Dr. Weeks’ Comment: Black Cumin seed, grape seed and D- ribose – all ingredients in SOUL – the crushed whole seed anti-inflammatory drink – all have been found to offer benefits to those with seizures.
Black Cumin Seed (Thymoquinone) and Seizure Reduction
Nigella sativa Linn. which has many acclaimed medicinal properties is an indigenous herbaceous plant and belongs to the Ranunculaceae family, which grows in countries bordering the Mediterranean Sea, Pakistan and India.
This study was designed to investigate the effects of N. sativa seed extracts of different germination phases on the central nervous system (CNS) responses in experimental animals.
All tested extracts of N. sativa during different phases of germination (especially 5(th) day germination phase) showed significant (P < 0.001) anxiolytic effect in comparison to control. Diazepam reduced locomotor activity in control (unstressed) rats but did not show affect in stressed rats while N. sativaextracts from germination phases significantly (P < 0.001) reduced locomotor activity in unstressed as well as stressed animals. All the extracts of N. sativa from different germination phases exhibited significant (P < 0.001) reduction in various phases of epileptic seizure on comparison with the reference standard (diazepam). During antidepressant test, N. sativa extracts exhibited a slight reduction in the immobility of rats.
During germination, especially in 5(th) day germination extract, N. sativa showed significant CNS depressant activity as compared to whole seeds that possibly may be due higher content of secondary metabolites produced during germination.
The clinical outcome of adjuvant therapy with black seed oil on intractable paediatric seizures: a pilot study.
To evaluate the effect of black seed oil, as add-on treatment to antiepileptic drugs (AEDs), on seizurefrequency and severity as well as oxidative stress in intractable epilepsy patients.
At baseline, both groups (I, II) had significantly lower serum TAC levels relative to healthy controls (p=0.007), while MDA levels were unchanged. After the 4-week period of black seed oil administration, there was no significant difference between the two groups with regards to seizure frequency, severity, or oxidative stress markers (TAC and MDA; p>0.05). Eight patients had >50% reduction in seizure frequency/severity after black seed oil versus placebo.
Children with intractable epilepsy show evidence of oxidative stress. Administration of 40-80 mg/kg/day of black seed oil as add-on therapy did not alter either oxidative stress markers or seizure frequency or severity in intractable epileptic patients.
Potentiation of Valproate-induced Anticonvulsant Response by Nigella sativa SeedConstituents: The Role of GABA Receptors.
This study investigated antiepileptic effects of the main constituents of Nigella sativa (NS) seed (i.e. aqueous extract (AE), fixed oil (FO), volatile oil (VO)) and the main components of its VO (i.e. thymoquinone, α-pinene and p-cymene) using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced convulsions. The potential of these constituents to induce minimal neurological deficit (MND) was also evaluated by using chimney test.Except for the FO, all of the NS seed constituents protected mice effectively against PTZ-induced convulsions. The activity of the VO in this model maybe attributed mainly to its content of thymoquinone and p-cymene and to a lesser extent, α-pinene. VO and its component p-cymene effectively suppressed convulsions induced by MES. The contents of p-cymene present in the effective dose of the VO maybe partially responsible for its anti-seizure effects.All of the NS seed constituents induced varying degrees of MND in the chimney test. MND induced by VO may pertain to its contents of thymoquinone (63%), p-cymene (23%) and α-pinene (<14%). Protective indices of p-cymene and thymoquinone were closer to one, but only in PTZ model.Exploration on the role of receptors suggests that picrotoxin and bicuculline-sensitive GABA receptors, most probably GABAA receptors, mediate an increase in GABAergic response. In the part dealing with the interaction of valproate with thymoquinone, it can be mentioned that thymoquinone increased the potency of valproate in both PTZ and MES models.
Despite the availability and use of numerous antiepileptic drugs (AEDs), nearly 15% of childhood epilepsy cases are resistant to treatment. However, in traditional medicine, Nigella Sativa L. (“black cumin seed“) has been known for its anticonvulsant effects. This plant is naturally distributed in Iran and has been widely used as a natural remedy for a long time. In this study the efficacy of this agent in reducing the frequency of seizures in childhood refractory epilepsy was assessed.
The mean frequency of seizures decreased significantly during treatment with extract (p<0.05).
It can be concluded that the water extract of Nigella sativa L. has antiepileptic effects in children with refractory seizures.
Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats.
Recently we investigated some neuropharmacological aspects of thymoquinone, such as anticonvulsant, muscle relaxant, and hypnotic effects, as well as its effect on motor coordination and locomotor activity. In this study, we evaluated the effect and mechanism(s) of the action of thymoquinone more precisely via intracerebroventricular (i.c.v.) injection.
In PTZ-induced epileptic seizures, the i.c.v. injection of thymoquinone at doses of 200 and 400 microM prolonged the time until onset and reduced the duration of tonic-clonic seizures. The protective effect of thymoquinone against lethality was 45% and 50% in the respective doses. In this study, flumazenil (1 nM, i.c.v.) reversed the anticonvulsant activity of thymoquinone. Also, pretreatment with naloxone (10 microM, i.c.v.) antagonized the prolongation of tonic-clonic seizure latency as well as the reduction in seizure duration induced by thymoquinone (200 microM, i.c.v.).
These results indicate that thymoquinone may have anticonvulsant activity, probably through an opioid receptor-mediated increase in GABAergic tone.
The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizure models. We also studied the effect of thymoquinone on pentobarbital-induced hypnosis, locomotor activity, and motor coordination. In PTZ-induced seizure, the intraperitoneally injection of thymoquinone with doses of 40 and 80 mg/kg, prolonged the onset of seizures and reduced the duration of myoclonic seizures. The protective effect of thymoquinone against mortality was 71.4% and 100% in the mentioned doses, respectively. In MES model, thymoquinone failed to reduce the duration of seizure, whereas exhibited a complete protection against mortality. In PTZ model, flumazenil (10 mg/kg, i.p.), an antagonist of benzodiazepine (BZD) site in the GABAA-BZD receptor complex, inhibited the prolongation of seizure latency, but did not show any effect on the duration of myoclonic seizures. Also, pretreatment with naloxone (0.1 and 03 mg/kg, i.p.) inhibited the prolongation of myoclonic seizure latency and antagonized the reduction of myoclonic seizure duration induced by thymoquinone (40 and 80 mg/kg) in the PTZ model. Moreover, thymoquinone (40 and 80 mg/kg) did not have any hypnosis effect in the pentobarbital-induced hypnosis, but impaired the motor coordination and reduced the locomotor activity. These results indicate that thymoquinone may have anticonvulsant activity in the petit mal epilepsy probably through an opioid receptor-mediated increase in GABAergic tone.
Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats.
Numerous studies have demonstrated the antioxidant effects of grape seed proanthocyanidin extract (GSPE). The generation of free radicals and the ensuing apoptosis may contribute to the pathogenesis of epilepsy; therefore, in the present study, we examined the effects of GSPE on cognitive impairment and neuronal damage induced by chronic seizures in rats. Seizures were induced by a daily intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ; 35 mg/kg/day, 36 days). Two other groups were treated with GSPE (100 or 200 mg/kg/day, orally) for 24 days and then for 36 days prior to each PTZ injection. After the final PTZ injection, hippocampus-dependent spatial learning was assessed using the Morris water maze (MWM). The rats were then sacrificed for the measurement of hippocampal malondialdehyde (MDA, a measure of lipid peroxidation) and glutathione (GSH, a measure of endogenous antioxidant capacity) levels, and for the expression of pro-apoptotic factors [cytochrome c (Cyt c), caspase‑9 and caspase‑3]. The mitochondrial generation of reactive oxygen species (ROS), degree of mitochondrial swelling, neuronal damage and mitochondrial ultrastructure were also examined. Performance in the MWM was markedly impaired by PTZ-induced seizures, as evidenced by longer escape latencies during training and fewer platform crossings during the probe trial. This cognitive decline was accompanied by oxidative stress (MDA accumulation, ROS generation, reduced GSH activity), an increased expression of pro-apoptotic proteins, as well as damage to CA1 pyramidal neurons and the mitochondria. Pre-treatment with GSPE dose‑dependently reversed PTZ-induced impaired performance in the MWM, oxidative stress, mitochondrial ROS generation, the expression of pro-apoptotic proteins and neuronal and mitochondrial damage. Thus, GSPE may reverse the hippocampal dysfunction induced by chronic seizures, by reducing oxidative stress and preserving mitochondrial function.
Flavan-3-ol compounds prevent pentylenetetrazol-induced oxidative damage in rats without producing mutations and genotoxicity.
Seizure disorder is a chronic condition in the brain that affects approximately 50 million people worldwide. Oxidative stress plays a crucial role in the pathophysiology of this disorder and can cause neuronal injury. Approximately one in three treated patients suffers from seizures regardless of pharmacological intervention, which results in oxidative damage. The present study aims to investigate the possible protective effect of antioxidant-rich Vitis labrusca extract on pentylenetetrazol-induced oxidative damage in Wistar rats. Possible behavioral alterations, genotoxic and mutagenic effects of the extract were also evaluated. The results showed that V. labrusca extract provides a significant protective effect against oxidative damage to lipids and proteins induced by pentylenetetrazol in the cerebral cortex, cerebellum, hippocampus and liver of rats. Also, the extract did not alter locomotor behavior. Moreover, it was non-genotoxic and non-mutagenic. Our results suggest the possibility of using V. labrusca extract as a therapeutic agent to minimize neuronal damage associated with seizures.
Effect of D-ribose on purine synthesis and neurological symptoms in a patient with adenylosuccinase deficiency.
Oral supplementation of 10 mmol/kg/day of D-ribose to a patient with an inherited deficit of adenylosuccinase, severe psychomotor retardation, and epilepsy caused a marked increase in plasma concentration and urinary excretion of urate, while minor changes in succinylpurine levels were observed. D-Ribose administration was accompanied by a slight improvement of behaviour and a progressive reduction of seizure frequency, which increased dramatically upon two attempts to withdraw the drug. Substitution of D-ribose with an equivalent amount of D-glucose did not result in an increase of seizure frequency.