Thymoquinone protects cultured rat primary neurons against amyloid β-induced neurotoxicity

Alhebshi, A.H.; Gotoh, Masao; Suzuki, I.

doi:10.1016/j.bbrc.2012.11.139

Cited by 111 publications

(72 citation statements)

References 30 publications

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“…In addition, NSO treatment of STZ-diabetic rats decreased significantly the level of Aβ-42 (7-fold), these results in agreement with what was reported before [50] that TQ has neuro-protection potential against Aβ-42 in rat hippocampal and cortical neurons and thus it might be considered as a promising candidate for AD treatment. It is contradictory to what has been suggested that MT alone increased the production of beta amyloid and enhanced the chances of AD [51].…”

Section: Discussionsupporting

confidence: 91%

Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs

2017

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Background and objectivesInsulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer’s progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated.MethodsT2DM-induced rats were orally and daily administrated 2.0 ml NSO, 100 mg metformin (MT), 0.8 mg glimepiride (GI) and different combinations (100 mg MT & 2.0 ml NSO, 0.8 mg GI & 2.0 ml NSO and 2.0 ml NSO & intraperitoneal injection of 1/100 LD50 of IOMe-AG538) per kg body weight for 21 days.ResultsA significant increase in the brain lipid peroxidation and decrease in the antioxidant status with peripheral and central production of pro-inflammatory mediators were observed in diabetes-induced rats. The brain AChE was activated and associated with diminished brain glucose level and cholinergic function. In addition, the brain insulin resistance and the attenuated insulin signaling pathway (p-IRS/ p-AKT/p-GSK-3β) were accompanied by an augmentation in GSK-3β level, which in turn may contribute in the extensive alterations of Tau phosphorylation along with changes in PP2A level. Furthermore, neuronal loss and elevation in Aβ-42 plaque formation were observed due to a low IDE formation and an increased expression of p53, BACE1 and APP with diminished ADAM10, SIRT1 and BDNF levels. The expression profile of AD-related miRNAs in sera and brain tissues displayed its neuro-protection role. The treatment of diabetes-induced rats with NSO and the anti-diabetic drugs alone and/or in combination have the potential to suppress the oxidative stress, the pro-inflammatory mediators and amyloidogenic pathway. Moreover, it lowers the insulin receptor inhibitory effect of IOMe-AG538 and modifies the insulin-signaling pathway. Therefore, it prevents the neurotoxicity, amyloid plaque formation and Tau hyper-phosphorylation and restores AD-related miRNA normal levels.ConclusionThese data suggest that NSO or its combined treatments with anti-diabetic drugs have a possible benefit as disease modifying agents for the insulin resistance in the brain through enhancing brain insulin signaling pathway.

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Section: Discussionsupporting

confidence: 91%

Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs

2017

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“…Likewise, the anti-inflammatory properties of TQ treatment have been demonstrated in mast cells, microglia, kidney, and liver (El Gazzar et al, 2007; Al-Malki and Sayed, 2014; Mahmoud et al, 2014; Taka et al, 2015). Furthermore, studies have also indicated that TQ treatment provides neuroprotection against amyloid β-induced and α-synuclein-induced neurotoxicity (Khan et al, 2012, Alhebshi et al, 2013, Alhebshi et al, 2014), traumatic brain injury (Gülşen et al, 2016), environmental neurotoxins (Kanter, 2008; Radad et al, 2009; Radad et al, 2014), and transient forebrain ischemia (Al-Majed et al, 2006). Many studies have also indicated that TQ's protective effects involve the modulation of the NFκB pathway (Mohamed et al, 2005, El Gazzar et al, 2007, Sayed and Morcos, 2007, Sethi et al, 2008, Al-Malki and Sayed, 2014).…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells

Cobourne-Duval

Taka

Mendonca

et al. 2018

Journal of Neuroimmunology

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Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil. TQ has been shown to exhibit anti-inflammatory, anti-oxidative, and neuroprotective effects. In this study, lipopolysaccharide (LPS) and interferon gamma (IFNγ) activated BV-2 microglial cells were treated with TQ (12.5 μM for 24 h). We performed quantitative proteomic analysis using Orbitrap/Q-Exactive Proteomic LC-MS/ MS (Liquid chromatography-mass spectrometry) to globally assess changes in protein expression between the treatment groups. Furthermore, we evaluated the ability of TQ to suppress the inflammatory response using ELISArray™ for Inflammatory Cytokines. We also assessed TQ's effect on the gene expression of NFκB signaling targets by profiling 84 key genes via real-time reverse transcription (RT2) PCR array. Our results indicated that TQ treatment of LPS/IFNγ-activated microglial cells significantly increased the expression of 4 antioxidant, neuroprotective proteins: glutaredoxin-3 (21 fold; p < 0.001), biliverdin reductase A (15 fold; p < 0.0001), 3-mercaptopyruvate sulfurtransferase (11 fold; p < 0.01), and mitochondrial lon protease (> 8 fold; p < 0.001) compared to the untreated, activated cells. Furthermore, TQ treatment significantly (P < 0.0001) reduced the expression of inflammatory cytokines, IL-2 = 38%, IL-4 = 19%, IL-6 = 83%, IL-10 = 237%, and IL-17a = 29%, in the activated microglia compared to the untreated, activated which expression levels were significantly elevated compared to the control microglia: IL-2 = 127%, IL-4 = 151%, IL-6 = 670%, IL-10 = 133%, IL-17a = 127%. Upon assessing the gene expression of NFκB signaling targets, this study also demonstrated that TQ treatment of activated microglia resulted in > 7 fold down-regulation of several NFκB signaling targets genes, including interleukin 6 (IL6), complement factor B (CFB), chemokine (C–C motif) ligand 3 (CXCL3), chemokine (C–C) motif ligand 5 (CCL5) compared to the untreated, activated microglia. This modulation in gene expression counteracts the > 10-fold upregulation of these same genes observed in the activated microglia compared to the controls. Our results show that TQ treatment of LPS/IFNγ-activated BV-2 microglial cells induce a significant increase in expression of neuroprotective proteins, a significant decrease in expression inflammatory cytokines, and a decrease in the expression of signaling target genes of the NFκB pathway. Our findings are the first to show that TQ treatment increased the expression of these neuroprotective proteins (biliverdin reductase-A, 3-mercaptopyruvate sulfu...

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“…Also, Nigella sativa oil and its active ingredient TQ, protects brain tissue against radiation-induced nitrosative stress 14. The TQ has a protective potential in the rat hippocampus and cortical neurons against Abb1-42 and thus, it may be a promising agent for the treatment of Alzheimer’s disease 15. A limited number of studies also reported that TQ has shown antiepileptic effects.…”

mentioning

confidence: 99%

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

Beyazçiçek

Ankaralı

Beyazçiçek

et al. 2016

NSJ

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Objective:To investigate the effects of thymoquinone (TQ) in a penicillin-induced epilepsy model in rats.Methods:This experimental study included 56 adult male Wistar rats. Experiments were performed in the Research Laboratory of the Department of Physiology, Medical School, Duzce University, Duzce, Turkey, between October 2013 and December 2014. Animals were divided into the following 7 groups: sham, control, only thymoquinone, vehicle (Dimethylsulfoxide), and doses of 10, 50, and 100 mg/kg of TQ. After rats were anesthetized, the left part of the skull was removed. A pair of silver/silver chloride electrodes was placed on the somatomotor area, and electrocorticographic recording was started. After 5 minutes basal activity was recorded, and TQ was applied intraperitoneally. At the thirtieth minute after TQ, epileptiform activity was induced by intracortical penicillin. The first spike latency, spike frequency, and the amplitude of epileptiform activity were analyzed statistically.Results:The different doses of TQ significantly increased the latency time to onset of first spike wave, and decreased the frequency, and amplitude of epileptiform activity in the first 20 minutes compared with the control group.Conclusion:Thymoquinone shows potential as an antiepileptic drug resulting from its effects of prolonged latency time, and reduced spike wave frequency and amplitude of epileptiform activity.

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Thymoquinone protects cultured rat primary neurons against amyloid β-induced neurotoxicity

Cited by 111 publications

References 30 publications

Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs

Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs

Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells

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

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