Table 2.

Observed anticonvulsive and neuroprotective actions of exogenous antioxidants.

Substance	Cells/Animals/Humans	Seizure Model	References
Potential Antioxidant Actions
Ascorbic acid (vitamin C)
Ameliorates convulsive behaviour and neuronal death Inhibits initial oxidative stress & maintains GSH homeostasis Directly scavenges free radicals & restores the endogenous antioxidant system Enhances CAT activity and decreased LPO	Animal model (rats) Animal model (rats) Animal model (rats) Animal model (rats)	PIL/KA/PTZ Trimethylin Stress PIL	[89, 153, 163, 164] [165] [166] [89, 153]
β-catechin
Oral administration inhibits TBARS formation and increases the activity of SOD Pre-treatment results in a reduction in free radical formation	Animal model (rats) Animal model (rats)	Iron Iron	[167] [168]
Curcumin
Neuroprotective effects produced by:
maintenance of GSH levels inhibition of lipid peroxidation increase of heme oxygenase-1 expression Animal model mice/Astrocytes	Animal model (rats)	KA/- KA	[92, 169] [168]
Curcumin manganese complex
Possesses more powerful anticonvulsive and neuroprotective properties	Animal model (rats)	KA	[95, 170]
Animal models show it: mimic SOD activity exerts the activity of NO scavenging suppress markers indicating neuronal injuries	Animal model (rats)	KA	[95, 170]
Ginkgo biloba
Suppresses seizure generation and seizure induced ROS formation EGb 761 treated mice display attenuated response to PTZ pre-treatment protects against PTZ-induced convulsive behaviours neuroprotection correlates with antioxidant effects	Animal model (mice)	PTZ	[171]
*Neurotoxin (4’-O-methoxypridoxine) exerts pro-epileptic effects	Patients with epilepsy/Healthy subjects	/	[172]
Ginsenosides
Attenuate seizure activity block KA induced mitochondrial dysfunction and impaired mitochondrial antioxidant capacity attenuate ultrastructural mitochondrial damage & mitochondrial oxidative stress inhibit synaptosomal oxidative stress & presynaptic ultrastructural damage via adenosine A 2A receptor activation inhibit NMDA-mediated epileptic discharge	Animal model (rats) Animal model (rats) Animal model (rats) Animal model (rats)	KA PIL PTZ PTZ	[173] [173] [174] [174]
Honeybee propolis
Pre-treatment significantly attenuates oxidative stress, seizure activity and neuronal degenerations maintains GSH homeostasis maintains adenosine A1 receptor activation	Animal model (rats)	KA	[175]
Anticonvulsive actions markedly improves myoclonus decreases occurrence of generalized seizure gradually increases serum GSH levels	Animal model (rats)	Trimethylin/ KA	[165, 176]
Protects against seizures	Animal models (mice)	PTZ	[101]
Omega-3 fatty acids (PUFAs)
Exert channel modulation, and anti-inflammatory action DHA suppress epileptic seizures and synaptic transmission by blocking hippocampal frequency-dependent Na+ channels through inhibition of voltage-gated Ca2+ and Na+ channels, DHA enhance neuronal membrane stability	Animal model (rats) Animal model (rats/mice)	PIL KA	[103, 104, 177] [171, 174]
Observed anti-convulsive actions in animal studies suppress seizures and delay the latency to seizure onset delay the latency to seizure onset no changes in the latency to seizure onset suppress electrographic seizures reduce the frequency of severe seizures	Mice/rats Mice/rats Animal model (rats) Animal model (mice) Animal model (rats)	PTZ PTZ PTZ KA KA/GI	[105, 178] [106, 107, 179] [180, 181] [108] [182]
Anticonvulsant effects of n-3 PUFAs (EPA & DHA) in clinical studies [109] reduce seizure frequency by >50% transiently reduce seizure frequency	Patients with epilepsy Patients with epilepsy	CE Int./Ref.	[110] [111, 183]
Plasma concentrations are elevated in children treated with KD	Children with epilepsy	KD	[184]
Resveratrol
Exerts anticonvulsive and neuroprotective properties, decreases LPO Delays the onset of seizures and decreases LPO	Animal model (mice/rats) Animal model (rats)	KA/AOMS Iron	[171, 185] [186]
α-Tocopherol(vitamin E)
Pre-treatment with α-tocopherol: decreases the percentage of animals with seizures, increases time needed to trigger the first seizure, increases survival, decreases LPO and nitrite content, increases SOD and CAT activity	Animal model (rats)	PIL	[122, 125]
Prevents the development of epileptic seizures induced by iron administration Significantly delays the appearance of seizures triggered by intracerebral FeCl3 administration Decreases seizure activity and LPO Improvement in patients with complex partial seizures Exerts anticonvulsive and neuroprotective effects - reduced BBB disruption Fails to attenuate seizure activity	Animal model (rats) Animal model (rats) Animal model (rats) Patients with epilepsy Animal model (rats) Animal model (rats)	Iron Iron Iron - PTZ KA/Amig. kindl./BIC	[135, 187, 188] [135, 187, 188] [189, 190] [191] [92-194] [115, 191] [191, 189]

AOMS - artery occlusion model of stroke, CE – chronic epilepsy, DHA - docosahexaenoic acid, EPA - eicosapentaenoic acid, GI – global ischemia, GSH – glutathione, Int. – Intractable, KA – kainic acid, KD – ketogenic diet, LPO- lipid peroxidation, NMDA - N-methyl-D-aspartate, PIL – pilocarpin, PTZ – pentylenetetrazol, PUFA - polyunsaturated fatty acid, Ref. – refractory, SOD - superoxide dismutase, * Ginkgo biloba extracts can contain neurotoxin (4’-O-methoxypridoxine) which can exert pro-epileptic effects.