon orbiculata	Crassulaceae	Leaf	Aqueous and methanol	PTZ,PCT, BCL and NMDA	25
16-	Cissampelos mucronata	Menispermaceae	Root extract	ethanolic	PTZ,MES	26
17-	Cyperus articulates	Cyperaceae	Rhizomes	Methanolic ,aqueous extract,	PTZ, MES, STR and PCT	27
18-	Carissa edulis	Apocynaceae	Root bark	-	PTZ,MES	28
19-	Casimiroa edulis	Rutaceae	Seeds, Leaf	Aqueous, Methanol	PTZ,MES and rotarod	29,30
20-	Cestrum nocturnum Lin	Solanaceae	Leaves	Decoction	isoniazid and PCT, maximal electroshock seizures, penicillin	31
21-	Calotropis procera           Calotropis gigantean	Asclepiadaceae         Asclepiadaceae	Root           Roots	Chloroform, aqueous extract     Alcoholic extract	MES,PTZ, lithium-pilocarpine and electrical kindling seizures PTZ   -	32           33
22-	Calliandra portoricensis	-	Root and stem extracts	aqueous extracts	PTZ and electroshock-induced convulsions	34
23-	Centranthus longiflorus	-	-	Aqueous extract	Caffeine	35
24-	Citrus aurantium	Rutaceae	Peel and leaves	Hydroethanolic	PTZ,MES	36
25-	Cynodon dactylon	Graminae	Aerial parts	Ethanol extract	PTZ	37
26	Cymbopogon winterianus	Poaceae	Leaves	-	PTZ- and PIC	38
27-	Delphinium denudatum	Ranunculaceae	Roots	Ethanolic extract and aqueous fraction	MES, PTZ, BCL,PCT and STR	39,40
28-	Desmodium adscendens	Papillionaceae	Leaves	Ethanolic extract	PTZ	41
29-	Diospyros mespiliformis	Ebenaceae.	Stem bark	Aqueous extract	PTZ, rota-rod	42
30-	Echium Amoenam	Boraginaceae	Flower	Methenol	PCT	43
31-	Erythrina indica           Erythrina velutina and Erythrina mulungu.	Papilionaceae           Fabaceae	Leaves           Stem bark	Ethanol, Chloroform and Ethyl acetate extracts Hydroalcoholic extracts	PTZ,MES           PTZ STR,	44           45
32-	Eugenia caryophyllata	Myrtaceae	-	-	PTZ,MES	46
33-	Egletes viscose	-	Flower	Essential oil	PTZ	47
34-       35-	Ficus Sycomoros   F.religiosa   Ficus platyphylla	Moraceae Moraceae   -	Stem, Leaves     Stem bark	Ethenol -     Methanol extract	PTZ, STR PTZ     PTZ,MES and STR	4,48       49
36-	Ferula Gummosa	Apiaceae	Root,seed	Acetone	PTZ,MES and Rotarod	50,51
37-	Gossypin	Malvaceae	-	-	PTZ,MES,and STR	1
38-	Goodyera schlechtendaliana	-	Whole plants	-	PCT	52
39-	Ginseng	Araliaceae	Whole root leaves/stems extract, and a partially purified extract		PTZ, kainic Acid and,pilocarpine-induced seizures	53
40-	Glycyrrhiza glabra	Leguminosae	Root and Rhizome	Aqueous,Ethanol	PTZ	54,55
41-	Hypoxi hemerocallidea Fisch. and C. A. Mey.	Hypoxidaceae	Corm	Aqueous	PTZ,PCT,BCL	56
42-	Harpephyllum caffrum	Anacardiaceae	Stem	Aqueous extract	PTZ, PCT	57
43-	Heracleum crenatifolium Heracleum persicum	Umbelliferae	Fruits Seed	Acetone extract	MES PTZ,MES	58 59
44-	Hibiscus rosasinesis	Malvaceae	Flowers	Ethanolic Extract	PTZ,MES	11
45-	Hypericum perforatum	Hypericaceae	Aerial part	Aqueous and ethanol extract	PTZ,MES	60
46-	Harpagophytum procumbens DC	Pedaliaceae	Root	Aqueous extract	PTZ, PCT and BCL	61
47-	Ipomoea stans		Root	Ethyl acetate extract	PTZ	62
48-	Kalanchoe crenata (Andrews) Haworth	Crassulaceae	Leaves	Methylene chloride/methanol	PTZ, strychnine sulphate (STN) And thiosemicarbazide (TSC)	63
49-	Lecaniodiscus cupanioides	-	Root	Aqueous extract	STR ,PCT	64
50-	Leonotis leonurus	Lamiaceae	Leaves	Aqueous	PTZ, PCT,BCL and  NMDA	65
51-	laurus nobilis	Lauraceae	Leaf	-	MES and PTZ	66
52-	Lychnophora  rupestris and L. staavioides	Vernonieae, Asteraceae	Stem	Polar extracts and methanolic fractions	PTZ	67
53-	Lavandula stoechas	Labiatae	Flowers	Aqueous methanolic extract	PTZ	68
54-	Maprounea Africana	Euphorbiaceae	Leaves	Ethanolic extract	PTZ,	69
55-	Mitragyna africanus	Rubiaceae	Stem bark	Methanol extract	STR	70
56-	Mitragyna africanus	Rubiaceae	Stem bark	Methanol extract	STR	71
57-	Mimosa pudica	Mimosaceae	Leaf	Decoction	PTZ,PCT , STR and,NMDA	72
58-	Moringa oleifera	Moringaceae	Roots	Methanolic extract	PTZ, STR	73
59-	Myristica fragrans	Myristicaceae	Seeds	Petroleum Ether	PTZ,MES,PCT lithium pilocarpine	74
60-	Magnolia dealbata   Magnolia grandiflora	Magnoliaceae	Leaves   Seeds	Ethanol extract Ethyl ether (EE) and hydroalcoholic extract	PTZ   MES	75   76
61-	Nardostachys jatamansi	Valerianaceae	Roots	Ethanol	PTZ,MES	77
62-	Nigella sativa	Ranunculaceae	Seeds	-	PTZ,MES	78
63-	Nepeta sibthorpii	Labiatae (lamiaceae)	-	Methanol	PTZ	79
64-	Nylandtia spinosa L. Dumont	Polygalaceae	Leaf	Aqueous and methanol	PTZ, bicuculline, PCT, and NMDLA.	80
65-	Ocimum sanctum	Labiatae; Lamiaceae.	Stem, leaf and stem	Ethanol and chloroform extract	MES	81
66-	Persea Americana	Lauraceae	Leaf	Aqueous extract	PTZ,PCT, BCL	82
67-	Pyrenacanthia staundtii	Icacinacae	Leaf	Aqueous	PCT, STR	83
68-	Passiflora incarnate	Passifloraceae	Aerial parts (leaves, flower and fruit)	Hydro- alcoholic extract	PTZ	84
69-	Pimpinella anisum	Umbelliferae	Fruits	Aqueous	PTZ,MES	85
70-	Piper guineense	Piperaceae.	-	Water extract	NMDLA, PTZ,MES	86
71-	Petiveria alliacea	Phytolaccaceae	Root	Acetate, hexane,hydroalcoholic  and precipitated hydroalcoholic	Rotarod, PTZ	87
72-	Rosa damascena	Rasaceae	Petel		PTZ	88
73-	Rubus brasiliensis,	Rosaceae	Leaf	Ethanol	-	89
74-	Rhus chirindensis	Anacardiaceae	Stem-bark	Aqueous extract	PTZ, PCT and BCL	90
75-	Ruta chalepensis	Rutaceae.	Aerial parts	Ethanol extract	PTZ	91
76-	Sclerocarya birrea	Anacardiaceae	Stem bark	Aqueous extract	PTZ,PCT,BCL	92,93
77-	Scutellariae radix	Labiatae (lamiaceae)	Root	Water extract	MES, PTZ	94
78-	Sapindus trifoliatus	Sapindaceae	Fruits	Aqueous	PTZ,MES and rotarod	95
79-	Schumanniophyton magnificum	-	Roots	Ethanolic	PCT and STR	96
80-	Sutherlandia frutescens	Fabaceae	Shoot	Aqueous extract	PTZ, PCT and BCL	97
81-	Sesbania grandiflora	Papilionaceae; Fabaceae.	Leaves	-	PTZ and STR, lithium-pilocarpine	98
82-	Sanseviera liberica Gerome and Labroy	Agavaceae	Root	Aqueous	strychnine, picrotoxin, bicuculline and pentylenetetrazole	99
83-	Spondias mombin	Anacardiaceae.	Leaves	Aqueous, methanol and ethanol	PTZ, picrotoxin	100
84-	Taxus wallichiana	Taxaceae	Leaf	Methanol	PTZ	101
85-	Tetrapleura tetraptera	Fabaceae	Fruit	Aqueous extract	PTZ, PCT and BCL	103
86-     87-	Vitex-negundo Vitex negundo   Valeriana edulis	Verbenaceae Verbenaceae   -	Leaf Leaf   Roots	Ethanol Petroleum ether Hydroalcohol	PTZ,MES STR and leptazole rotarod	104 105   106
88-	Withania somnifera	Solanaceae	Root	-	PTZ	107

Pentylenetetrazole (PTZ), Picrotoxin (PCT) and Bicuculline (BCL), N-methyl-DL-aspartic acid( NMDA) and Strychnine (STR)

 

Rubus brasiliensis:

Rubus brasiliensis leaf ethanol extract was found to contain a benzodiazepine like principle and hence indicated possible involvement of GABA–A receptors. This involvement is further supported by reversal of anxiolysis in rodents induced by lumozenil, a specific GABA –A – benzodiazepine receptor antagonist⁸⁹.

 

Sclerocarya birrea:

Sclerocarya birrea produces its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain⁹².

 

Scutellaria baicalensis:

Wogonin is a natural product isolated from S. baicalensis, which possesses central nervous system effects such as anxiolytic and neuroprotective activities. Wogonin injected intraperitoneally 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 increased Cl-influx whereas Flumazenil and bicuculline inhibit it. These results indicate that the anticonvulsive effects produced by wogonin were mediated by the GABAergic neuron¹⁰⁸.

 

Sutherlandia frutescens:

S. frurescens shoot aqueous extract produces its antiseizure effect directly by acting like GABA, or indirectly by enhancing GABAergic neurotransmission and/or action in the brain.⁹⁷

 

Natural lead compounds:

The use of medicinal plants for the treatment of epilepsy and convulsive disorders dates back to prehistoric times. Several plants that were reputed to possess antiepileptic properties in different folklore cultures have been found to contain active ingredients when tested with modern bioassays for detecting anticonvulsive activities. This provides justification for their use in many different indigenous medicinal systems. The activity of many other plants however remains to be scientifically established. Ethnopharmacological research on natural products can contribute to the discovery of new active compounds with novel structures which may serve as leads to development of new antiepileptic drugs. An example is the isolation of the active alkaloid piperine from Piper nigrum L. which is one of the component herbs of an ancient Chinese medicine used for the treatment of epilepsy. Its structural modifications resulted in the synthesis of seven derivatives including antiepilepserine which was found to be more potent than the parent compound with fewer side effects and it has been used as an antiepileptic drug.

 

The aqueous extract as well as its albiflorin and pentagalloylglucose isolated from Paeonia albiflora (peony), a constituent of TJ 960, have strong inhibitory effect on PTZ induced EEG activity and Ca⁺⁺ and K⁺ ion concentration changes related to seizures. The extract has also shown to inhibit PTZ induced intracellular Ca⁺⁺ release and inward Ca⁺⁺ current. Methysticin, a kava pyrone isolated from the rhizomes of Piper methysticum(which is a shrub indigenous to south Pacific islands) and its dihydro derivative have neuroprotective effects in addition to anticonvulsant properties. Methysticin also inhibits seizure-like events in three different models of epileptiform activities in hippocampal and entorhinal cortex slices.

 

Linalool a monoterpene isolated from several species of aromatic plants including Aeolanthus suaveolens G.Dom., which is used for treatment of convulsions in Brazilian Amazon, has inhibitory effect on glutamate binding in rat cerebral cortex preparations. Baicalein isolated from TJ-960 exhibited strong in vitro radical scavenging and antioxidative activity. In FeCl3-induced epilepsy model it significantly decreased the level of free radicals at the injection site in the rat brain.

 

A number of highly addictive and toxic compounds have been isolated from these plants; including LSD,∆⁸ and ∆⁹ tetrahydrocannabinols, cannabidiol and cocaine. ∆⁸ and ∆⁹ tetrahydrocannabinols have anticonvulsant activity in various experimental models of epilepsy including kindling.

 

∆⁸  Tetrahydrocannabiol

 

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Received on 08.06.2009       Modified on 03.08.2009

Accepted on 10.09.2009      © RJPT All right reserved