Neuroprotective Effects Of Thymoquinone Research Articles

Antioxidant Thymoquinone and Its Potential in the Treatment of Neurological Diseases.

Oxidative stress is one of the main pathogenic factors of neuron damage in neurodegenerative processes; this makes it an important therapeutic target to which the action of neuroprotectors should be directed. One of these drugs is thymoquinone. According to modern data, this substance has a wide range of pharmacological activity, including neuroprotective, which was demonstrated in experimental modeling of various neurodegenerative diseases and pathological conditions of the brain. The neuroprotective effect of thymoquinone is largely due to its antioxidant ability. Currently available data show that thymoquinone is an effective means to reduce the negative consequences of acute and chronic forms of cerebral pathology, leading to the normalization of the content of antioxidant enzymes and preventing an increase in the level of lipid peroxidation products. Antioxidant properties make this substance a promising basis for the development of prototypes of therapeutic agents aimed at the treatment of a number of degenerative diseases of the central nervous system.

Effects of Thymoquinone (TQ) on the Molecular Structure and Total Antioxidant Capacity of Cerebellum Tissue of Healthy Rats

Objective: The neuroprotective effects of thymoquinone (TQ), the active compound of Nigella sativa, have been reported in accordance with the anti-inflammatory and antioxidant features of this drug. It has been suggested that the cerebellum plays a considerable role in neurodegenerative processes. In the current study, the possible effects of TQ on the structure and composition of cerebellum tissues and its total antioxidant capacity were studied dose-dependently. Materials and Methods: Fifteen adult Long Evans female rats were divided into groups as follows: G1: Control, G2: 10 mg/kg TQ treatment, G3: 20 mg/kg TQ treatment. TQ was injected into the rats intraperitoneally for two weeks. The control group only received corn oil used for the dissolving of TQ. Fourier-transform infrared spectroscopy (FTIR) studies and total protein, and antioxidant capacity measurements were carried out with cerebellum tissues which were removed following the decapitation of rats. Results and Conclusion: 10 mg/kg TQ treatment improved the saturated and unsaturated lipid and protein content in addition to decreasing nucleic acid content and lipid peroxidation and increasing the total antioxidant capacity of cerebellum tissues. However, 20 mg/kg TQ treatment did not have any significant effect.

Thymoquinone has a synergistic effect with PHD inhibitors to ameliorate ischemic brain damage in mice

BackgroundA blockage in a blood vessel can cause reduced blood flow to the brain, which eventually leads to the death of surrounding tissue. Several studies have attempted to develop an effective intervention to reverse this process and improve the health status of affected individuals. Due to its indirect effect on cellular functions and metabolism, the hypoxia-inducible factor (HIF-1α) protein has been proposed as a promising transcription factor in the treatment of stroke. PurposeThe current study aims to explore the relation between HIF-1 α and thymoquinone (TQ) in the attenuation of ischemic brain damage and the possible mechanism of this relation to reduce cell death. MethodsFor this purpose, dimethyloxallyl glycine (DMOG), 8 mg/kg, Acriflavine (ACF), 1.5 mg/kg, and both combined with TQ (5 mg/kg) were assessed. Male C57 mice were used to establish an ischemic stroke model by using endothelin-1 (ET-1) (400 pmole/μl) intra- cranial injection. The ultrastructure alterations of neuronal soma, axons, and mitochondria after stroke and treatment were well addressed. Besides, the expression levels of VEGF, HIF-1α, Nrf2, and HO-1 were evaluated. Meanwhile, apoptosis and autophagy-related proteins were also investigated. ResultsTreatment of ischemic stroke by TQ can activate the HIF-1α pathway and its downstream genes such as VEGF, TrkB, and PI3K, which in turn enhance angiogenesis and neurogenesis. Our study revealed that TQ has the same effect as DMOG to activate HIF-1 α and can improve motor dysfunction after ischemic stroke. Further, we demonstrated that both TQ and DMOG effectively attenuate the organelle's damage following ischemic stroke, which was confirmed by the cryogenic transmission electron microscope. The synergistic effect of TQ and DMOG may lead to a chemo-modulation action in the autophagy process after stroke onset and this result is validated by the western blot and rt-qPCR techniques. ConclusionOur finding revealed the potential role of TQ as a HIF-1 α activator to reduce cell death, modulate autophagy and decrease the infarct volume after ischemic stroke onset. The neuroprotective effect of TQ is achieved by decreasing the inflammation and increasing angiogenesis as well as neurogenesis via induction of the HIF-1α-VEGF/Nrf2-HO-1-TrkB-PI3K pathway.

Acute and subacute effects of thymoquinone on acute methanol intoxication: An assessment based on serum TBARS and BDNF levels in rat model

Objectives: Previous studies have shown the role of oxidative stress in methanol (MeOH) neurotoxicity. In clinical practice ethanol (EtOH) was used for the treatment of MeOH intoxication. Treatment with EtOH results in depression of the central nervous system, which may occur even at therapeutic doses. It also induces oxidative stress. Antioxidant and neuroprotective effects of thymoquinone (TQ) are known in different models of neurotoxicity. There are no studies investigating the protective effect of TQ against acute MeOH intoxication. We aimed to evaluate the effect of TQ administration on serum thiobarbituric acid reactive substances (TBARS) and Brain-Derived Neurotrophic Factor (BDNF) levels in rats with experimentally-induced MeOH intoxication. Materials and Methods: Six groups were constituted. Methotrexate (Mtx) treatment (0.3 mg/kg/day) intraperitoneally (i.p.) was given for 7 days to slow down the formate metabolism of all rats except controls in order to create a MeOH intoxication similar to that in humans. On the 8th day of the experiment, 3 g/kg MeOH was injected i.p. in MeOH, EtOH and TQ groups. Four hours after MeOH administration, 0.5 g/kg EtOH was injected i.p. in EtOH group and 30 mg/kg TQ was administered i.p. in TQ1 and TQ2 groups. In addition, a total of 5 doses of 30 mg/kg TQ was injected i.p. 24, 48, 72 and 96 hours after the first dose in TQ2 group. Saline solution was given i.p. in the other groups. Blood samples were obtained for evaluating serum TBARS and BDNF levels. Results: The highest TBARS level was found in MeOH+MTx group and this increase was statistically significant as compared to control and Mtx groups (p<0.001) . A statistically significant reduction was detected in serum TBARS levels in MeOH+Mtx+EtOH, MeOH+Mtx+TQ1 and MeOH+Mtx+TQ2 groups (p<0.001). Maximum serum BDNF level elevation was found in MeOH+Mtx group and this increase was statistically significant as compared to control and Mtx groups (p<0.001). Serum BDNF levels were higher in MeOH+Mtx+EtOH, MeOH+Mtx+TQ1 and MeOH+Mtx+TQ2 groups and the difference was statistically significant (p<0.001). Conclusions: Thymoquinone could suppress proinflammation and lipid peroxidation in MeOH intoxication, lead to rapid toxicity adaptation, and play the role of neuroprotection more effectively than EtOH. These results may suggest that TQ could be used as an alternative treatment option in MeOH intoxication.

Neuroprotective effects of thymoquinone against MDMA-induced neurotoxicity

MDMA (3, 4-methylenedioxymethamphetamine) is a psychoactive substance that is associated with neurotoxicity. MDMA exposure to human results in the degeneration of neuronal cells in the hippocampus. Hence, the purpose of this study was to examine the potential of a natural compound known as thymoquinone (TQ) to protect against neuronal damage and memory impairment in rats stimulated by MDMA. The administration of TQ into MDMA-induced neuronal damage rats was carried out in male Sprague Dawley via a 1-week treatment dividing into four groups (n=36, 7-9 per group). The studied groups involved with the treatments comprise i) Control (1 mL/kg saline), ii) MDMA (10 mg/kg MDMA), iii) MDMA+TQ (10 mg/kg MDMA + 40 mg/kg TQ) and iv) TQ control (40 mg/kg TQ). A novel object recognition test (NORT) was carried out to evaluate the memory performance of the rats, followed by a histopathological assessment of the hippocampal dentate gyrus. The histopathology analysis revealed a significant increase in numbers of positive cells by Fluoro-Jade C following the effect of MDMA on neuronal damage (MDMA induced group) compared to control (P<0.05). Next, the TQ treatments observed in MDMA+TQ exhibited a decline in positive cells from Fluoro-Jade C. The index of recognition memory was found to be increased in MDMA+TQ compared to the MDMA alone (P<0.05). This study suggests that the neuronal damage inflicted by MDMA in a rat model has the potential to be treated by TQ.

Neuroprotective Effects of Thymoquinone by the Modulation of ER Stress and Apoptotic Pathway in In Vitro Model of Excitotoxicity.

Experimental evidence indicates that the activation of ionotropic glutamate receptors plays an important role in neurological disorders’ models such as epilepsy, cerebral ischemia and trauma. The glutamate receptor agonist kainic acid (KA) induces seizures and excitotoxic cell death in the CA3 region of the hippocampus. Thymoquinone (TQ) is the most important component of the essential oil obtained from black cumin (Nigella sativa L.) seeds. It has many pharmacological actions including antioxidant, anti-inflammatory, and anti-apoptotic effects. TQ was used in an in vitro experimental model of primary cultures where excitotoxicity was induced. Briefly, rat organotypic hippocampal slices were exposed to 5 µM KA for 24 h. Cell death in the CA3 subregions of slices was quantified by measuring propidium iodide fluorescence. The cross-talk between TQ, ER stress and apoptotic pathways was investigated by Western blot. In untreated slices TQ (10 µM) induced a significant increase on the PSD95 levels and it decreased the excitotoxic injury induced by KA. Additionally, TQ was able to ameliorate the KA-induced increase in unfolded proteins GRP78 and GRP94 expression. Finally, TQ was able to partially rescue the reduction of the KA-induced apoptotic pathway activation. Our results suggest that TQ modulates the processes leading to post-kainate neuronal death in the CA3 hippocampal area.

Thymoquinone Loaded Solid Lipid Nanoparticles Demonstrated Antidepressant-Like Activity in Rats via Indoleamine 2, 3- Dioxygenase Pathway.

The World Health Organization (WHO) has ranked depression the 4th leading cause of disability worldwide. Thymoquinone (TQ), is an active constituent of Nigella sativa having various medicinal properties but has poor solubility and bioavailability. This problem was overcome by developing nanoformulation of TQ. Previously TQ reported good antioxidant and anti-inflammatory effects. Recently TQ's anti-depressant effect was demonstrated. However, the mechanisms underlying the antidepressant effect of TQ still needs evaluation. Activation of Indoleamine-2,3-dioxygenase (IDO), (an enzyme that participates in the tryptophan metabolism), leads to a decrease of serotonin (5-HT) levels. The expression of this enzyme is associated with immune system activation, which has been proposed as a common mechanism that links depression. The present study was performed in stressed animals where hippocampal levels of pro-inflammatory cytokines (IL-6 and TNF α levels), brain derived neurotropic factor (BDNF) and hippocampal kynurenine (KYN), tryptophan (TRP) and serotonin (5-HT) levels were estimated. Treatment with TQ solid lipid nanoparticles (TQSLN 20 mg/kg p.o) and TQ suspension (20 mg/kg p.o) demonstrated antidepressant-like activity in chronic forced-swim stress model. Further, it reduced the elevated hippocampal IL-6 & TNFα and reversed the increased activity of IDO as measured by ratio of hippocampal KYN/TRP and 5HT/TRP in stressed rats. The results of the present study confirm anti-inflammatory and neuroprotective effects of TQ which may be associated with 5-HT pathway. Thus, the present study offers a newer approach to reduce symptoms of depression using TQSLN. Our results are preliminary, further research is needed for more conclusive view.

Thymoquinone as a Potential Neuroprotector in Acute and Chronic Forms of Cerebral Pathology.

Thymoquinone is one of the main active components of the essential oil from black cumin (Nigella sativa) seeds. Thymoquinone exhibits a wide range of pharmacological activities, including neuroprotective action demonstrated in the models of brain ischemia/reperfusion, Alzheimer's and Parkinson's diseases, and traumatic brain injury. The neuroprotective effect of thymoquinone is mediated via inhibition of lipid peroxidation, downregulation of proinflammatory cytokines, maintenance of mitochondrial membrane potential, and prevention of apoptosis through inhibition of caspases-3, -8, and -9. Thymoquinone-based mitochondria-targeted antioxidants are accumulated in the mitochondria and exhibit neuroprotective properties in nanomolar concentrations. Thymoquinone reduces the negative effects of acute and chronic forms of brain pathologies. The mechanisms of the pharmacological action of thymoquinone and its chemical derivatives require more comprehensive studying. In this paper, we formulated the prospects of application of thymoquinone and thymoquinone-based drugs in the therapy of neurodegenerative diseases.

Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI.

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism.

Neuroprotective Effects of Thymoquinone in Acrylamide-Induced Peripheral Nervous System Toxicity Through MAPKinase and Apoptosis Pathways in Rat.

Acrylamide (ACR) is extensively used in industrial areas and has been demonstrated to induce neurotoxicity via oxidative stress and apoptosis. In this study, we assessed the probable protective effects of thymoquinone (TQ), an active constituent of Nigella sativa, against ACR-induced neurotoxicity. ACR (50mg/kg, i.p., for 11 days) and TQ (2.5, 5 and 10mg/kg, i.p., for 11 days) were administered to rats. On 12th day, gait score was examined and rats were sacrificed. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were determined in sciatic nerve. Furthermore, western blotting was conducted. The exposure of rats to ACR caused severe gait disabilities. The MDA and GSH contents were increased and decreased, respectively. ACR decreased P-ERK/ERK ratio and myelin basic protein (MBP) content, but significantly increased P-JNK/JNK, P-P38/P38, Bax/Bcl-2 ratios and caspase 3 and 9 levels. Concurrently administration of TQ (5 and 10mg/kg) with ACR, prevented gait abnormalities and meaningfully reduced MDA and elevated the GSH contents. Furthermore, TQ (5mg/kg) elevated the P-ERK/ERK ratio and MBP content while reduced the P-JNK/JNK, P-P38/P38 ratios and apoptotic markers. MAP kinase and apoptosis signaling pathways were involved in ACR-induced neurotoxicity in rat sciatic nerve and TQ significantly reduced ACR neurotoxicity. TQ afforded neuroprotection, in part, due to its anti-oxidative stress and anti-apoptotic mechanisms.

The Neuroprotective Effects of Thymoquinone: A Review.

Thymoquinone (TQ), one of the main components active of Nigella sativa, exhibited very useful biomedical effects such as anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects. There are several studies about pharmacological activities of TQ but its neuroprotection effects are not fully described. The literature search has indicated many studies pertaining to the effects of TQ in neurological problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and memory, and so on. In addition, TQ protected brain cells from various injuries due to its antioxidant, anti-inflammatory, and apoptotic effects in cell line and experimental animal models. The present study has been designed to review the scientific literature about the pharmacological activities of TQ to the neurological diseases. This study purposed that although experimental studies indicated the beneficial effects of TQ against nervous system problems, better designed clinical trials in humans are needed to confirm these effects.

Neuroprotective effects of thymoquinone against cerebellar histopathological changes in propylthiouracilinduced hypothyroidism in adult rats

Purpose: To evaluate the effects of thymoquinone (TQ) on histological and immunohistochemical changes in the cerebellar cortex induced by propylthiouracil (PTU) treatment in rats.Methods: Thirty-two adult male albino rats were randomly divided into four groups: C, control; PTU, treatment with oral PTU to induce hypothyroidism; TQ, treatment with TQ; and PTU + TQ, concomitant treatment with oral PTU and TQ for 6 weeks. Cavalieri’s principle and physical dissector methods were employed for unbiased deduction of cerebellar granular layer volume, numerical density, and number of granular cells.Results: In the PTU group, hematoxylin and eosin (H&E)-stained sections revealed degeneration of Purkinje cells, neuronal loss, and spongiosis in the white matter. A decrease in the number of astrocytes-expressing glial fibrillary acidic protein (GFAP) and a significant decrease in granular layer cell density were also seen. Concomitant administration of TQ ameliorated histopathological changes, increased the proportion of GFAP-positive astrocytes, increased granular cell density, and significantly (p < 0.05) increased the levels of thyroid-stimulating hormones, T3 and T4.Conclusion: TQ treatment significantly decreases cerebellar changes resulting from PTU-induced hypothyroidism, and results in the retention of neuronal structural integrity in the cerebellar cortex.Keywords: Hypothyroidism, Cerebellum, Thymoquinone, Stereology, Glial fibrillary acidic protein, Neuronal structural integrity

The histopathological and electrophysiological effects of thymoquinone and methylprednisolone in a rabbit traumatic facial nerve paralysis model

ObjectiveWe aimed to determine the effects of methylprednisolone and thymoquinone on nerve healing in a traumatic facial nerve paralysis animal model. Subjects and methodsTwenty-four rabbits were randomly divided into 4 groups: group I: control group received no medication and no trauma; group II: sham group received no medication after facial nerve trauma group III: 5mg/kg/day thymoquinone administered; group IV: 1mg/kg/day methylprednisolone administered. An initial electrophysiological assessment was performed in all the animals. The buccal branch of the facial nerve was then clipped to form a traumatic facial paralysis model. The drugs were administered for two weeks once a day. At the end of the second month, the electrophysiological assessments were performed and the distal part of the traumatic facial nerve were dissected and examined under light microscopy. ResultsBest nerve regeneration was observed in the control and the thymoquinone groups, respectively, whereas the weakest regeneration was determined in the sham group. Thymoquinone and methylprednisolone significantly increased nerve recovery, as measured by histopathological scores and electrophysiological assessment. In the thymoquinone group, due to postoperative amplitude, axon diameter and thickness of myelin sheath values were significantly further increased nerve regeneration compared to that of the methylprednisolone group and these values were close to those of the values of the control group. ConclusionThymoquinone was slightly better than methylprednisolone for functional nerve recovery. The neuroprotective effect of thymoquinone was attributed to its antioxidant and anti-inflammatory effects. Thymoquinone can have a new treatment option to ameliorate the nerve injury.

Neuroprotective Effects of Thymoquinone in Aβ1–42‐induced Toxicity in SK‐N‐SH Neuronal Cells

Neuroprotective Effects of Thymoquinone in Aβ_1–42‐induced Toxicity in SK‐N‐SH Neuronal Cells

Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis.

OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the spinal cord.

Neuroprotective effect of thymoquinone in acrylamide-induced neurotoxicity in Wistar rats.

Acrylamide (ACR) has broad applications in different industries. It also forms in food during heating process. Oxidative stress has a critical role in ACR-induced neurotoxicity in both in vitro and in vivo models; therefore, the aim of the current study was the evaluation of effects of thymoquinone, the main constituent of volatile oil from Nigella sativa seeds in ACR-induced neurotoxicity. Male Wistar rats were treated with ACR (50 mg/kg IP) alone or with thymoquinone (TQ) (2.5, 5, 10 mg/kg IP) for 11 days. Two protocols were used in this study, A: in this one TQ and ACR were used simultaneously, B: Administration of TQ was started 1 week before ACR treatment and continued during exposure to ACR. At the end of the treatment, behavioral index (gait score) was examined for rats. After that, rats were sacrificed and molondialdehyde (MDA) as a marker of lipid peroxidation and glutathione (GSH) content were determined in cerebral cortex. Exposure to ACR led to severe gait abnormalities and treatment with TQ significantly decreased abnormalities. Level of MDA was elevated in cerebral cortex after exposure to ACR while TQ treatment significantly and in a dose-dependent manner reduced lipid peroxidation. Results clearly showed that there is no significant difference between two protocols of administration of TQ. It suggests the neuroprotective effect of TQ in this model in part, may be because of due the antioxidant activity of this natural compound.

Thymoquinone and vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABAB1 receptor in adult rats cortex and hippocampus.

Epilepsy is a common neurological disorder that leads to neuronal excitability and provoke various forms of cellular reorganization in the brain. In this study, we investigate the anti-convulsant and neuroprotective effects of thymoquinone (TQ) and vitamin C against pentylenetetrazole (PTZ)-induced generalized seizures. Epileptic seizures were induced in adult rats using systemic intraperitoneal injections of PTZ (50mg/kg) for 7days. Animals pretreated with either TQ or vitamin C or in combination attenuated PTZ-induced seizures and mortality in rats as well neurodegeneration in the cells. Compared to PTZ, TQ and vitamin C significantly prolonged the onset of seizures (p>0.05) as well decrease the high-grade seizures. Analysis of electroencephalogram (EEG) recordings revealed that TQ or vitamin C supplementation significantly reduced polyspike and epileptiform discharges. Epileptic seizures caused a decline in expression of gamma-aminobutyric acid B1 receptor (GABAB1R) (p>0.05), unchanged expression of protein kinase A (PKA), decreased calcium/calmodulin-dependent protein kinase II (CaMKII) (p>0.05) and inhibit the phosphorylation of cAMP response element-binding protein (CREB) (p>0.05) in cortex and hippocampus, respectively, compared with control. Changes in expression of GABAB1R, CaMKII and CREB by PTZ were reversed by TQ and vitamin C supplementation. Moreover, PTZ significantly increased Bax, decreased Bcl-2 expression and finally the activation of caspase-3. TQ and vitamin C pretreatment reversed all these deleterious effects induced by PTZ. TQ and vitamin C showed anticonvulsant effects via activation of GABAB1R/CaMKII/CREB pathway and suggest a potential therapeutic role in epilepsy.

P078: Neuroprotective effect of thymoquinone against lipopolysaccharide-induced Alzheimer's disease in an animal model

P078: Neuroprotective effect of thymoquinone against lipopolysaccharide-induced Alzheimer's disease in an animal model

Neuroprotective Effect of Thymoquinone on Repeated Immobilization Stress-Induced Oxidative Stress in Rats

The present study was designed to investigate the effect of Thymoquinone (TQ) in restraint stress- induced biochemical alterations in Wistar albino rats. Restraint stress was applied for 21 days (4 h/day) and 60 min before every stress exposure the rats were treated with two doses of TQ (5 and 10 mg/kg). In serum, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Interleukin-1β (IL-1β) Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) were estimated. Thiobarbituric Acid Reactive Substances (TBARS), reduced Glutathione (GSH), nitrite and nitrate levels and Super Oxide Dismutase (SOD), Catalase (CAT), Glutathione-S-Transferase (GST), Glutathione-Reductase (GR) and Glutathione Peroxidase (GSH-Px) activities were estimated in brain. Interleukins and enzymatic activities in serum significantly elevated by the restraint stress and were ameliorated by both the doses of TQ treatment. In brain TBARS, nitrite and nitrate levels significantly elevated due to restraint stress, the TQ treatment brings back to normal levels. Restraint stress significantly decreased in oxidative enzyme activities as the SOD, CAT, GST, GSH-Px and GR. TQ treatments significantly enhanced the activities compared to untreated stressed rats. Present results revealed that, TQ reduced the restraint stress-induced oxidative process in terms of above mentioned biochemical parameters. Thus, in view of its antioxidative nature, TQ may be developed as an effective therapeutic agent for stress-induced oxidation and CNS depression.