Nrf2 activation https://greenmedinfo.com/category/keywords/Nrf2%20activation en A leaf extract of Dandelion and its main compound activated nuclear factor erythroid 2-related factor 2 and induced heme oxygenase 1. https://greenmedinfo.com/article/leaf-extract-dandelion-and-its-main-compound-activated-nuclear-factor-erythroi n/a PMID:  J Med Food. 2016 Dec 27. Epub 2016 Dec 27. PMID: 28026992 Abstract Title:  Sesquiterpene Lactone Composition and Cellular Nrf2 Induction of Taraxacum officinale Leaves and Roots and Taraxinic Acidβ-d-Glucopyranosyl Ester. Abstract:  Taraxacum officinale, the common dandelion, is a plant of the Asteraceae family, which is used as a food and medical herb. Various secondary plant metabolites such as sesquiterpene lactones, triterpenoids, flavonoids, phenolic acids, coumarins, and steroids have been described to be present in T. officinale. Dandelion may exhibit various health benefits, including antioxidant, anti-inflammatory, and anticarcinogenic properties. We analyzed the leaves and roots of the common dandelion (T. officinale) using high-performance liquid chromatography/mass spectrometry to determine its sesquiterpene lactone composition. The main compound of the leaf extract taraxinic acidβ-d-glucopyranosyl ester (1), a sesquiterpene lactone, was isolated and the structure elucidation was conducted by nuclear magnetic resonance spectrometry. The leaf extract and its main compound 1 activated the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in human hepatocytes more significantly than the root extract. Furthermore, the leaf extract induced the Nrf2 target gene heme oxygenase 1. Overall, present data suggest that compound 1 may be one of the active principles of T. officinale. https://greenmedinfo.com/article/leaf-extract-dandelion-and-its-main-compound-activated-nuclear-factor-erythroi#comments Dandelion Oxidative Stress Antioxidants Heme oxygenase-1 inducer Nrf2 activation Antioxidants Dandelion Heme oxygenase-1 inducer Nrf2 activation oxidative stress Plant Extracts In Vitro Study Tue, 03 Jan 2017 00:16:53 +0000 greenmedinfo 141323 at https://greenmedinfo.com Adlay is a potential chemopreventive TCM to block multistage carcinogenesis with anti-initiation, promotion and progression properties. https://greenmedinfo.com/article/adlay-potential-chemopreventive-tcm-block-multistage-carcinogenesis-anti-initi n/a PMID:  J Tradit Complement Med. 2012 Oct ;2(4):267-75. PMID: 24716141 Abstract Title:  Adlay ( yì yĭ;&quot;soft-shelled job&#039;s tears&quot;; the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a Potential Cancer Chemopreventive Agent toward Multistage Carcinogenesis Processes. Abstract:  Adlay ( yì yĭ&quot;soft-shelled job&#039;s tears&quot;, the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop that has long been used in traditional Chinese medicine (TCM) and as a nourishing food in China for the treatment of warts, chapped skin, rheumatism, neuralgia, inflammatory, and neoplastic diseases. In addition, adlay also has been said to have stomachic, diuretic, antipholgistic, anodynic, and antispasmodic effects. Carcinogenesis is a multistage process that begins with exposure of viruses or chemicals that are found in the environment. Chemoprevention refers to the use of natural or synthetic, non-toxic chemical substances to reverse, repress, or prevent carcinogenesis. In this review, we summarize recent research attempting to study the chemopreventive blocking and suppressing potential of adlay and its active components in scavenging electrophiles and reactive oxygen species, antimutagenicity, enhancing Nrf2-mediated detoxification and antioxidant effect, altering carcinogen metabolism, suppressing proliferation, decreasing inflammation, and enhancing antitumor immunity. In addition, several active components with diverse chemopreventive properties have been also mentioned in this review article. https://greenmedinfo.com/article/adlay-potential-chemopreventive-tcm-block-multistage-carcinogenesis-anti-initi#comments Adlay Cancers: All Antioxidants Antiproliferative Chemopreventive Nrf2 activation Adlay Antioxidants Antiproliferative Cancers: All Chemopreventive Nrf2 activation Review Fri, 20 Apr 2018 23:32:17 +0000 greenmedinfo 163099 at https://greenmedinfo.com Allicin provides protection against arsenic trioxide induced liver injury. https://greenmedinfo.com/article/allicin-provides-protection-against-arsenic-trioxide-induced-liver-injury n/a PMID:  Biol Trace Elem Res. 2017 Mar ;176(1):192-200. Epub 2016 Aug 25. PMID: 27561292 Abstract Title:  Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats. Abstract:  Arsenic trioxide (As2O3) is both the most prevalent, naturally occurring inorganic arsenical threatening human health and an efficient therapeutic for acute promyelocytic leukemia. Regretfully, As2O3-treated cancer patients often suffer from hepatotoxicity. While effective antioxidant and anticarcinogenic actions of allicin have previously been demonstrated, studies indicating how allicin affects As2O3-induced hepatotoxicity and arsenic accumulation are lacking. Our study, for the first time, elaborates potential details of the hepatoprotective mechanisms of allicin against As2O3-induced liver injury. Wistar rats were administrated allicin (30 mg/kg) 1 h before As2O3 (3 mg/kg) by daily gavage for 2 weeks. Our results indicate that allicin ameliorated As2O3-induced liver dysfunction, oxidative stress, and arsenic accumulation in the liver. Meanwhile, allicin decreased NF-κB level and upregulated expression of proteins reduced by As2O3 including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1, and Krüppel-like factor 9 (KLF9). In addition, allicin promoted B cell lymphoma-extra large expression and suppressed B cell lymphoma-2-associatedX protein levels regulated by As2O3. However, neither allicin nor As2O3 affected cytochrome P450 2E1 mRNA expression. In conclusion, allicin attenuated As2O3-induced hepatotoxicity by activating the Nrf2 signaling pathway involving KLF9 to inhibit oxidative stress and apoptosis. Our findings elucidate a detailed mechanism by which allicin provides protection against As2O3-induced liver injury and support its potential role as an adjunctive therapy for patients suffering from chronic arsenic exposure. https://greenmedinfo.com/article/allicin-provides-protection-against-arsenic-trioxide-induced-liver-injury#comments Allicin Arsenic Poisoning Oxidative Stress Antioxidants Arsenic Trioxide NF-kappaB Inhibitor Nrf2 activation Allicin Antioxidants Arsenic Poisoning NF-kappaB Inhibitor Nrf2 activation oxidative stress Animal Study Thu, 07 Sep 2017 23:00:33 +0000 greenmedinfo 152926 at https://greenmedinfo.com Astaxanthin promotes Nrf2/ARE signalling to inhibit high glucose induced renal fibrosis in GMCs. https://greenmedinfo.com/article/astaxanthin-promotes-nrf2are-signalling-inhibit-high-glucose-induced-renal-fib n/a PMID:  Mar Drugs. 2018 Apr 5 ;16(4). Epub 2018 Apr 5. PMID: 29621130 Abstract Title:  Astaxanthin Promotes Nrf2/ARE Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs. Abstract:  Oxidative stress is the main cause of diabetic nephropathy (DN) progression. Nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling is a crucial cellular defense system to cope with oxidative stress. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid with remarkable antioxidative capacity. AST exerted renal protective in diabetic rats. This study aimed to determine whether AST could alleviate the pathological progress of DN by activating Nrf2/ARE signaling and diminishing the excessive oxidative stress and fibronectin (FN) accumulation in glomerular mesangial cells (GMCs) challenged with high glucose (HG). In the current study, we found that AST treatment alleviated the metabolic parameters, renal morphology and extracellular matrix (ECM) accumulation in streptozotocin-induced diabetic rats. Additionally, HG induced the adaptively activated Nrf2/ARE signaling and increased the expression of FN, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1), as well as the intracellular reactive oxygen species (ROS) generation in GMCs. However, AST treatment strongly promoted the nuclear translocation and transcriptional activity of Nrf2 as well as upregulated the expression of superoxide dismutase (SOD1), NAD(P)H: quinone oxidoreductase (NQO1) and heme oxygenase-1 (HO-1), ultimately quenching the higher level of ROS and inhibiting the FN, ICAM-1 and TGF-β1 expression induced by HG. Collectively, our data suggest that the renoprotective effect of AST on DN depends on Nrf2/ARE signaling activation, which could be a potentially therapeutic strategy in the treatment of DN. https://greenmedinfo.com/article/astaxanthin-promotes-nrf2are-signalling-inhibit-high-glucose-induced-renal-fib#comments Astaxanthin Diabetic Nephropathy Kidney Fibrosis Antioxidants Nrf2 activation Renoprotective Antioxidants Astaxanthin Diabetic Nephropathy Kidney Fibrosis Nrf2 activation Renoprotective Animal Study Tue, 10 Apr 2018 22:13:04 +0000 greenmedinfo 162422 at https://greenmedinfo.com Carnosic acid prevents dextran sulfate sodium-induced acute colitis. https://greenmedinfo.com/article/carnosic-acid-prevents-dextran-sulfate-sodium-induced-acute-colitis n/a PMID:  Sci Rep. 2017 Sep 8 ;7(1):11036. Epub 2017 Sep 8. PMID: 28887507 Abstract Title:  Carnosic acid prevents dextran sulfate sodium-induced acute colitis associated with the regulation of the Keap1/Nrf2 pathway. Abstract:  Crohn&#039;s disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with high prevalence in humans. Carnosic acid (CA) has been reported to possess antioxidative properties; however, its role in IBDs has not been determined. In the present study, we found that CA significantly prevented the loss of body weight and shortening of colon length in acute colitis induced by dextran sodium sulfate (DSS). Pronounced infiltration of immune cells and a loss of crypt architecture and goblet cells were ameliorated by CA. CA significantly decreased the activity of MPO and infiltration of F4/80macrophages in the colon. DSS-induced pro-inflammatory cytokine mRNA and protein levels in the colon were also attenuated by CA. CA decreased the activation of p65 and c-Jun signalling. CA inhibited DSS-induced NLRP3 inflammasome activation by reducing caspase 1 activity. In addition, CA increased the level of Nrf2 and prevented the degradation of Nrf2 via ubiquitination by blocking the interaction between Cullin3 and Keap1, which resulted in the decrease of Nrf2 target genes. Finally, GSH levels and SOD activity were increased after CA treatment, while MDA and iNOS levels were significantly reduced. Taken together, our data showed that CA may be useful as a potential therapeutic candidate for IBDs. https://greenmedinfo.com/article/carnosic-acid-prevents-dextran-sulfate-sodium-induced-acute-colitis#comments Carnosic Acid Colitis Antioxidants Nrf2 activation Antioxidants Carnosic Acid Colitis Nrf2 activation In Vitro Study Fri, 25 May 2018 01:13:29 +0000 greenmedinfo 164768 at https://greenmedinfo.com Fucoxanthin provides neuroprotection in models of traumatic brain injury. https://greenmedinfo.com/article/fucoxanthin-provides-neuroprotection-models-traumatic-brain-injury n/a PMID:  Sci Rep. 2017 Apr 21 ;7:46763. Epub 2017 Apr 21. PMID: 28429775 Abstract Title:  Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways. Abstract:  Fucoxanthin is abundant in seaweed and is considered as a powerful antioxidant. It has been proposed to possess anti-cancer, anti-obesity and anti-diabetes effects. However, its roles in brain injury models have not been fully understood. The objective of this study was to investigate the neuroprotection of fucoxanthin in models of traumatic brain injury (TBI) and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-response element (ARE) and Nrf2-autophagy pathways in the putative neuroprotection. We found that fucoxanthin alleviated TBI-induced secondary brain injury, including neurological deficits, cerebral edema, brain lesion and neuronal apoptosis. Moreover, the up-regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were reversed by fucoxanthin treatment. Furthermore, our in vitro studies demonstrated that fucoxanthin increased the neuron survival and reduced the reactive oxygen species (ROS) level. In addition, fucoxanthin activated the Nrf2-ARE pathway and autophagy both in vivo and in vitro, which was proven by the results of immunohistochemistry, western blot and electrophoretic mobility shift assay (EMSA). However, fucoxanthin failed to provide neuroprotection and activated autophagy following TBI in Nrf2(-/-) mice. In conclusion, our studies indicated that fucoxanthin provided neuroprotective effects in models of TBI, potentially via regulation of the Nrf2-ARE and Nrf2-autophagy pathways. https://greenmedinfo.com/article/fucoxanthin-provides-neuroprotection-models-traumatic-brain-injury#comments Brain Injury: Traumatic Fucoxanthin Antioxidants Neuroprotective Agents Nrf2 activation Antioxidants Brain Injury: Traumatic Fucoxanthin Neuroprotective Agents Nrf2 activation Animal Study In Vitro Study Tue, 30 May 2017 22:40:56 +0000 greenmedinfo 148430 at https://greenmedinfo.com Phloretin has a strong chemopreventive effect against aflatoxin B1. https://greenmedinfo.com/article/phloretin-has-strong-chemopreventive-effect-against-aflatoxin-b1 n/a PMID:  Biofactors. 2012 Jan-Feb;38(1):34-43. Epub 2012 Jan 18. PMID: 22253071 Abstract Title:  Dual effects of phloretin on aflatoxin B1 metabolism: activation and detoxification of aflatoxin B1. Abstract:  Typically, chemopreventive agents involve either induction of phase II detoxifying enzymes and/or inhibition of cytochrome P450 enzymes (CYPs) that are required for the activation of procarcinogens. In this study, we investigated the protective effects of phloretin against aflatoxin B1 (AFB1) activation to the ultimate carcinogenic intermediate, AFB(1)-8, 9-epoxide (AFBO), and its subsequent detoxification. Phloretin markedly inhibited formation of the epoxide with human liver microsomes in a dose-dependent manner. Phloretin also inhibited the activities of nifedipine oxidation and ethoxyresorufin O-deethylase (EROD) in human liver microsomes. These data show that phloretin strongly inhibits CYP1A2 and CYP3A4 activities, which are involved in the activation of AFB1. Phloretin increased glutathione S-transferase (GST) activity of alpha mouse liver 12 (AML 12) cells in a dose-dependent manner. GST activity toward AFBO in cell lysates treated with 20μM phloretin was 23-fold that of untreated control cell lysates. The expression of GSTA3, GSTA4, GSTM1, GSTP1 and GSTT1 was induced by phloretin in a dose-dependent manner in AML 12 cells. GSTP1, GSTM1, and GSTT1 were able to significantly increase the conjugation of AFBO with glutathione. Concurrently, induction of the GST isozyme genes was partially associated with the Nrf2/ARE pathway. Taken together, the results demonstrate that phloretin has a strong chemopreventive effect against AFB1 through its inhibitory effect on CYP1A2, CYP3A4, and its inductive effect on GST activity. https://greenmedinfo.com/article/phloretin-has-strong-chemopreventive-effect-against-aflatoxin-b1#comments Liver Damage: Aflatoxin-Induced Phloretin Aflatoxin Chemopreventive Nrf2 activation Chemopreventive Dose Response Liver Damage: Aflatoxin-Induced Nrf2 activation Phloretin In Vitro Study Fri, 03 Mar 2017 22:05:48 +0000 greenmedinfo 144368 at https://greenmedinfo.com Piper nigrum might be a promising candidate for the treatment of inflammatory diseases. https://greenmedinfo.com/article/piper-nigrum-might-be-promising-candidate-treatment-inflammatory-diseases n/a PMID:  Phytother Res. 2017 Feb 10. Epub 2017 Feb 10. PMID: 28185326 Abstract Title:  Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway. Abstract:  In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7-dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7-dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 6.8, 14.5, 30.2, 23.7, and 38.5 μM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50 value of 9.5 μM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) suppressedexpression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley&amp;Sons, Ltd. https://greenmedinfo.com/article/piper-nigrum-might-be-promising-candidate-treatment-inflammatory-diseases#comments Black Pepper Inflammation Heme oxygenase-1 inducer Nrf2 activation Black Pepper Heme oxygenase-1 inducer Inflammation Nrf2 activation In Vitro Study Sat, 04 Mar 2017 00:28:48 +0000 greenmedinfo 144392 at https://greenmedinfo.com Sulforphane's antioxidant properties make it an effective neuroprotective agent. More studies are needed to determine the exact implications in neurological disease. https://greenmedinfo.com/article/sulforphanes-antioxidant-properties-make-it-effective-neuroprotective-agent-mo PMID:  Brain Circ. 2019 Apr-Jun;5(2):74-83. Epub 2019 Jun 27. PMID: 31334360 Abstract Title:  The neuroprotective mechanisms and effects of sulforaphane. Abstract:  Sulforaphane (SFN) is a phytochemical found in cruciferous vegetables. It has been shown to have many protective effects against many diseases, including multiple types of cancer. SFN is a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (ARE) genetic pathway. Upregulation of Nrf2-ARE increases the availability of multiple antioxidants. A substantial amount of preclinical research regarding the ability of SFN to protect the nervous system from many diseases and toxins has been done, but only a few small human trials have been completed. Preclinical data suggest that SFN protects the nervous system through multiple mechanisms and may help reduce the risk of many diseases and reduce the burden of symptoms in existing conditions. This review focuses on the literature regarding the protective effects of SFN on the nervous system. A discussion of neuroprotective mechanisms is followed by a discussion of the protective effects elicited by SFN administration in a multitude of neurological diseases and toxin exposures. SFN is a promising neuroprotective phytochemical which needs further human trials to evaluate its efficacy in preventing and decreasing the burden of many neurological diseases. <p><a href="https://greenmedinfo.com/article/sulforphanes-antioxidant-properties-make-it-effective-neuroprotective-agent-mo" target="_blank">read more</a></p> https://greenmedinfo.com/article/sulforphanes-antioxidant-properties-make-it-effective-neuroprotective-agent-mo#comments Sulforaphane Antioxidant antioxidant Antioxidant Effects Antioxidants antioxidants neuro-protective Neuroprotective Agents NF-E2-Related Factor-2 (Nrf2) Modulator Nrf2 activation Antioxidant effects Antioxidant Systems Cruciferous Vegetables Neurodegenerative diseases Neuroprotective Agents Nrf2 activation Phytotherapy Sulforaphane Review Wed, 24 Jul 2019 18:33:49 +0000 greenmedinfo 191800 at https://greenmedinfo.com The effect of rutin and hesperidin on the expression of Nrf2- and AhR-regulated genes and CYP3A1 gene in rats intoxicated with carbon tetrachloride https://greenmedinfo.com/article/effect-rutin-and-hesperidin-expression-nrf2-and-ahr-regulated-genes-and-cyp3a1 n/a PMID:  Vopr Pitan. 2016 ;85(5):28-35. PMID: 29381299 Abstract Title:  [The effect of rutin and hesperidin on the expression of Nrf2- and AhR-regulated genes and CYP3A1 gene in rats intoxicated with carbon tetrachloride]. Abstract:  The purpose of the study was to determine the effects of rutin (R) and hesperidin (Hes), the main representatives of two most studied subclasses of flavonoids - flavonols and flavanones, on the expression of prototypical Nrf2 and AhR-regulated genes and CYP3A1 gene in rats intoxicated with carbon tetrachloride (CCl4). Investigations were carried out on 5 groups of male Wistar rats with the initial body weight (b.w.) 180-200 g (n=40). Rats of the control group and the 1st experimental group received for 14 days the semisynthetic diet, rats of the 2nd experimental group - the same diet plus R (400 mg/kg b.w.), the animals of the 3rd experimental group received the diet with Hes in the same amount, of the 4th experimental group - diet with R (400 mg/kg b.w.) and Hes (400 mg/kg b.w.). Animals of the experimental groups 24 hours before the end of experiment were injected intraperitoneally CCl4 at a dose of 0.5 ml/kg b.w. in olive oil; rats of the control group were injected equal amount of olive oil. For gene expression assessment the mRNA content of NAD(P)H-quinone oxidoreductase (NQO1), heme oxygenase-1 (Hmox1), Nrf2 (Nrf2), AhR (AhR), CYP1A1, CYP1A2, CYP3A1 andβ-actin (Actb) in rat liver was determined by real-time RT-PCR. The results showed that in rats intoxicated with CCl4, enrichment of the diet with R, but not with Hes, led to a significant increase in the expression of genes Hmox1, NQO1 and CYP3A1. Combined intake of R and Hes with the diet led toadditivity of their action on the expression of Hmox1 gene and to synergism in the effect on the expression of genes NQO1 and CYP3A1. A moderate increase in the levels of expression of AhR and CYP1A2 genes as compared to their expression in rats treated with CCl4 only, CCl4 and R or CCl4 and Hes hasbeen noted. Thus, for the first time on the model of oxidative stress in rats the data have been obtained showing at the gene expression level a synergism of action of two flavonoids - R and Hes, widely present in the daily human diet. https://greenmedinfo.com/article/effect-rutin-and-hesperidin-expression-nrf2-and-ahr-regulated-genes-and-cyp3a1#comments Hesperidin Rutin Antioxidants Calcium Carbonate Heme oxygenase-1 up-regulation Nrf2 activation Antioxidants Calcium Carbonate Gene Expression Regulation Heme oxygenase-1 up-regulation Hesperidin Nrf2 activation Rutin Animal Study Thu, 08 Feb 2018 04:34:27 +0000 greenmedinfo 159500 at https://greenmedinfo.com Thymoquinone protects against cobalt chloride-induced neurotoxicity. https://greenmedinfo.com/article/thymoquinone-protects-against-cobalt-chloride-induced-neurotoxicity n/a PMID:  J Biol Regul Homeost Agents. 2017 Oct-Dec;31(4):843-853. PMID: 29254287 Abstract Title:  Thymoquinone protects against cobalt chloride-induced neurotoxicity via Nrf2/GCL-regulated glutathione homeostasis. Abstract:  The prevalence of neurodegenerative diseases worldwide has increased dramatically in the last decades. Hypoxia and oxidative stress play a central role in the pathogenesis of neurodegenerative diseases. Thymoquinone (TQ) is a monoterpenoid hydrocarbon compound that possesses potent antioxidant activity. In the current study, we investigated the neuroprotective effects of TQ against CoCl2, a widely used hypoxia-inducing agent. We found that TQ inhibited CoCl2-indcued cytotoxicity in vitro, as reflected by an increase of cell viability and decrease of apoptosis in CoCl2-treated PC12 cells. TQ exhibited a potent protective effect against CoCl2-induced neurotoxicity in vivo, as evidenced by decreased time spent to find the platform site in the Probe trials, reduced escape latencies, decreased traveling distance and reduction of apoptotic cell death in brains in CoCl2-treated rats. CoCl2-resulted decrease of glutathione (GSH) and increase of malondialdehyde (MDA) levels were significantly inhibited by TQ. Inhibition of GSH synthesis by buthionine sulphoximine (BSO) significantly attenuated TQ-induced neuroprotective effects against CoCl2 in rats and in PC12 cells. TQ could upregulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLc) and Nrf2/glutamate-cysteine ligase modifier subunit (GCLm) pathway which contributed to antioxidant and neuroprotective effects of TQ. In summary, we found that TQ exhibited protective effects against neurotoxicity via upregulation of Nrf2/GCL signaling. Upregulation of Nrf2/GCL signaling promoted the synthesis of GSH and contributed to attenuation of oxidative stress, neuronal cell apoptosis and neurotoxicity. These data have appointed a new path toward the understanding of the neuroprotective activities of TQ. https://greenmedinfo.com/article/thymoquinone-protects-against-cobalt-chloride-induced-neurotoxicity#comments Neurodegenerative Diseases Thymoquinone Antioxidants Cobalt Neuroprotective Agents Nrf2 activation Antioxidants Cobalt Neurodegenerative diseases Neuroprotective Agents Nrf2 activation thymoquinone In Vitro Study Tue, 09 Jan 2018 19:25:04 +0000 greenmedinfo 158249 at https://greenmedinfo.com