Oxidative Stress In Mouse Brain Research Articles

Apigenin Alleviates Autistic-like Stereotyped Repetitive Behaviors and Mitigates Brain Oxidative Stress in Mice.

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10-30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 mg/kg, i.p.). BTBR mice pretreated with APG (20 mg/kg) or ARP (1 mg/g, i.p.) displayed significant improvements in the marble-burying test (MBT), cotton-shredding test (CST), and self-grooming test (SGT) (all p < 0.05). However, a lower dose of APG (10 mg/kg, i.p.) failed to modulate behaviors in the MBT or SGT, but significantly attenuated the increased shredding behaviors in the CST of tested mice. Moreover, APG (10-30 mg/kg, i.p.) and ARP (1 mg/kg) moderated the disturbed levels of oxidative stress by mitigating the levels of catalase (CAT) and superoxide dismutase (SOD) in the hippocampus and cerebellum of treated BTBR mice. In patch clamp studies in hippocampal slices, the potency of choline (a selective agonist of α7-nAChRs) in activating fast inward currents was significantly potentiated following incubation with APG. Moreover, APG markedly potentiated the choline-induced enhancement of spontaneous inhibitory postsynaptic currents. The observed results propose the potential therapeutic use of APG in the management of ASD. However, further preclinical investigations in additional models and different rodent species are still needed to confirm the potential relevance of the therapeutic use of APG in ASD.

Protective Effects of N-Acetylcysteine on Dipentyl Phthalate Induced Cognitive Dysfunction and Brain Oxidative Stress in Mice

Background: Dipentyl phthalate (DPeP) is a plasticizer compound commonly used in polyvinylchloride plastic to enhance softness and flexibility. They are not bound covalently to plastic polymers; therefore, they can dissolve into the environment and adversely affect the health of humans and animals.&#x0D; Objectives: The aim of this study was to investigate the effect of DPeP on cognition and protective effects of N-acetylcysteine (NAC) on DPeP induced alteration in cognitive behaviour and oxidative stress markers in mice.&#x0D; Methods: Mice were orally treated with 2 doses (33 mg/kg and 100 mg/kg) of DPeP for 28 days. Cognitive functions were assessed using spatial navigation tasks on the Morris water maze and the step-down latency in the passive avoidance apparatus. Oxidative stress was assessed by examining the levels of malondialdehyde, glutathione, ferric reducing antioxidant power, and 8-hydroxy-deoxyguanosine levels in the whole brain of mice.&#x0D; Results: There was a significant increase in latency in spatial navigation tasks and a significant decline in the step-down latency in passive avoidance apparatus in the DPeP-treated group compared to the control groups. There was also a significant increase in the levels of oxidative stress following DPeP administration as seen with the rise in the levels of malondialdehyde, 8-hydroxy-deoxyguanosine, and a fall in glutathione and ferric reducing antioxidant power levels.&#x0D; Conclusion: The present study demonstrated that DPeP adversely affects learning and memory functions in mice by oxidative stress-mediated neuronal damage. These effects were attenuated by pretreatment with N-acetylcysteine.

Medicinal Plants Extracts Impact on Oxidative Stress in Mice Brain Under the Physiological Conditions: the Effects of Corn Silk, Parsley, and Bearberry.

This study was performed to examine the effects of medicinal plant extracts of corn silk (Stigma maydis), parsley leaf (Petroselini folium), and bearberry leaf (Uvae ursi folium) on antioxidant status of the brain of experimental animals (mice) under the physiological conditions. Biological properties of these plants are insufficiently investigated and the aim was to explore their possible antioxidant effects that can alleviate oxidative damage of the brain tissue. Corn silk extract showed positive effect on activities of antioxidant enzymes in mice brain tissue. Parsley extract induced the increase in glutathione content and decrease of lipid peroxidation. Bearberry leaf extract induced catalase activity and decrease of hydroxyl radical content, while malonyldialdehide accumulation was maintained at the control level. Results obtained in this study support the use of corn silk, parsley and bearberry leaves as natural antioxidant sources in the prevention and treatment of brain tissue damages and different diseases caused by oxidative stress.

Swimming exercise attenuates anxiety-like behavior by reducing brain oxidative stress in type 2 diabetic mice

Anxiety-related behaviors are among the most prevalent psychiatric disorders in patients with type 2 diabetes (T2D). The protective effect of exercise on neuropsychiatric disorders has been documented. However, there are no studies that examined whether swimming exercise can decrease anxiety-like symptoms in type 2 diabetes. We investigated the effects of swimming exercise on body weight, anxiety-like behavior, glucose and insulin levels, and brain oxidative stress in male C57BL/6 mice. T2D-induced mice were subjected to swimming exercise, then anxiety-like behaviors were measured by the open field, light-dark box, and elevated plus-maze tests. Glucose and insulin levels were measure in serum, and antioxidant/oxidative markers including glutathione (GSH), malondialdehyde (MDA), and glutathione disulfide (GSSG) were measured in the brain. Our findings showed that T2D increased body weight, anxiety-like symptoms, glucose and insulin resistance, and oxidative stress by increasing MDA and GSSG levels in the brain of mice. Interestingly, swimming exercise reversed these parameters in diabetic mice. Our findings clearly indicate that there is a protective impact of swimming exercise on anxiety-like behavior by reducing insulin resistance and brain oxidative stress in mice with type 2 diabetes. Further studies are needed to validate these findings in humans.

The Multi-Targeting Ligand ST-2223 with Histamine H3 Receptor and Dopamine D2/D3 Receptor Antagonist Properties Mitigates Autism-Like Repetitive Behaviors and Brain Oxidative Stress in Mice.

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by social and communicative impairments, as well as repetitive and restricted behaviors (RRBs). With the limited effectiveness of current pharmacotherapies in treating repetitive behaviors, the present study determined the effects of acute systemic treatment of the novel multi-targeting ligand ST-2223, with incorporated histamine H3 receptor (H3R) and dopamine D2/D3 receptor affinity properties, on ASD-related RRBs in a male Black and Tan BRachyury (BTBR) mouse model of ASD. ST-2223 (2.5, 5, and 10 mg/kg, i.p.) significantly mitigated the increase in marble burying and self-grooming, and improved reduced spontaneous alternation in BTBR mice (all p < 0.05). Similarly, reference drugs memantine (MEM, 5 mg/kg, i.p.) and aripiprazole (ARP, 1 mg/kg, i.p.), reversed abnormally high levels of several RRBs in BTBR (p < 0.05). Moreover, ST-2223 palliated the disturbed anxiety levels observed in an open field test (all p < 0.05), but did not restore the hyperactivity parameters, whereas MEM failed to restore mouse anxiety and hyperactivity. In addition, ST-2223 (5 mg/kg, i.p.) mitigated oxidative stress status by decreasing the elevated levels of malondialdehyde (MDA), and increasing the levels of decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in different brain parts of treated BTBR mice (all p < 0.05). These preliminary in vivo findings demonstrate the ameliorative effects of ST-2223 on RRBs in a mouse model of ASD, suggesting its pharmacological prospective to rescue core ASD-related behaviors. Further confirmatory investigations on its effects on various brain neurotransmitters, e.g., dopamine and histamine, in different brain regions are still warranted to corroborate and expand these initial data.

Protective effect of Cyperus esculentus (tiger nut) extract against scopolamine-induced memory loss and oxidative stress in mouse brain.

Objectives The juice extract of Cyperus esculentus commonly known as tiger nuts (TINUT) is widely used for its numerous health promoting effects including alleviation of symptoms associated with neurological disorders. Herein, we investigated the influence of the aqueous extract of C.esculentus on cognitive disorder and the underlying changes in acetylcholinesterase (AChE) activity and oxidative stress biomarkers in mice exposed to scopolamine. Methods C.esculentus (50-200mg/kg) or saline (10mL/kg) was given alone or with scopolamine 30min after, to male Swiss mice (6/group) daily for seven days. We evaluated the cognitive performance using Y-maze and object recognition on day seven post-treatment. Brains of the animals were afterwards processed for spectrophotometric determination of AChE activity and contents of oxidative stress biomarkers (malondialdehyde [MDA], glutathione [GSH], catalase, superoxide dismutase and nitrite). Results The extract improves cognitive function and also upturned scopolamine amnesia in mice. The extract markedly reduced brain AChE, MDA, and nitrite contents in mice injected with scopolamine (p<0.05). It also attenuated scopolamine-induced deregulated GSH contents and antioxidant enzymes in mouse brain. Conclusions The results of this study suggest that regular consumption of TINUT might offer beneficial effects in memory-related disorders.

Effect of Spondias Mombin Fruit Extract on Scopolamine-induced Memory Impairment and Oxidative Stress in Mice Brain

ABSTRACT The effect of ethanol fruit extract of Spondias mombin (FESM) against scopolamine-induced memory impairment was evaluated in mice. Swiss mice were injected with scopolamine (3 mg kg−1, i.p) and treated with FESM (25, 100, and 400 mg kg−1) or vitamin C (100 mg kg−1) for 7 d. FESM treatment prevented scopolamine-induced memory impairment on the Y-maze and novel object recognition tests, and locomotor impairment in the open field test. Further, FESM decreased acetylcholinesterase enzyme activity in the striatum, prefrontal cortex, and hippocampus of mice brain. FESM ameliorated scopolamine-induced memory impairment via enhancement of cholinergic function and inhibition of oxidative stress in mice brains.

Bacopa monnieri Supplements Offset Paraquat-Induced Behavioral Phenotype and Brain Oxidative Pathways in Mice.

Parkinson's Disease (PD) is characterized by alterations in cerebellum and basal ganglia functioning with corresponding motor deficits and neuropsychiatric symptoms. Involvement of oxidative dysfunction has been implicated for the progression of PD, and environmental neurotoxin exposure could influence such behavior and psychiatric pathology. Assessing dietary supplementation strategies with naturally occurring phytochemicals to reduce behavioral anomalies associated with neurotoxin exposure would have major clinical importance. The present investigation assessed the influence of Bacopa monneri (BM) on behaviors considered to reflect anxiety-like state and motor function as well as selected biochemical changes in brain regions of mice chronically exposed to ecologically relevant herbicide, paraquat (PQ). Male mice (4-week old, Swiss) were daily provided with oral supplements of standardized BM extract (200 mg/kg body weight/day; 3 weeks) and PQ (10 mg/kg, i.p. three times a week; 3 weeks). We found that BM supplementation significantly reversed the PQ-induced reduction of exploratory behavior, gait abnormalities (stride length and mismatch of paw placement) and motor impairment (rotarod performance). In a separate study, BM administration prevented the reduction in dopamine levels and reversed cholinergic activity in brain regions important for motor (striatum) pathology. Further, in mitochondria, PQ-induced decrease in succinate dehydrogenase (SDH) activity and energy charge (MTT reduction), was restored with BM supplementation. These findings suggest that BM supplementation mitigates paraquat-induced behavioral deficits and brain oxidative stress in mice. However, further investigations would enable us to identify specific molecular mechanism by which BM influences behavioural pathology.

Lavandula stoechas (L) a Very Potent Antioxidant Attenuates Dementia in Scopolamine Induced Memory Deficit Mice.

The objective of the current project was to explore the pharmacotherapeutic role of Lavandula stoechas (L) for the management of dementia. Dementia is considered a global challenge of current century seeking special attention of pharmacologists to explore its best remedies. Methanolic extract of aerial parts of L. stoechas was tested for phytochemical analysis along with free radical scavenging activity. Behavioral studies were performed on scopolamine induced amnesic mice by using elevated plus maze (EPM), light and dark test and hole board paradigms. Biochemical investigations were made after decapitating the mice. Their brains were isolated for biochemical estimation of acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Phytochemical study ensured the presence of total phenolic contents (285.91 ± 0.75 mg of GAE/g of extract), total flavonoids (134.06 ± 0.63 mg of RE/g of extract), total tannins (149.60 ± 0.93 mg of TAE/g of extract) and free radical scavenging activity (IC50 value = 76.73 μg/ml found by DPPH method). Behavioral studies indicated that animals of GVII showed higher inflexion ratio (0.40 ± 0.03) for EPM, spent most of time (227.17 ± 2.13 s) in dark area of light dark test and had many hole pockings (39.83 ± 1.88) for hole board paradigm. Moreover, biochemical studies revealed that methanolic extract of L. stoechas (800 mg/kg/p.o.) significantly (P < 0.001) reduced brain AChE and MDA levels while improved SOD, CAT, and GSH levels. Thus the findings suggest that L. stoechas stabilizes memory by enhancing cholinergic neurotransmission and by providing defense against oxidative stress in mice brain.

Neuroprotective effect of Cubebin: A dibenzylbutyrolactone lignan on scopolamine-induced amnesia in mice.

Background & objectives:Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice.Methods:Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain.Results:Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC50 value of 992 μM. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and oxidative stress level.Interpretation & conclusions:Cubebin showed promising protective activity in scopolamine-induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity.

Sex and genetic differences in the effects of acute diesel exhaust exposure on inflammation and oxidative stress in mouse brain.

In addition to increased morbidity and mortality caused by respiratory and cardiovascular diseases, air pollution may also contribute to central nervous system (CNS) diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. DE contains more than 40 toxic air pollutants and is a major constituent of ambient particulate matter (PM), particularly of ultrafine-PM. Limited information suggests that exposure to DE may cause oxidative stress and neuroinflammation in the CNS. We hypothesized that males may be more susceptible than females to DE neurotoxicity, because of a lower level of expression of paraoxonase 2 (PON2), an intracellular anti-oxidant and anti-inflammatory enzyme. Acute exposure of C57BL/6 mice to DE (250-300μg/m3 for 6h) caused significant increases in lipid peroxidation and of pro-inflammatory cytokines (IL-1α, IL-1β, IL-3, IL-6, TNF-α) in various brain regions (particularly olfactory bulb and hippocampus). In a number of cases the observed effects were more pronounced in male than in female mice. DE exposure also caused microglia activation, as measured by increased Iba1 (ionized calcium-binding adapter molecule 1) expression, and of TSPO (translocator protein) binding. Mice heterozygotes for the modifier subunit of glutamate cysteine ligase (the limiting enzyme in glutathione biosynthesis; Gclm+/- mice) appeared to be significantly more susceptible to DE-induced neuroinflammation than wild type mice. These findings indicate that acute exposure to DE causes neuroinflammation and oxidative stress in brain, and suggest that sex and genetic background may play important roles in modulating susceptibility to DE neurotoxicity.

Enhanced neuroprotective effect of DHA and EPA-enriched phospholipids against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced oxidative stress in mice brain

The n-3 polyunsaturated fatty acids (PUFAs) are essential for brain and nervous system growth. The phospholipid forms of docosahexaenoic acid and eicosapentaenoic acid (DHA/EPA-PL) produce remarkable benefits regarding brain development and neurological function. This study investigated the effects of different n-3 PUFA formulations on brain oxidative injury induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Administration of MPTP (30 mg/kg, i.p., 7 days) induced movement disorder and altered the oxidant–antioxidant status of the brain by reducing intracellular GSH levels and antioxidant enzyme activities, and increasing intracellular lipid peroxidation. In comparison to fish oil (DHA/EPA-TG) and algae oil (DHA-TG), pretreatment with DHA/EPA-PL was more effective in preventing nerve oxidative stress and attenuating motor abnormalities. The anti-apoptosis effect of DHA/EPA-PL was superior to DHA-TG. Additionally, DHA/EPA-PL distinctly reduced the phosphorylation of p38 and Jun N-terminal kinase (JNK). The results indicate that DHA/EPA-PL could offer an efficient strategy to explore novel functional food for neuroprotection.

Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress

Current evidences support the inhibition of oxidative and inflammatory signaling mechanisms in the treatment of schizophrenia; as cure for this disease still remains limited. Doxycycline is a tetracycline antibiotic (a minocycline congener) with strong antioxidant and anti-inflammatory properties, and better pharmacokinetic profiles. Preclinical evidence indicates that minocycline possesses antipsychotic properties. This present study was designed to evaluate the effect of doxycycline on schizophrenia-like behaviors, as well as biomarkers of oxidative stress in mice brains. Novelty-induced rearing (NIR) behavior was used to evaluate the tranquilizing effect of doxycycline (25 - 200 mg/kg). The acute antipsychotic effects of doxycycline were assessed using apomorphine-induced stereotypy, ketamine-induced stereotypy, hyperlocomotion and enhanced immobility in forced swim test (FST). Catalepsy test was also employed to evaluate the extrapyramidal adverse effect of doxycycline in mice. The chronic antipsychotic effect of doxycycline was evaluated following oral administration of doxycycline in combination with ketamine (100 mg/kg) intraperitoneally for 10 days. Twenty four hours after the last administration, positive (locomotor activity), cognitive (Y-maze) and negative (FST) symptoms were assessed. Thereafter, levels of biomarkers of oxidative stress were evaluated in mice brains. Doxycycline significantly (P P P < 0.05) prevented the decrease in glutathione, and increased activities of superoxide dismutase and catalase in brain tissues. The results from this study suggest that doxycycline ameliorated schizophrenic-like behaviors via mechanisms related to attenuation of oxidative stress in mouse brain.

Combination of omega-3 Fatty acids, lithium, and aripiprazole reduces oxidative stress in brain of mice with mania.

Manic episode in bipolar disorder (BD) was evaluated in the present study with supplementation of omega-3 fatty acids in combination with aripiprazole and lithium on methylphenidate (MPD)-induced manic mice model. Administration of MPD 5 mg/kg bw intraperitoneally (i.p.) caused increase in oxidative stress in mice brain. To retract this effect, supplementation of omega-3 fatty acids 1.5 ml/kg (p.o.), aripiprazole 1.5 mg/kg bw (i.p.), and lithium 50 mg/kg bw (p.o) were given to mice. Omega-3 fatty acids alone and in combination with aripiprazole- and lithium-treated groups significantly reduced the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation products (thiobarbituric acid reactive substances) in the brain. MPD treatment significantly decreased the reduced glutathione (GSH) level and glutathione peroxidase (GPx) activity, and they were restored by supplementation of omega-3 fatty acids with aripiprazole and lithium. There is no remarkable difference in the effect of creatine kinase (CK) activity between MPD-induced manic model and the treatment groups. Therefore, our results demonstrate that oxidative stress imbalance and mild insignificant CK alterations induced by administration of MPD can be restored back to normal physiological levels through omega-3 fatty acids combined with lithium and aripiprazole that attributes to effective prevention against mania in adult male Swiss albino mice.

Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain.

Quercetin Protects Mouse Brain against Lead-Induced Neurotoxicity

Quercetin (QE), the major bioflavonoid in the human diet, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb)-induced neurotoxicity have not been clarified. The aim of the present study was to investigate the effects of QE on neurotoxicity in mice exposed to Pb. Mice were exposed to lead acetate (20 mg/kg body weight/day) intragastrically with or without QE (15 and 30 mg/kg body weight/day) coadministration for 3 months. The data showed that QE significantly prevented Pb-induced neurotoxicity in a dose-dependent manner. Exploration of the underlying mechanisms of QE action revealed that QE administration decreased Pb contents in blood (13.2, 19.1%) and brain (17.1, 20.0%). QE markedly increased NO production (39.1, 61.1%) and PKA activity (51.0, 57.8%) in brains of Pb-treated mice. Additionally, QE remarkably suppressed Pb-induced oxidative stress in mouse brain. Western blot analysis showed that QE increased the phosphorylations of Akt, CaMKII nNOS, eNOS, and CREB in brains of Pb-treated mice. The results suggest that QE can inhibit Pb-induced neurotoxicity and partly restore PKA, Akt, NOS, CaMKII, and CREB activities.

Protective effect of Cnestis ferruginea and its active constituent on scopolamine-induced memory impairment in mice: A behavioral and biochemical study

Context: Cnestis ferruginea Vahl ex DC (Connaraceae) (CF) is used in traditional African medicine in the management of CNS disorders. The degeneration and dysfunction of cholinergic neurons is closely associated with the cognitive deficits of Alzheimer’s disease (AD) and oxidative stress has been implicated in its pathogenesis. However, the influence of C. ferruginea on the cholinergic system and oxidative stress parameters has not been explored.Objective: The present study investigates the effect of methanol root extract of C. ferruginea and its active constituent amentoflavone (CF-2) on memory, oxidative stress and acetylcholinesterase (AChE) activity in scopolamine-induced amnesia.Materials and methods: Mice were orally treated with CF (25–200 mg/kg), CF-2 (6.25–25 mg/kg) for three days and memory impairment was induced by intraperitoneal injection of scopolamine (3 mg/kg). Memory function was evaluated by passive avoidance and Morris water maze tests. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain after the completion of behavioral studies.Results: Scopolamine caused memory impairment along with increased AChE activity and oxidative stress in mice brain. Oral administration of CF and CF-2 significantly prevented scopolamine-induced memory impairment, inhibited AChE and enhanced antioxidant enzyme activity in the brain following scopolamine injection as compared to vehicle administration in scopolamine (i.p.)-treated mice that were comparable to the effect of tacrine.Discussion and conclusion: The study demonstrated that C. ferruginea and its constituent have significant protective effect against scopolamine-induced memory deficits in mice that can be attributed to their antioxidant and antiAChE activity.

Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine.

Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice.

Myelophil ameliorates brain oxidative stress in mice subjected to restraint stress

We evaluated the pharmacological effects of Myelophil, a 30% ethanol extract of a mix of Astragali Radix and Salviae Radix, on oxidative stress-induced brain damage in mice caused by restraint stress. C57BL/6 male mice (eight weeks old) underwent daily oral administration of distilled water, Myelophil (25, 50, or 100mg/kg), or ascorbic acid (100mg/kg) 1h before induction of restraint stress, which involved 3h of immobilization per day for 21days. Nitric oxide levels, lipid peroxidation, activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione redox system enzymes), and concentrations of adrenaline, corticosterone, and interferon-γ, were measured in brain tissues and/or sera. Restraint stress-induced increases in nitric oxide levels (serum and brain tissues) and lipid peroxidation (brain tissues) were significantly attenuated by Myelophil treatment. Restraint stress moderately lowered total antioxidant capacity, catalase activity, glutathione content, and the activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase; all these responses were reversed by Myelophil. Myelophil significantly attenuated the elevated serum concentrations of adrenaline and corticosterone and restored serum and brain interferon-γ levels. Moreover, Myelophil normalized expression of the genes encoding monoamine oxidase A, catechol-O-methyltransferase, and phenylethanolamine N-methyltransferase, which was up-regulated by restraint stress in brain tissues. These results suggest that Myelophil has pharmacological properties protects brain tissues against stress-associated oxidative stress damage, perhaps in part through regulation of stress hormones.

Effect of hydroalcoholic extract of Vitex negundo Linn. leaves on learning and memory in normal and cognitive deficit mice

ObjectiveTo demonstrate the improvement in learning and memory by hydroalcoholic extract of Vitex negundo Linn. leaves (HEVN). MethodsThe leaves were macerated and percolated using 70 % ethanol to obtain dark green colored semisolid mass of HEVN. Effects of HEVN were evaluated in normal as well as in scopolamine- induced cognitive deficit mice paradigms using elevated plus maze (EPM) and object recognition test (ORT). Additionally, the effect of HEVN on acetyl-cholinesterase level (AchE) and oxidative stress in mice brain and in sodium nitrite induced respiratory arrest in mice was evaluated. ResultsPreliminary phytochemical analysis revealed the presence of alkaloids, flavonoids, proteins, and carbohydrates in the HEVN. Administration of HEVN (250 and 500 mg/kg/day, p.o.) for 8 days significantly increased inflexion ratio in EPM, discrimination index in ORT, and decreased brain AchE in both paradigms and prolonged the onset of time of death in sodium nitrite induced respiratory arrest in mice. Furthermore, HEVN (250, 500, and 1 000 mg/kg/day, p.o.) decreased brain lipid peroxidation and HEVN (500 and 1000 mg/kg/day, p.o.) increased brain reduced glutathione in scopolamine- induce cognitive deficit mice. ConclusionsThe present study revealed the effectiveness of HEVN in improving learning and memory processes in both paradigms. The effect might be due to AchE inhibition, antioxidant effect, and/or increase in cholinergic transmission.