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Mahmoud N Nagi - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effects of Thymoquinone against transient forebrain ischemia in the rat hippocampus
European Journal of Pharmacology, 2006Co-Authors: Abdulhakeem A Almajed, Fadhel A Alomar, Mahmoud N NagiAbstract:Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of Thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, Thymoquinone and ischemia+Thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia-reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia-reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of Thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in Thymoquinone-treated versus 77% for ischemia, P<0.001), which confirm the protective role of Thymoquinone in ischemia-reperfusion injury. Also, pretreatment of ischemic rats with Thymoquinone decreased the elevated levels of malondialdehyde and increased GSH contents, catalase and SOD activities to normal levels. Thymoquinone and thymohydroquinone inhibited the in vitro non-enzymatic lipid peroxidation in hippocampal homogenate induced by iron-ascorbate. The IC50 for Thymoquinone and thymohydroquinone were found to be 12 and 3 microM respectively. This suggests that the protection of Thymoquinone and its metabolite involve increased resistance to oxidative stress. In conclusion, Thymoquinone is effective in protecting rats against transient forebrain ischemia-induced damage in the rat hippocampus. This spectacular protection makes Thymoquinone a promising agent in pathologies implicating neurodegenaration such as cerebral ischemia.
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Neuroprotective effects of Thymoquinone against transient forebrain ischemia in the rat hippocampus.
European Journal of Pharmacology, 2006Co-Authors: Abdulhakeem A. Al-majed, Fadhel A. Al-omar, Mahmoud N NagiAbstract:Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of Thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, Thymoquinone and ischemia+Thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia-reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia-reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of Thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in Thymoquinone-treated versus 77% for ischemia, P
Abdulhakeem A Almajed - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effects of Thymoquinone against transient forebrain ischemia in the rat hippocampus
European Journal of Pharmacology, 2006Co-Authors: Abdulhakeem A Almajed, Fadhel A Alomar, Mahmoud N NagiAbstract:Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of Thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, Thymoquinone and ischemia+Thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia-reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia-reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of Thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in Thymoquinone-treated versus 77% for ischemia, P<0.001), which confirm the protective role of Thymoquinone in ischemia-reperfusion injury. Also, pretreatment of ischemic rats with Thymoquinone decreased the elevated levels of malondialdehyde and increased GSH contents, catalase and SOD activities to normal levels. Thymoquinone and thymohydroquinone inhibited the in vitro non-enzymatic lipid peroxidation in hippocampal homogenate induced by iron-ascorbate. The IC50 for Thymoquinone and thymohydroquinone were found to be 12 and 3 microM respectively. This suggests that the protection of Thymoquinone and its metabolite involve increased resistance to oxidative stress. In conclusion, Thymoquinone is effective in protecting rats against transient forebrain ischemia-induced damage in the rat hippocampus. This spectacular protection makes Thymoquinone a promising agent in pathologies implicating neurodegenaration such as cerebral ischemia.
Abdulhakeem A. Al-majed - One of the best experts on this subject based on the ideXlab platform.
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Neuroprotective effects of Thymoquinone against transient forebrain ischemia in the rat hippocampus.
European Journal of Pharmacology, 2006Co-Authors: Abdulhakeem A. Al-majed, Fadhel A. Al-omar, Mahmoud N NagiAbstract:Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of Thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, Thymoquinone and ischemia+Thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia-reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia-reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of Thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in Thymoquinone-treated versus 77% for ischemia, P
Olumayokun A Olajide - One of the best experts on this subject based on the ideXlab platform.
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inhibition of neuroinflammation by Thymoquinone requires activation of nrf2 are signalling
International Immunopharmacology, 2017Co-Authors: Ravikanth Velagapudi, Izabela Lepiarz, Asit Kumar, Harsharan S. Bhatia, Bernd L. Fiebich, Abdelmeneim Elbakoush, Olumayokun A OlajideAbstract:Thymoquinone is an antioxidant phytochemical that has been shown to inhibit neuroinflammation. However, little is known about the potential roles of intracellular antioxidant signalling pathways in its anti-inflammatory activity. The objective of this study was to elucidate the roles played by activation of the Nrf2/ARE antioxidant mechanisms in the anti-inflammatory activity of this compound. Thymoquinone inhibited lipopolysaccharide (LPS)-induced neuroinflammation through interference with NF-κB signalling in BV2 microglia. Thymoquinone also activated Nrf2/ARE signalling by increasing nuclear localisation, DNA binding and transcriptional activity of Nrf2, as well as increasing protein levels of HO-1 and NQO1. Suppression of Nrf2 activity through siRNA or with the use of trigonelline resulted in the loss of anti-inflammatory activity by Thymoquinone. Taken together, our studies show that Thymoquinone inhibits NF-κB-dependent neuroinflammation in BV2 microglia, by targeting antioxidant pathway involving activation of both Nrf2/ARE. We propose that activation of Nrf2/ARE signalling pathway by Thymoquinone probably results in inhibition of NF-κB-mediated neuroinflammation.
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AMPK and SIRT1 activation contribute to inhibition of neuroinflammation by Thymoquinone in BV2 microglia.
Molecular and cellular biochemistry, 2017Co-Authors: Ravikanth Velagapudi, Abdelmeneim El-bakoush, Izabela Lepiarz, Folashade Ogunrinade, Olumayokun A OlajideAbstract:Thymoquinone is a known inhibitor of neuroinflammation. However, the mechanism(s) involved in its action remain largely unknown. In this study, we investigated the roles of cellular reactive oxygen species (ROS), 5' AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) in the anti-neuroinflammatory activity of Thymoquinone. We investigated effects of the compound on ROS generation in LPS-activated microglia using the fluorescent 2',7'-dichlorofluorescin diacetate (DCFDA)-cellular ROS detection. Immunoblotting was used to detect protein levels of p40phox, gp91phox, AMPK, LKB1 and SIRT1. Additionally, ELISA and immunofluorescence were used to detect nuclear accumulation of SIRT1. NAD+/NADH assay was also performed. The roles of AMPK and SIRT1 in anti-inflammatory activity of Thymoquinone were investigated using RNAi and pharmacological inhibition. Our results show that Thymoquinone reduced cellular ROS generation, possibly through inhibition of p40phox and gp91phox protein. Treatment of BV2 microglia with Thymoquinone also resulted in elevation in the levels of LKB1 and phospho-AMPK proteins. We further observed that Thymoquinone reduced cytoplasmic levels and increased nuclear accumulation of SIRT1 protein and increased levels of NAD+. Results also show that the anti-inflammatory activity of Thymoquinone was abolished when the expressions of AMPK and SIRT1 were suppressed by RNAi or pharmacological antagonists. Pharmacological antagonism of AMPK reversed Thymoquinone-induced increase in SIRT1. Taken together, we propose that Thymoquinone inhibits cellular ROS generation in LPS-activated BV2 microglia. It is also suggested that activation of both AMPK and NAD+/SIRT1 may contribute to the anti-inflammatory, but not antioxidant activity of the compound in BV2 microglia.
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Inhibition of neuroinflammation by Thymoquinone requires activation of Nrf2/ARE signalling.
International immunopharmacology, 2017Co-Authors: Ravikanth Velagapudi, Abdelmeneim El-bakoush, Izabela Lepiarz, Asit Kumar, Harsharan S. Bhatia, Bernd L. Fiebich, Olumayokun A OlajideAbstract:Thymoquinone is an antioxidant phytochemical that has been shown to inhibit neuroinflammation. However, little is known about the potential roles of intracellular antioxidant signalling pathways in its anti-inflammatory activity. The objective of this study was to elucidate the roles played by activation of the Nrf2/ARE antioxidant mechanisms in the anti-inflammatory activity of this compound. Thymoquinone inhibited lipopolysaccharide (LPS)-induced neuroinflammation through interference with NF-κB signalling in BV2 microglia. Thymoquinone also activated Nrf2/ARE signalling by increasing nuclear localisation, DNA binding and transcriptional activity of Nrf2, as well as increasing protein levels of HO-1 and NQO1. Suppression of Nrf2 activity through siRNA or with the use of trigonelline resulted in the loss of anti-inflammatory activity by Thymoquinone. Taken together, our studies show that Thymoquinone inhibits NF-κB-dependent neuroinflammation in BV2 microglia, by targeting antioxidant pathway involving activation of both Nrf2/ARE. We propose that activation of Nrf2/ARE signalling pathway by Thymoquinone probably results in inhibition of NF-κB-mediated neuroinflammation.
Hiroshi Watanabe - One of the best experts on this subject based on the ideXlab platform.
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antinociceptive effects of nigella sativa oil and its major component Thymoquinone in mice
European Journal of Pharmacology, 2000Co-Authors: Abdelfattah Mohamed Abdelfattah, Kinzo Matsumoto, Hiroshi WatanabeAbstract:Abstract The antinociceptive effects of Nigella sativa oil and its major component, Thymoquinone, were examined in mice. The p.o. administration of N. sativa oil (50–400 mg/kg) dose-dependently suppressed the nociceptive response in the hot-plate test, tail-pinch test, acetic acid-induced writhing test and in the early phase of the formalin test. The systemic administration (2.5–10 mg/kg, p.o. and 1–6 mg/kg, i.p.) and the i.c.v. injection (1–4 μg/mouse) of Thymoquinone attenuated the nociceptive response in not only the early phase but also the late phase of the formalin test. Naloxone injected s.c. (1 mg/kg) significantly blocked N. sativa oil- and Thymoquinone-induced antinociception in the early phase of the formalin test. Moreover, the i.c.v. injection of naloxone (10 μg/mouse), the μ1-opioid receptor antagonist, naloxonazine (1–5 μg/mouse), or the κ-opioid receptor antagonist, nor-binaltorphimine (1–5 μg/mouse), significantly reversed Thymoquinone-induced antinociception in the early phase but not the late phase of the formalin test, whereas the δ-opioid receptor antagonist, naltrindole (1–5 ng/mouse, i.c.v.), had no effect on either phase. The antinociceptive effect of morphine was significantly reduced in Thymoquinone- and N. sativa oil-tolerant mice, but not vice versa. These results suggest that N. sativa oil and Thymoquinone produce antinociceptive effects through indirect activation of the supraspinal μ1- and κ-opioid receptor subtypes.
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antinociceptive effects of nigella sativa oil and its major component Thymoquinone in mice
European Journal of Pharmacology, 2000Co-Authors: Abdelfattah Mohamed Abdelfattah, Kinzo Matsumoto, Hiroshi WatanabeAbstract:The antinociceptive effects of Nigella sativa oil and its major component, Thymoquinone, were examined in mice. The p.o. administration of N. sativa oil (50-400 mg/kg) dose-dependently suppressed the nociceptive response in the hot-plate test, tail-pinch test, acetic acid-induced writhing test and in the early phase of the formalin test. The systemic administration (2.5-10 mg/kg, p.o. and 1-6 mg/kg, i.p.) and the i.c.v. injection (1-4 microgram/mouse) of Thymoquinone attenuated the nociceptive response in not only the early phase but also the late phase of the formalin test. Naloxone injected s.c. (1 mg/kg) significantly blocked N. sativa oil- and Thymoquinone-induced antinociception in the early phase of the formalin test. Moreover, the i.c.v. injection of naloxone (10 microgram/mouse), the mu(1)-opioid receptor antagonist, naloxonazine (1-5 microgram/mouse), or the kappa-opioid receptor antagonist, nor-binaltorphimine (1-5 microgram/mouse), significantly reversed Thymoquinone-induced antinociception in the early phase but not the late phase of the formalin test, whereas the delta-opioid receptor antagonist, naltrindole (1-5 ng/mouse, i.c.v.), had no effect on either phase. The antinociceptive effect of morphine was significantly reduced in Thymoquinone- and N. sativa oil-tolerant mice, but not vice versa. These results suggest that N. sativa oil and Thymoquinone produce antinociceptive effects through indirect activation of the supraspinal mu(1)- and kappa-opioid receptor subtypes.
