Thymoquinone Improved Nonylphenol-Induced Memory Deficit and Neurotoxicity Through its Antioxidant and Neuroprotective Effects

Abstract Nonylphenol (NP), a well-known endocrine-disrupter chemical, has several harmful effects on the central nervous system including neuroendocrine disruption, cognitive impairment, and neurotoxicity. Thymoquinone (TQ) is a main bioactive compound in the black seeds of Nigella sativa that has antioxidant, anti-inflammatory, and neuroprotective properties. Here, we investigated the neuroprotective effect of TQ against NP-induced memory deficit and neurotoxicity in rats. To induce memory impairment, NP (25 mg/kg) was used as gavage in male Wistar rats for 21 days. TQ (2.5, 5 and 10mg/kg) was intraperitoneally administered in NP-treated animals. The morris water maze test was performed to assess spatial learning and memory. The hippocampal tissues were isolated from the brain for histopathological evaluation. Biochemical, molecular and cellular tests were performed to quantify oxidant (malondialdehyde; MDA)/antioxidant (superoxide dismutase (SOD), total antioxidant capacity (TAC) and reduced glutathione (GSH) parameters as well as markers for astrocytic activation (glial fibrillary acidic protein; GFAP) and neuronal death (alpha-synuclein; α-syn). Results showed TQ (5 mg/kg) significantly improved NP-induced memory impairment. Histological data revealed a significant increase in the number of necrotic cells in hippocampus, and TQ treatment markedly decreased this effect. The GSH and TAC levels were significantly increased in TQ-treated groups compared to NP group. The molecular analysis indicated that NP increased GFAP and decreased α-syn expression and TQ treatment did the reverse. In vitro study in astrocytes isolated from mice brain showed that TQ significantly increased cell viability in NP-induced cytotoxicity. This study strongly indicates that TQ has neuroprotective effects on NP-induced neurotoxicity through reducing oxidative damages and neuroinflammation.

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Thymoquinone Improved Nonylphenol-Induced Memory Deficit and Neurotoxicity Trough its Antioxidant and Neuroprotective Effects

10.21203/rs.3.rs-920975/v1 ◽

2021 ◽

Author(s):

Mandana Lotfi ◽

Sohrab Kazemi ◽

Anahita Ebrahimpour ◽

Fereshteh Pourabdolhossein ◽

Seyed Leila Satarian ◽

...

Keyword(s):

Memory Impairment ◽

Nigella Sativa ◽

Neuroprotective Effect ◽

In Vitro Study ◽

Bioactive Compound ◽

Memory Deficit ◽

Neuroprotective Effects ◽

Oxidative Damages ◽

Male Wistar Rats

Abstract Nonylphenol (NP) as a well-known endocrine-disrupter chemical (EDCs), has several harmful effects on the CNS such as neuroendocrine disruption, cognitive impairment, and neurotoxicity. Thymoquinone (TQ) is a main bioactive compound in the black seeds of nigella sativa (NS) possesses antioxidant, anti-inflammatory, and neuroprotective properties. This study was designed to assess the neuroprotective effect of TQ against NP-induced memory deficit and neurotoxicity in rats. To induce memory impairment, NP (25mg/kg) was used as gavage in male Wistar rats for 21 days. TQ i.p. injection at doses 2.5, 5, and 10mg/kg was done in NP-treated animals at the same time. Morris Water Maze (MWM) test was performed to assess spatial memory. The rats` hippocampus tissues were isolated for histopathological testes. Biochemical, molecular and cellular tests were done for proving more details. The results showed TQ at dose 5 mg/kg significantly improved NP-induced memory impairment. Histological data proved that TQ decreased the number of necrotic cells in the hippocampus which was increased in NP-treated animals. Biochemical analysis showed that the levels of glutathione (GSH) and total antioxidant capacity (TAC) were significantly increased in TQ treated groups compared to the NP group. The molecular analysis has shown that NP increased GFAP and decreased α-Syn expression level and TQ treatment did the reverse. In vitro study in astrocytes isolated from mice brain proved that TQ significantly increased cell viability in cytotoxicity induced by NP. This study strongly indicates that TQ has therapeutic and neuroprotective effects on NP-induced neurotoxicity through reduction of oxidative damages and neuroinflammation.

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NEUROPROTECTIVE EFFECTS OF GUARANA (PAULLINIA CUPANA MART.) AGAINST VINCRISTINE IN VITRO EXPOSURE

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2017.45 ◽

2017 ◽

pp. 1-6

Author(s):

C.F. Veloso ◽

A.K. Machado ◽

F.C. Cadoná ◽

V.F. Azzolin ◽

I.B.M. Cruz ◽

...

Keyword(s):

Cell Viability ◽

Monolayer Culture ◽

Cell Damage ◽

Neuroprotective Effect ◽

In Vitro Study ◽

Oxygen Species ◽

Neuroprotective Effects ◽

Hydroalcoholic Extract ◽

Mice Brain

Background: Vincristine (VCR) is not a specific chemotherapeutic drug, responsible for cause several side effects. In this sense, many natural products have been studied to reduce this problem. Objetives: To examine the guarana neuroprotective effect in mice brain and cerebellum cells against vincristine (VCR) exposition. Design: An in vitro study was performed using mice brain and cerebellum mice in monolayer culture. First, cells were exposed to VCR (0.009 µM for 24 hours and 0.0007 µM for 72 hours) to measure the cytotoxicity effect. Also, the cellular effect of hydroalcoholic extract of guarana (10; 30; 100 and 300 μg/mL) was evaluated in the same cells in 24 and 72 hours. After that, cells were exposed to VCR and guarana extract to evaluate the neuroprotective effect of guarana. Measurements: Cell viability was analyzed by MTT, Free dsDNA and LHD Assays. Moreover, metabolism oxidative profile was evaluated by reactive oxygen species (ROS), lipoperoxidation (LPO) and catalase (CAT) levels through DCFH-DA, TBARS and Catalase Activity Assays, respectively. Results: Our findings revealed that VCR caused neuronal cytotoxicity by reducing cell viability and increasing ROS and LPO levels. On the other hand, guarana did not cause cell damage in none of tested concentrations. In addition, guarana exhibited a notable protective effect on brain and cerebellum cells exposed to VCR by increasing cell viability, stimulating CAT activity, reducing levels of ROS and LPO. Conclusions: In this sense, guaraná is a remarkable antioxidant fruit that could be a target in new therapies development to reduce VCR neurotoxicity.

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Neuroprotective effect of Danshensu derivatives as anti-ischaemia agents on SH-SY5Y cells and rat brain

Bioscience Reports ◽

10.1042/bsr20130032 ◽

2013 ◽

Vol 33 (4) ◽

Cited By ~ 14

Author(s):

Sunisa Seetapun ◽

Jia Yaoling ◽

Yang Wang ◽

Yi Zhun Zhu

Keyword(s):

Rat Brain ◽

Infarct Volume ◽

Neuroprotective Effect ◽

In Vitro Study ◽

Artery Occlusion ◽

Neuroprotective Effects ◽

Inhibit Lipid Peroxidation ◽

Cysteine Derivative

Novel Danshensu derivatives (3–8) were designed and synthesized to improve bioactivity based on the strategy of ‘medicinal chemical hybridization’. Our previous studies indicated that these compounds exhibited noticeable cardioprotective activities. Here, we investigate whether these novel Danshensu derivatives exert neuroprotective activities. An in vitro study revealed that these compounds could increase cell viability and reduce LDH (lactate dehydrogenase) leakage. Moreover, Danshensu-cysteine derivative compounds 6 and 8 could significantly inhibit lipid peroxidation of cell membrane and regulate the expression of apoptosis-related protein (Bcl-2, Bax and caspase 3). An in vivo study demonstrated that treatment with compound 6 at 30 mg/kg markedly decreased the infarct volume of MCAO (middle cerebral artery occlusion) insulted rat brain. Furthermore, treatment with compound 6 showed the antioxidant capacity by increasing the activity of SOD (superoxide dismutase) and GPx (glutathione peroxidase) and decreasing the level of MDA (malondialdehyde) and the ROS (reactive oxygen species) production significantly. These results suggested that these novel conjugates exert significant neuroprotective effects as anti-ischaemia agents and those with high potential merit further investigation.

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Pinocembrin ameliorates intermittent hypoxia-induced neuroinflammation through BNIP3-dependent mitophagy in a murine model of sleep apnea

Journal of Neuroinflammation ◽

10.1186/s12974-020-02014-w ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Lin-Jing Gong ◽

Xin-Yuan Wang ◽

Wen-Yu Gu ◽

Xu Wu

Keyword(s):

Sleep Apnea ◽

Nlrp3 Inflammasome ◽

Intermittent Hypoxia ◽

Morris Water Maze Test ◽

Spatial Learning And Memory ◽

Mitochondrial Morphology ◽

Neuroprotective Effects ◽

Obstructive Sleep ◽

Custom Made

Abstract Background Intermittent hypoxia (IH) caused by obstructive sleep apnea (OSA) leads to neuroinflammation. Pinocembrin has been shown to have neuroprotective effects, while the therapeutic functions under IH condition are still unknown. Methods An OSA model was established by CIH exposure inside custom-made chambers. C57BL/6 mice were intraperitoneally injected with pinocembrin (40 mg/kg, i.p.) or vehicle (PBS containing 5% povidone; i.p.), and the changes of behavior on mice were detected by the Morris water maze test. Immunohistochemical staining, western blotting, immunofluorescence assays, and immunoprecipitation were used to investigate the association between NLRP3 inflammasome and BNIP3-dependent mitophagy. The mitochondrial morphology and mitophagosomes were detected under a transmission electron microscope. The detrimental effects of IH were tested by annexin V-FITC/PI staining, Mito SOX Red staining, and JC-1 mitochondrial membrane potential assay. Results In this study, our observations in vivo indicated that the administration of pinocembrin can restore spatial learning and memory ability and reduce neuronal apoptosis and hippocampal inflammation. Pinocembrin treatment significantly inhibited the formation of NLRP3 inflammasome and infiltration of microglia and enhanced BNIP3-mediated mitophagy in the hippocampus of IH mice. Additionally, our in vitro results show that pinocembrin protects microglial cells against IH-induced cytotoxicity by activating BNIP3-dependent mitophagy through the JNK-ERK signaling pathway. Conclusions In summary, our findings demonstrated that pinocembrin can act as a potential therapeutic strategy for IH-induced neuroinflammation.

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Cognitive Enhancing and Neuroprotective Effect of the Embryo of theNelumbo nuciferaSeed

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/869831 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Eun Sil Kim ◽

Jin Bae Weon ◽

Bo-Ra Yun ◽

Jiwoo Lee ◽

Min Rye Eom ◽

...

Keyword(s):

Memory Impairment ◽

Neuroprotective Effect ◽

Acetylcholinesterase Inhibition ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

Treatment And Prevention ◽

Maze Test ◽

Ht22 Cell ◽

Underlying Mechanisms

The aim of the present study was to evaluate the effect of ENS on cognitive impairment induced by scopolamine and its potential neuroprotective effect against glutamate-induced cytotoxicity in HT22 cell and to investigate the underlying mechanisms. ENS (3, 10, 30, and 100 mg/kg), scopolamine (1 mg/kg), and donepezil (1 mg/kg) were administered to mice during a test period. Scopolamine impaired memory and learning in a water maze test and a passive avoidance test. The neuroprotective effect of ENS (10 and 100 μg/mL) was investigated on glutamate-induced cell death in HT22 cells by MTT assay. We investigated acetylcholinesterase inhibition in hippocampus and antioxidant activity, ROS levels, and Ca2+influx in HT22 cells to elucidate the potential mechanisms of ENS. We found that ENS significantly ameliorated scopolamine-induced memory impairment and inhibited AChE activity in hippocampus.In vitro, ENS showed potent neuroprotective effects against glutamate-induced neurotoxicity in the HT22 cell. In addition, ENS induced a decrease in ROS production and intercellular Ca2+accumulation and showed DPPH radical and H2O2scavenging activity. In conclusion, ENS showed both a memory improving effect and a neuroprotective effect. Our results indicate that ENS may be of use in the treatment and prevention of neurodegenerative disorders.

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Lactobacilli-fermented cow's milk attenuated lipopolysaccharide-induced neuroinflammation and memory impairment in vitro and in vivo

Journal of Dairy Research ◽

10.1017/s0022029917000620 ◽

2017 ◽

Vol 84 (4) ◽

pp. 488-495 ◽

Cited By ~ 28

Author(s):

Nurul Huda Musa ◽

Vasudevan Mani ◽

Siong Meng Lim ◽

Sharmili Vidyadaran ◽

Abu Bakar Abdul Majeed ◽

...

Keyword(s):

Nitrosative Stress ◽

Neuroprotective Effect ◽

Memory Deficit ◽

Morris Water Maze Test ◽

Cow’S Milk ◽

Cow's Milk ◽

Cytokine Analysis ◽

Bv2 Cells ◽

Anti Inflammation

Nutritional interventions are now recommended as strategies to delay Alzheimer's disease (AD) progression. The present study evaluated the neuroprotective effect (anti-inflammation) of lactic acid bacteria (either Lactobacillus fermentum LAB9 or L. casei LABPC) fermented cow's milk (CM) against lipopolysaccharide (LPS)-activated microglial BV2 cells in vitro. The ability of CM-LAB in attenuating memory deficit in LPS-induced mice was also investigated. ICR mice were orally administered with CM-LAB for 28 d before induction of neuroinflammation by LPS. Learning and memory behaviour were assessed using the Morris Water Maze Test. Brain tissues were homogenised for measurement of acetylcholinesterase (AChE), antioxidative, lipid peroxidation (malondialdehyde (MDA)) and nitrosative stress (NO) parameters. Serum was collected for cytokine analysis. CM-LAB9 and CM-LABPC significantly (P < 0·05) decreased NO level but did not affect CD40 expression in vitro. CM-LAB attenuated LPS-induced memory deficit in mice. This was accompanied by significant (P < 0·05) increment of antioxidants (SOD, GSH, GPx) and reduction of MDA, AChE and also pro-inflammatory cytokines. Unfermented cow's milk (UCM) yielded greater cytokine lowering effect than CM-LAB. The present findings suggest that attenuation of LPS-induced neuroinflamation and memory deficit by CM-LAB could be mediated via anti-inflammation through inhibition of AChE and antioxidative activities.

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Neuroprotective and anti-amnestic effects of a combination therapy in a model of photochemical ischemic damage in the prefrontal cortex

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2018.02.39-45 ◽

2018 ◽

pp. 39-45

Author(s):

Ф.М. Шакова ◽

Т.И. Калинина ◽

М.В. Гуляев ◽

Г.А. Романова

Keyword(s):

Prefrontal Cortex ◽

Nerve Growth Factor ◽

Growth Factor ◽

Combination Therapy ◽

Neuroprotective Effect ◽

Regulatory Protein ◽

Human Growth ◽

Neuroprotective Effects ◽

Nerve Growth

Цель исследования - изучение влияния комбинированной терапии (мутантные молекулы эритропоэтина (EPO) и дипептидный миметик фактора роста нервов ГК-2H) на воспроизведение условного рефлекса пассивного избегания (УРПИ) и объем поражения коры мозга у крыс с двусторонним ишемическим повреждением префронтальной коры. Методика. Мутантные молекулы EPO (MЕРО-TR и MЕPО-Fc) с значительно редуцированной эритропоэтической и выраженной цитопротекторной активностью созданы методом генной инженерии. Используемый миметик фактора роста нервов человека, эндогенного регуляторного белка, в экспериментах in vitro проявлял отчетливые нейропротективные свойства. Двустороннюю фокальную ишемию префронтальной коры головного мозга крыс создавали методом фотохимического тромбоза. Выработку и оценку УРПИ проводили по стандартной методике. Объем повреждения мозга оценивался при помощи МРТ. MEPO-TR и MEPO-Fc (50 мкг/кг) вводили интраназально однократно через 1 ч после фототромбоза, ГК-2Н (1 мг/кг) - внутрибрюшинно через 4 ч после фототромбоза и далее в течение 4 послеоперационных суток. Результаты. Выявлено статистически значимое сохранение выработанного до ишемии УРПИ, а также значимое снижение объема повреждения коры при комплексной терапии. Полученные данные свидетельствуют об антиамнестическом и нейропротекторном эффектах примененной комбинированной терапии, которые наиболее отчетливо выражены в дозах: МEPO-Fc (50 мкг/кг) и ГК-2Н (1 мг/кг). Заключение. Подтвержден нейропротекторный эффект и усиление антиамнестического эффекта при сочетанном применении мутантных производных эритропоэтина - MEPO-TR и MEPO-Fc и дипептидного миметика фактора роста нервов человека ГК-2H. The aim of this study was to investigate the effect of combination therapy, including mutant erythropoietin molecules (EPO) and a dipeptide mimetic of the nerve growth factor, GK-2H, on the conditioned passive avoidance (PA) reflex and the volume of injury induced by bilateral ischemia of the prefrontal cortex in rats. Using the method of genetic engineering the mutant molecules of EPO, MERO-TR and MEPO-Fc, with strongly reduced erythropoietic and pronounced cytoprotective activity were created. The used human nerve growth factor mimetic, an endogenous regulatory protein based on the b-bend of loop 4, which is a dimeric substituted dipeptide of bis- (N-monosuccinyl-glycyl-lysine) hexamethylenediamine, GK-2 human (GK-2H), has proven neuroprotective in in vitro experiments. Methods. Bilateral focal ischemic infarction was modeled in the rat prefrontal cortex by photochemically induced thrombosis. The PA test was performed according to a standard method. Volume of brain injury was estimated using MRI. MEPO-TR, and MEPO-Fc (50 mg/kg, intranasally) were administered once, one hour after the injury. GK-2Н (1 mg/kg, i.p.) was injected four hours after the injury and then for next four days. Results. The study showed that the complex therapy provided statistically significant retention of the PA reflex developed prior to ischemia and a significant decrease in the volume of injury. The anti-amnestic and neuroprotective effects of combination therapy were most pronounced at doses of MEPO-Fc 50 mg/kg and GK-2H 1 mg/kg. Conclusion. This study has confirmed the neuroprotective effect and enhancement of the anti-amnestic effect exerted by the combination of mutant erythropoietin derivatives, MEPO-TR and MEPO-Fc, and the dipeptide mimetic of human growth factor GK-2H.

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