Effects of thymoquinone, the major constituent of <i>Nigella sativa</i> seeds, on penicillin-induced epileptiform activity in rats

Beyazçiçek, Ersin; Ankaralı, Seyit; Beyazçiçek, Özge; Ankaralı, Handan; Demi̇r, Şerif; Özmerdivenli, Recep

doi:10.17712/nsj.2016.2.20150781

Cited by 19 publications

(19 citation statements)

References 30 publications

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“…In a penicillin-induced epilepsy model, TQ also has antiepileptic activity in rats. Various doses of TQ (10, 50, and 100 mg/kg) significantly increase the latency time to the onset of the first spike wave and decrease the frequency and amplitude of epileptiform activity over the first 20 minutes compared with the control group [ 33 ]. In another epileptic model, kainic acid (0.5 μ g/ventricle i.c.v.)…”

Section: Neuropharmacological Potential Of Thymoquinonementioning

confidence: 99%

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders

Jakaria

Cho

Haque

et al. 2018

Oxidative Medicine and Cellular Longevity

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Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa and has various pharmacological activities, such as protection against oxidative stress, inflammation, and infections. In addition, it might be a potential neuropharmacological agent because it exhibits versatile potential for attenuating neurological impairments. It features greater beneficial effects in toxin-induced neuroinflammation and neurotoxicity. In various models of neurological disorders, it demonstrates emergent functions, including safeguarding various neurodegenerative diseases and other neurological diseases, such as stroke, schizophrenia, and epilepsy. TQ also has potential effects in trauma mediating and chemical-, radiation-, and drug-induced central nervous system injuries. Considering the pharmacokinetic limitations, research has concentrated on different TQ novel formulations and delivery systems. Here, we visualize the neuropharmacological potential, challenges, and delivery prospects of TQ, specifically focusing on neurological disorders along with its chemistry, pharmacokinetics, and toxicity.

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Section: Neuropharmacological Potential Of Thymoquinonementioning

confidence: 99%

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders

Jakaria

Cho

Haque

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Epilepsy is not only a disease, but also a symptomatic condition caused by genetic factors, traumatic brain injury, central nervous system infections, stroke, or structural brain lesions including brain tumors. In spite of detailed investigations, the underlying etiology cannot be found in approximately 65% of patients 1,2 .…”

Section: Introductionmentioning

confidence: 97%

“…In addition, the side effect profiles of existing drugs used in antiepileptic treatment are quite extensive. Therefore, efforts to find more effective antiepileptic drugs with low side effect profiles and elucidate the mechanisms of epilepsy are still in progress today 1 .…”

Section: Introductionmentioning

confidence: 99%

The effect of vortioxetine on penicillin-induced epileptiform activity in rats

Öğün

Çetinkaya

Beyazçiçek

2019

Arq. Neuro-Psiquiatr.

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Vortioxetine is a multimodal antidepressant agent that modulates 5-HT receptors and inhibits the serotonin transporter. It is indicated especially in cases of major depressive disorder related to cognitive dysfunction. There are many studies investigating the effects of antidepressants on the seizure threshold and short-term epileptic activity. However, the effect of vortioxetine on epileptic seizures is not exactly known. Our aim was to investigate the effects of vortioxetine on penicillin-induced epileptiform activity. Twenty-seven Wistar rats were divided into three groups: sham-control group, positive control group (diazepam), and vortioxetine group. After a penicillin-induced epilepsy model was formed in each of the three groups of animals, 0.1 ml of saline was administered to the control group, 0.1 ml (10 mg/kg) vortioxetine was administered in the vortioxetine group, and 0.1 mL (5 mg/kg) of diazepam was administered in the positive control group, intraperitoneally. The epileptic activity records were obtained for 120 minutes after the onset of seizure. There was no significant difference in spike wave activity between the vortioxetine and diazepam groups, whereas this was significantly reduced in the vortioxetine group compared with the controls. The administration of vortioxetine at a dose of 10 mg/kg immediately after the seizure induction significantly decreased the spike frequencies of epileptiform activity compared with the control group. No significant difference was found between the vortioxetine and positive controls. This study showed that vortioxetine reduces the number of acutely-induced epileptic discharges. Vortioxetine may be an important alternative for epileptic patients with major depressive disorder-related cognitive dysfunction.

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“…injection) increased the latency to tonic-clonic seizures in the PTZ model [38]. THQ reduced spike wave incidence and severity of epileptic activity in penicillin-provoked seizures [39]. THQ reduced seizure severity by rising Nrf2, HO-1 proteins and SOD in the Li-pilocapine model [40].…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone Potentiates the Effect of Phenytoin against Electroshock-Induced Convulsions in Rats by Reducing the Hyperactivation of m-TOR Pathway and Neuroinflammation: Evidence from In Vivo, In Vitro and Computational Studies

et al. 2021

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Epilepsy is a chronic neurodegenerative disease characterized by multiple seizures, hereto 35% of patients remain poor responders. Phenytoin (PHT; 20 and 40 mg/kg) and thymoquinone (THQ; 40 and 80 mg/kg) were given alone and as a low dose combination for 14 days (p.o), prior to challenge with maximal electroshock (MES; 180 mA, 220 V, 0.2 s). Apart from observing convulsions, hippocampal mTOR, IL-1β, IL-6 and TNF-α levels were measured. Hippocampal histomorphological analysis was also conducted. In vitro cell line studies and molecular docking studies were run in parallel. The results revealed the synergistic potential of the novel duo-drug combination regimen: PHT (20 mg/kg) and THQ (40 mg/kg) against MES-induced convulsions. MES amplified signaling through mTOR, and inflated the levels of proinflammatory markers (IL-1β, IL-6 and TNF-α), which was significantly averted (p < 0.001) with the said drug combination. The computational studies revealed that PHT and THQ cooperatively bind the active site on Akt (upstream target of m-TOR) and establish a good network of intermolecular interactions, which indicates the sequential inhibition of PI3K/Akt/m-TOR signaling with the combination. The combination also increased cell viability by 242.81% compared to 85.66% viability from the the toxic control. The results suggest that the PHT and THQ in combination possesses excellent anticonvulsant and neuroprotective effects.

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Effects of thymoquinone, the major constituent of Nigella sativa seeds, on penicillin-induced epileptiform activity in rats

Cited by 19 publications

References 30 publications

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders

The effect of vortioxetine on penicillin-induced epileptiform activity in rats

Thymoquinone Potentiates the Effect of Phenytoin against Electroshock-Induced Convulsions in Rats by Reducing the Hyperactivation of m-TOR Pathway and Neuroinflammation: Evidence from In Vivo, In Vitro and Computational Studies

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