Seizure and Epilepsy and the Seed

Dr. Weeks’ Comment:  Seizures are driven by inflammation. What follows below are 10 articles from PubMed which the search terms “inflammation” and “seizure” and what we learn is that inflammation drives epilepsy and seizure and autism and other neuro-inflammatory cytokine storms. Black cumin seed is a powerful and safe anti-inflammatory food and it is always best to eat the whole seed and not buy a bottle of extracted seed oil which oxidizes as soon as the bottle cap is removed.

Med Sci Monit . 2007 Dec;13(12):CR555-9.

The effect of Nigella sativa L. (black cumin seed) on intractable pediatric seizures

Javad Akhondian 1 , Ali ParsaHassan Rakhshande


Background: 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.

Results: The mean frequency of seizures decreased significantly during treatment with extract (p<0.05).

Conclusions: It can be concluded that the water extract of Nigella sativa L. has antiepileptic effects in children with refractory seizures.


Epileptic Disord . 2013 Sep;15(3):295-301. doi: 10.1684/epd.2013.0602.

The clinical outcome of adjuvant therapy with black seed oil on intractable paediatric seizures: a pilot study

May Shawki 1 , Lamia El WakeelRania ShatlaGamila El-SaeedSamira IbrahimOsama Badary


Aim: To evaluate the effect of black seed oil, as add-on treatment to antiepileptic drugs (AEDs), on seizure frequency and severity as well as oxidative stress in intractable epilepsy patients.

Results: 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.

Conclusion: 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.


Transl Neurosci. 2017 Mar 25;8:9-14. doi: 10.1515/tnsci-2017-0003. eCollection 2017 Jan.

Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model

Yi-Ye Shao 1 , Bing Li 2 , Yong-Mei Huang 1 , Qiong Luo 1 , Yang-Mei Xie 1 , Ying-Hui Chen 1

Affiliations expand

Free PMC article


Aim: Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway.

Results: Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus.

Conclusion: These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway.



Biomed Pharmacother. 2016 Oct;83:635-640. doi: 10.1016/j.biopha.2016.07.018. Epub 2016 Jul 25.

Thymoquinone: An edible redox-active quinone for the pharmacotherapy of neurodegenerative conditions and glial brain tumors. A short review

Ilhan Elmaci 1 , Meric A Altinoz 2


There exist few efficient agents in the neurological and neurosurgical armamentarium for treatment of neurotrauma, refractory seizures and high grade glial tumors. Pathophysiological conditions of diverse neural injuries have converging common pathways including oxidative stress and apoptosis. Targeted therapies have been throughly investigated, but limited success has been achieved until now. Phytochemical drugs may provide easily achievable and cheap adjunctive sources. Thymoquinone is an edible quinone obtained from Nigella sativa seed oil and exerts powerful antiinflammatory, antioxidant and antitumor activities in experimental models. Recently emerging studies conducted with animal models suggest that thymoquinone – bearing a very simple molecular structure – significantly crosses the blood brain barrier and exerts neuromodulatory activities. Indeed, in animal studies, the following actions of thymoquinone were demonstrated: 1-Protection against ischemic brain damage. 2-Reduction of epileptic seizures and associated cerebral oxidative injury. 3-Reduction of morphine tolerance and associated oxidative brain damage. 4-Anxiolytic effects and reduction of immobility stress-associated cerebral oxidative injury. 5-Reduction of diabetes-induced cerebral oxidative stress, 6-Reduction of cerebral oxidative injuries induced by noxious exposures including toluene, lead and ionizing radiation. Substantial in vitro data suggest that thymoquinone may be beneficial in treatment of glial tumors. However, there is no clinical study investigating its antitumor effects. In fact, thymoquinone suppresses growth and invasion, and induces apoptosis of glial tumor cells via degrading tubulins and inhibiting 20S proteasome, telomerase, autophagy, FAK and metalloproteinases.A simple and easily available agent may be a promising adjunctive treatment option in neurological and neurosurgical practice.



Phytomedicine. 2004 Jan;11(1):56-64. doi: 10.1078/0944-7113-00376.

Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice

H Hosseinzadeh 1 , S Parvardeh


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.


Neurochem Res. 2016 Dec;41(12):3399-3406. doi: 10.1007/s11064-016-2074-y. Epub 2016 Oct 18.

Protective Effects of Thymoquinone Against Convulsant Activity Induced by Lithium-Pilocarpine in a model of Status Epilepticus

Yiye Shao 1 , Yonghao Feng 1 , Yangmei Xie 1 , Qiong Luo 1 , Long Chen 1 , Bing Li 2 , Yinghui Chen 3


Inflammation plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black seed (Nigella sativa) oil, which has anti-inflammatory properties in the context of various diseases. This study explored the protective effects of TQ in SE and used a lithium-pilocarpine model of SE to investigate the underlying mechanism, which was related to inflammation mediated by the NF-κB signaling pathway. In the present study, latency to SE increased in the TQ-pretreated group compared with the SE group, and the incidence of SE was significantly reduced. The seizure severity score measured on the Racine scale was significantly decreased in the TQ group compared with the SE group. Moreover, the results of the behavioral tests suggested that TQ may also have a protective effect on learning and memory functions. Finally, we further investigated the protective mechanism of TQ. The results showed that TQ-pretreatment significantly downregulated the protein levels of COX-2 and TNF-α in the brain, in a manner mediated by the NF-κB signaling pathway. These findings demonstrate that TQ attenuates convulsant activity via an anti- inflammation signaling pathway in a model of SE.


Pharmacogn Mag. 2015 May;11(Suppl 1):S182-9. doi: 10.4103/0973-1296.157729.

Neuroprotective effects of Nigella sativa extracts during germination on central nervous system

Mohammad Hayatul Islam 1 , Iffat Zareen Ahmad 1 , Mohammad Tariq Salman 2

Free PMC article


Background: 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.

Results: 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. sativa extracts 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.

Conclusion: 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.



Neurochem Res. 2016 Dec;41(12):3386-3398. doi: 10.1007/s11064-016-2073-z. Epub 2016 Oct 18.

Nigella sativa Oil Reduces Extrapyramidal Symptoms (EPS)-Like Behavior in Haloperidol-Treated Rats

Tafheem Malik 1  2  3 , Sheema Hasan 4 , Shahid Pervez 4 , Tasneem Fatima 5 , Darakhshan Jabeen Haleem 6  7


The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1 mg/kg) on NS (0.2 ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls. Immunohistochemical analysis indicates that NS reduced astrogliosis in caudate and accumbens nuclei. These results suggest that NS may consider as an adjunct to antipsychotics to reduce the EPS-like side effect.


Med Sci Monit. 2005 Apr;11(4):BR106-10. Epub 2005 Mar 24.

Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats

Hossein Hosseinzadeh 1 , Siavash ParvardehMarjan Nassiri-AslMohammad-Tagi Mansouri


Background: 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.

Results: 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.).

Conclusions: These results indicate that thymoquinone may have anticonvulsant activity, probably through an opioid receptor-mediated increase in GABAergic tone.



Int J Health Sci (Qassim). 2008 Jan;2(1):15-25.

Potentiation of Valproate-induced Anticonvulsant Response by Nigella sativa Seed Constituents: The Role of GABA Receptors

Muhammad Raza 1 , Abdullah A AlghashamMohammad S AlorainyTarig M El-Hadiyah


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.

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