Brain Cholinesterase Research Articles

Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration

Chlorpyrifos is a extensively used organophosphate pesticide (OP). In this study, we closely looked into neurotoxicity of CPF and effect of vitamin B1, by checking the levels of cholinesterases, determining the activity of parameters of oxidative stress, inflammation and also level of apoptotic regulator. The study was performed on a total of 80 male Japanese quails (Coturnix japonica), (two control and 6 experimental groups, n = 10). Three group of quails were given by gavage chlorpyrifos (CPF) for 7 consecutive days at doses of 1.50 mg/kg b.w., 3.00 mg/kg b.w., and 6.00 mg/kg b.w. Another three groups were treated with 10 mg/kg b.w. of vitamin B1 i.m. 30 min after CPF application (in above mentioned doses). Our study have proved that all doses of CPF significantly inhibited cholinesterases in brain, while vitamin B1 reactivated them. CPF has led to an increase in the concentration of malondialdehyde (MDA), and activity of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), while tiamin changed the activity of antioxidant enzymes: CAT, SOD, GST. CPF stimulated apoptosis by decreasing B-cell lymphoma (Bcl-2) in brain, while application of vitamin B1 caused an increase of this parameter. CPF amplified inflammatory effect by elevating levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Thiamine proved its anti-inflammatory property by decreasing the expression of iNOS and interleukin-1(IL-1) and interleukin-6(IL-6). This study is highly pertinent because there is little defense currently available to humans and animals to prevent toxic effects of pesticides.

Methyl jasmonate reverses chronic stress-induced memory dysfunctions through modulation of monoaminergic neurotransmission, antioxidant defense system, and Nrf2 expressions.

Unpredictable chronic mild stress (UCMS) has been shown to cause memory loss via increased oxidative stress and deregulation of monoaminergic and cholinergic neurotransmissions. Although the benefits of methyl jasmonate (MJ), a well-known anti-stress plant hormone against chronic stress-induced psychopathologies, have been earlier reported, its effects on antioxidant defense molecules, monoaminergic transmitters, and nuclear factor erythroid 2-related factor 2 (Nrf2) immunopositive cells have not been extensively studied. The present study was designed to examine its effect on memory functions, antioxidant biomarkers, monoaminergic transmitters, and Nrf2 immunopositive cell expression in rats exposed to UCMS. Rats received an intraperitoneal injection of MJ (10, 25, and 50mg/kg) 30min before exposure to UCMS daily for 28days. Memory functionwas assessed on day 29 using a modified elevated plus maze and novel object recognition tests. The antioxidant biomarkers, level of monoamines (serotonin, noradrenaline, and dopamine), and Nrf2 immunopositive cell expression were determined in the rat brain tissues. The activity of cholinesterase and monoamine oxidase enzymes was also determined. MJ attenuated memory deficits and elevated the brain levels of monoamines in UCMS rats. UCMS-induced increase of brain cholinesterase and monoamine oxidase activities was inhibited by MJ. Also, MJ attenuated UCMS-induced decrease in antioxidant enzymes (CAT, GPx, GST, and SOD) and thiol contents in the brains of rats. UCMS-induced increase in NO level and Nrf2 immunopositive cell expression in the rat's brain was attenuated by MJ. Taken together, these findings suggest that increasing antioxidant defense molecules and monoaminergic/cholinergic neurotransmitters and decreasing the Nrf2 immunopositive cell expressions may contribute to the memory-promoting effects of MJ in rats exposed to UCMS.

Effect of diet supplemented with P. ostreatus and L. subnudus on memory index and key enzymes linked with Alzheimer's disease in streptozotocin-induced diabetes rats.

Mushrooms have been reported in folklore for the management of Alzheimer's disease (AD) and diabetes with limited scientific prove. This study aims to unravel the effect of diets supplemented with P. ostreatus and L. subnudus on diabetic encephalopathy (DE) in streptozotocin (STZ)-induced diabetic rats. The memory index, brain cholinesterase, arginase activity, and markers for oxidative stress were evaluated. STZ-induced diabetic rats exhibited memory deficits, elevated brain cholinesterase, arginase activity in comparison with nondiabetic rats. Also, markers for oxidative stress were altered in the brain of diabetic rat when compare with nondiabetic rats. Meanwhile, diabetic rats fed with supplemented-diets exhibited better memory index, reduced cholinesterase, arginase activity in comparison with untreated diabetic rats placed on a basal diet. Also, supplemented-diets restored altered markers of oxidative stress. Our findings indicated that P. ostreatus and L. subnudus-supplemented diets could prevent DE. Nevertheless, diets supplemented with L. subnudus had better nutraceutical potential than P. ostreatus. PRACTICAL APPLICATIONS: Diabetes mellitus is one of the most chronic diseases in the world. Also, it is a risk factor for several complications such as cognitive dysfunction, hypertension, and other health issues. Mushrooms are commonly consumed as food or as food supplements in many countries of the world and are a rich source of protein, chitin, and vitamins. Diet supplemented with P. ostreatus and L. subnudus were able to restore memory deficit in diabetic rats, proven to be a dietary intervention in the management of memory deficit linked with diabetes mellitus. Findings from this study show that consumption of P. ostreatus and L. subnudus as food or supplement could help in a diabetic state.

Anticholinesterase and Antioxidant Activities of Natural Abietane Diterpenoids with Molecular Docking Studies.

Alzheimer's Disease (AD) is one of the most prevalent causes of dementia in the world, and no drugs available that can provide a complete cure. Cholinergic neurons of the cerebral cortex of AD patients are lost due to increased activity of cholinesterase enzymes. Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) are the two major classes of cholinesterases in the mammalian brain. The involvement of oxidative stress in the progression of AD is known. Thus, the objective of this study is to determine strong ChE inhibitors with anti-oxidant activity. In this study, 41 abietane diterpenoids have been assayed for antioxidant and anticholinesterase (both for AChE and BuChE) properties in vitro, which were previously isolated from Salvia species, and structurally determined by spectroscopic methods, particularly intensive 1D- and 2DNMR and mass experiments. Molecular modeling studies were performed to rationalize the in vitro ChE inhibitory activity of several abietane diterpenoids compared with galantamine. Thirteen out of the tested 41 abietane diterpenoids exhibited at least 50% inhibition on either AChE or BuChE. The strongest inhibitory activity was obtained for Bractealine against BuChE (3.43 μM) and AChE (33.21 μM) while the most selective ligand was found to be Hypargenin E against BuChE enzyme (6.93 μM). A full correlation was not found between anticholinesterase and antioxidant activities. The results obtained from molecular modelling studies of Hypargenin E and Bractealine on AChE and BuChE were found to be in accordance with the in vitro anti-cholinesterase activity tests. Abietane diterpenoids are promising molecules for the treatment of mild-moderate AD.

Postmortem Evaluation of Reintroduced Migratory Whooping Cranes (Grus americana) in Eastern North America.

We reviewed necropsy records of 124 Whooping Cranes (Grus americana) recovered following reintroduction of 268 individuals from 2001 to 2016 in the eastern US. Causes of death were determined in 62% (77/124) of cases facilitated by active monitoring that limited decomposition and scavenging artifact. The greatest proportions of mortality were caused by predation (0.468; 95% confidence interval 0.356-0.580; 36/77), collision with power lines or vehicles (0.260; 0.162-0.358; 20/77), and gunshot (0.169; 0.085-0.253; 13/77). Six deaths were attributed to infection (0.078; 0.018-0.138; 6/77), including bacterial and fungal etiologies. Lead analysis of 50 liver samples yielded two results with elevated concentrations (3.65 and 10.97 ppm wet weight), and 10 bone samples from partial carcasses lacking suitable liver tissue resulted in one elevated result (48.82 ppm dry weight). These data indicate that underlying subclinical or clinical lead toxicosis may be a factor in up to 5% of deaths attributed to predation or impact trauma. Brain cholinesterase activity testing indicated no exposure to organophosphate or carbamate pesticides (mean±SD=17.32±2.90 µmol/min/g, 31/71). The causes of death and potential underlying factors summarized in this study constitute the first definitive mortality survey of migratory Whooping Cranes based on a high carcass recovery rate. Causes of death by infectious etiologies remained comparatively rare in this study, and occurred as single cases with no evidence of sustained transmission among reintroduced Whooping Cranes.

Difference in biochemical markers in the gibel carp (Carassius auratus gibelio) upstream and downstream of the hydropower plant

However the physiological stress in aquatic organisms associated with hydropower plants (HPP) ecosystems has been previously investigated, no studies have so far assessed it on biochemical level. Therefore this study evaluated an oxidative stress and toxicity in the gibel carp Carassius auratus gibelio associated with a small-scale HPP in the West Ukraine. A battery of liver, brain and blood markers was evaluated individuals inhabiting upstream and downstream of the dam of the small-scale Kasperivtci HPP (KHPP; an installed capacity of 7.5 MW), and from a reference site. Number of alterations were noted in fish from the KHPP impoundment facility including signs of oxidative stress (a decrease in superoxide dismutase (SOD) activity and an increase in protein carbonyls) and cytotoxicity (an increase in micronucleated erythrocytes and caspase-3 activity). No changes in DNA fragmentation in hepatocytes or brain cholinesterase activity were detected. As demonstrated by the integral stress index, fish associated with downstream of the dam revealed the greatest alterations reflected by the combined oppression of antioxidant system (SOD, catalase) and pro-oxidants (thiobarbituric acid reactive substances and oxyradicals), low concentration of metallothioneins, but high cathepsin D activity (as markers of lysosomal dysfunction and autophagy) and increased vitellogenin concentration in males (indicating an endocrine disruption). The study highlights that fish inhabiting ecosystems associated with HPP, particularly downstream of the dam, may face additional stresses with long-term effects yet to be evaluated.

Neurotoxicity of organophosphate pesticides could reduce the ability of fish to escape predation under low doses of exposure

Biomarkers are frequently used in ecotoxicology as they allow to study toxicant effects happening at low concentrations of exposure. However, most sublethal studies only evaluate cellular biomarkers which lack evident ecological relevance. We used a multibiomarker approach to estimate the toxic effects of ethoprophos, an organophosphate insecticide commonly used in banana plantations, on the tropical fish Astyanax aeneus (Characidae). We measured biomarkers at sub-individual (cellular) and individual (metabolism, behavior) levels and examined relationships among these responses. A sublethal exposure to ethoprophos caused a significant (54%) reduction of brain Cholinesterase (ChE) activity, reflecting the pesticide’s high neurotoxicity. However, other biomarkers like oxidative stress, biotransformation reactions, and resting metabolic rate were not affected. Exposure to ethoprophos modified antipredator behaviors such as escape response and detection avoidance (light/dark preference): exposed fish escaped slower from a simulated attack and preferred brighter areas in a novel tank. The relationship between ChE activity and reaction time suggests that pesticide-induced ChE inhibition reduces escape ability in fish. Our results provide evidence that impacts of organophosphate pesticides on fish ecological fitness can occur even with short exposures at very low concentrations.

Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems

Organophosphate pesticides are developmental neurotoxicants. We gave diazinon via osmotic minipumps implanted into dams prior to conception, with exposure continued into the second postnatal week, at doses (0.5 or 1 mg/kg/day) that did not produce detectable brain cholinesterase inhibition. We evaluated the impact on acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5HT) systems in brain regions from adolescence through full adulthood. Diazinon produced deficits in presynaptic ACh activity with regional and sex selectivity: cerebrocortical regions and the hippocampus were affected to a greater extent than were the striatum, midbrain or brainstem, and females were more sensitive than males. Diazinon also reduced nicotinic ACh receptors and 5HT1A receptors, with the same regional and sex preferences. These patterns were similar to those of diazinon given in a much more restricted period (postnatal day 1–4) but were of greater magnitude and consistency; this suggests that the brain is vulnerable to diazinon over a wide developmental window. Diazinon’s effects differed from those of the related organophosphate, chlorpyrifos, with regard to regional and sex selectivity, and more importantly, to the effects on receptors: chlorpyrifos upregulates nicotinic ACh receptors and 5HT receptors, effects that compensate for the presynaptic ACh deficits. Diazinon can thus be expected to have worse neurodevelopmental outcomes than chlorpyrifos. Further, the disparities between diazinon and chlorpyrifos indicate the problems of predicting the developmental neurotoxicity of organophosphates based on a single compound, and emphasize the inadequacy of cholinesterase inhibition as an index of safety.

DNA Damaging Effects, Oxidative Stress Responses and Cholinesterase Activity in Blood and Brain of Wistar Rats Exposed to Δ9-Tetrahydrocannabinol.

Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics of DNA breakage associated with THC exposure in white blood and brain cells of treated rats using the alkaline comet assay. The extent of oxidative stress after acute 24 h exposure to THC was also determined as well as changes in activities of plasma and brain cholinesterases (ChE) in THC-treated and control rats. The DNA of brain cells was more prone to breakage after THC treatment compared to DNA in white blood cells. Even though DNA damage quantified by the alkaline comet assay is subject to repair, its elevated level detected in the brain cells of THC-treated rats was reason for concern. Since neurons do not proliferate, increased levels of DNA damage present threats to these cells in terms of both viability and genome stability, while inefficient DNA repair might lead to their progressive loss. The present study contributes to existing knowledge with evidence that acute exposure to a high THC dose led to low-level DNA damage in white blood cells and brain cells of rats and induced oxidative stress in brain, but did not disturb ChE activities.

Characterisation of cholinesterase and histopathological features of brain of Clarias gariepinus following exposure to cadmium

Characterisation of cholinesterase and histopathological features of brain of Clarias gariepinus following exposure to cadmium

Antidepressants Modulate Behavioral, Biochemical, and Histological Alterations Induced by Chronic Aluminum Chloride Administration in Wistar Rats

Objective: To assess the effect of duloxetine and escitalopram on aluminum chloride (AlCl3)‑induced memory impairment in rats. Materials and Methods: Thirty rats were used. Group‑I (control) and Group‑II (toxic control) received 2% gum acacia, 10 mL/kg and AlCl3, 175 mg/kg, respectively. Group‑III (standard), Group‑IV, and Group‑V (test drug groups) received rivastigmine (1 mg/kg), duloxetine (10 mg/kg), and escitalopram (10 mg/kg), respectively, along with AlCl3, 175 mg/kg. All drugs and AlCl3 were administered orally daily for 2 months. The effect on cognition was assessed by Morris water maze (MWM). Brain acetylcholinesterase levels, oxidative stress parameters, and histology of the hippocampus were also evaluated. Results: Rats treated with only AlCl3 showed significant (P < 0.001) increase in latency during acquisition trials of day‑3 and day‑4 and decrease in percentage of both time spent and distance traveled in target zone during probe trial in MWM. Malondialdehyde was increased and glutathione decreased in the brain. Histopathology of the hippocampus showed unhealthy cellular architecture with a large number of degenerated cells. All these changes were significantly reversed in rivastigmine and test drug groups. Chronic administration of AlCl3 resulted in lowering of brain cholinesterase levels (P < 0.001) versus control. Cholinesterase levels were further significantly (P < 0.05) lowered in rats who received AlCl3 along with either rivastigmine or escitalopram. Conclusion: Escitalopram and duloxetine exerted a protective effect against AlCl3‑induced memory impairment in rats.

Cholinesterase inhibition in chicks treated with manganese chloride

The aim of the study was to examine the effect of manganese chloride in drinking water at 1 g/L on the plasma and brain chicks AChE activity in vivo and in vitro. At 14-day-old manganese caused significant decrease in the acetycholinestrase activity in the brain of chicks about 36%. While there was no significant inhibition in plasma AChE. Dichlorvos at 7 mg/kg, orally significantly inhibited plasma and brain AChE activity. Dichlorvos at 0.5 and 1 µl significantly inhibited plasma and brain cholinesterase activity in vitro, while manganese not affected on the cholinesterase activity in vitro. manganese with dichlorvos caused decrease in ration of AchE inhibited at 7 days old in brain and plasma AChE to 59% and 69% respectively, while increased in the ratio of inhibition at 14 days old in brain and plasma AChE activity of chicks to 64% and 91% respectively. The results suggested that manganese chloride caused decrease inhibition of AChE activity in brain of chicks manganese with dichlorvos causes decrease in the inhibited ratio of plasma and brain at 7 days old while causes increased the ratio of inhibition at 14 days old.

Anticholinergic and Hypocholesterolemic Activity of Juglan regia Improves Cognitive Functions in Mice

Backgroud: Walnut appears as the Signature of the Head and the kernel looks alike as the brain. It is a traditional belief that Walnuts may be beneficial to the brain. Objective: In the light of this traditional belief, the present study was conducted to confirm the effects of Juglan regia (Walnut) on cognitive functions of mice. Method: Two doses (500, 1000 mg/kg) of Walnut kernel powder were administered along with diet for fourteen successive days to Swiss young and aged mice. 29 groups of 145 Swiss young mice and 13 groups of 65 aged mice were employed in the present study. Exteroceptive behavioral models used in the present study were elevated plus maze and passive avoidance apparatus. Results: Decreased TL and increased SDL values were indicative of a significant improvement in the memory of young and aged mice after Walnut powder administration. It also reversed the memory deficits induced by scopolamine and diazepam. In addition, the brain cholinesterase activity in young and aged mice was significantly inhibited by Walnut at the dose of 500 mg/kg. Walnut also showed a notable reduction in total cholesterol levels to the limit of 20% in young and 14% in aged mice at the dose of 500 mg/kg. Enhanced acetylcholine levels resulting from diminished AChE activity and hypocholesterolemia produced by Walnut appear to be the underlying mechanism for the improved memory of mice. Keywords: Walnut, Akhrot, Juglan regia, hypocholesterolemia, cognitive functions, brain cholinesterase.

Efficacy of atropine sulfate/obidoxime chloride co-formulation against sarin exposure in guinea pigs

The efficacy and pharmacokinetics of the aqueous co-formulation contents of the Trobigard™ (atropine sulfate, obidoxime chloride) auto-injector were evaluated in a sarin exposed guinea pig model. Two subcutaneous (sc) sarin challenge doses were evaluated in guinea pigs instrumented with brain and heart electrodes for electroencephalogram (EEG) and electrocardiogram (ECG). Sarin challenge doses were chosen to reflect exposure subclasses with sublethal (moderate to severe clinical signs) and lethal consequences. The level of protection of intramuscular human equivalent doses of the co-formulation was defined by (1) the mitigation of signs and symptoms at a sublethal level and (2) the increase of survival time at the supralethal sarin dose levels.Pharmacokinetics of both atropine sulfate and obidoxime were proportional at 1 and 3 human equivalent doses, and only a small increase in heart rate was observed briefly as a side effect.At both sarin challenge doses, 54 μg/kg and 84 μg/kg, the co-formulation treatment was effective against sarin-induced effects. Survival rates were improved at both sarin challenge levels, whereas clinical signs and changes in EEG activity could not in all cases be effectively mitigated, in particular at the supralethal sarin challenge dose level. Reactivation of sarin inhibited cholinesterase was observed in blood, and higher brain cholinesterase activity levels were associated with a better clinical condition of the co-formulation treated animals.Although the results cannot be directly extrapolated to the human situation, pharmacokinetics and the effects over time related to plasma levels of therapeutics in a freely moving guinea pig could aid translational models and possibly improve prediction of efficacy in humans.

In Vitro Anti-cholinesterase and Cognitive Enhancing Properties of Essential Oils from Piper nigrum L. and Monodora myristica (Gaertn) Dunal

Aging in humans generally is associated with deterioration of cognitive abilities, particularly of learning and memory leading to dementia, including Alzheimer’s disease. A number of herbal medicines are reported to improve brain function and intelligence. In the present study, the ameliorating effects of essential oil extracted from Piper nigrum and Monodora myristica on learning and memory in Scopolamine induced amnesic mice were determined using two cognitive behavioural paradigms: the Step-Through Passive Avoidance and Morris-Water Maze test. Essential oils were obtained by hydro-distillation using a Clavenger-type apparatus and their profiles analyzed by GC-MS. Inhibitory effects on AChE and BuChE were investigated by Ellman’s method. The animals were assessed for performance by measuring the Step-Through Latency Time (SLT) and Escape Latency Time (ELT). Brain cholinesterase activities were assayed in brain tissues from the mice. The results showed that M. myristica and P. nigrum oils were characterized by 51 (94.76%) and 61 (90.65%) components, respectively. M. myristica is dominated by α-phellandrene (18.13%), while P. nigrum is dominated by β-pinene (5.92%) and caryophyllene (4.55%). Both oils at 416 µg/ml elicited significant inhibitory (p&gt;0.05) activity with M. myristica exhibiting a stronger inhibition against AChE and BuChE than P. nigrum. This trend was also exhibited significantly (p&gt;0.05) in both ELT and the SLT when compared to scopolamine-treated group. In conclusion, the seeds of M. myristica and P. nigrum are potential sources of active metabolites with anti-cholinesterase and cognition enhancing properties, but M. myristica exhibited a higher activity. Â

Oxime K074 – in vitro and in silico reactivation of acetylcholinesterase inhibited by nerve agents and pesticides

Oxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074.

Involvement of cholinesterases in oxidative stress induced by chlorpyrifos in the brain of Japanese quail

Chlorpyrifos is a widely used organophosphate pesticide (OP). In birds and mammals OP exhibits a toxic effect via inhibition of cholinesterases [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and through oxidative/nitrosative stress. In this study, the influence of chlorpyrifos on cholinesterase activity, parameters of oxidative stress [malondialdehyde (MDA); glutathione (GSH); superoxide dismutase (SOD); nitrite concentration (NO2−); hydrogen peroxide (H2 O2)], and inflammatory parameter [activity of myeloperoxidase (MPO)] in the brain of Japanese quail (Coturnix japanica) was examined. The study was conducted on a total of 60 male Japanese quails (one control and 5 experimental groups, n = 10), 3 to 4 wk old. Quails were administered by gavage chlorpyrifos (CPF) for 7 consecutive da at doses of 0.375 mg/kg BW, 0.75 mg/kg BW, 1.5 mg/kg BW, 3 mg/kg BW, and 6 mg/kg BW. Our studies have shown that all doses of CPF significantly inhibited both cholinesterases in brain: AChE from 22.74 to 37.83% and BChE from 19.53 to 61.9%, and that inhibition was dose dependent. Also, CPF has led to an increase in the concentration of MDA, GSH, NO2−, and H2 O2 and activity of SOD and MPO. Overall, these results support the hypothesis that CPF causes oxidative stress and inflammatory response. This research was carried out on quails because there is hardly any or not enough data about the neurotoxic effect of CPF and especially about its influence on oxidative stress in birds. This study is highly important because we are witnessing massive avian mortality in certain countries due to pesticides.

Capsicum Protects Against Rotenone-Induced Toxicity in Mice Brain Via Reduced Oxidative Stress and 5-Lipoxygenase Activation

Objective: Is to investigate the effect of Capsicum annuum L extract for its ability to prevent neuronal degeneration in rotenone intoxicated mice. Methods: Rotenone 1.5 mg/kg was subcutaneously given three times per week for two consecutive weeks. Starting from the first day of rotenone treatment, mice also received intraperitoneal injections of Capsicum extract (56 or 224 mg/kg). The brain and liver content of the lipid peroxidation product malondialdehyde (MDA), nitric oxide, reduced glutathione (GSH), paraoxonase 1 activity as well as brain cholinesterase and 5-lipoxygenase activities were determined. Histopathology and glial fibrillary acidic protein (GFAP) immunostaining in brain were also performed. Results: Rotenone treatment caused significantly raised brain and liver MDA by 64.4% and 93.3% and nitric oxide by 77.8% and 40.3%, respectively. Reduced glutathione decreased by 45.4% and 24.3% and PON1 activity fell by 39.4% and 28.7% in both the brain and liver, respectively. Cholinesterase activity in brain was inhibited by 60.6% while 5-lipoxygenase increased by 38.9%. In brain tissue, Capsicum prevented the increase in MDA and nitric oxide levels. Capsicum also restored GSH, PON-1 activity and alleviated the increase in 5-lipoxygenase activity. Cholinesterase activity was almost restored to control value by the higher dose of Capsicum. In the liver tissue, Capsicum caused a significant decrease in MDA, and nitric oxide levels, and increased GSH. It also increased PON-1 activity. The neurotoxicity of rotenone was prevented by the administration of Capsicum extract which prevented the neuronal degeneration and restored GFAP positive cells. Conclusions: Capsicum exerts a neuroprotective effect in rotenone intoxicated mice and this is likely to involve reduced oxidative stress and 5-lipoxygenase activation.

MEMORY ENHANCING ACTIVITY OF HYDROALCOHOLIC EXTRACT OF TERMINALIA CATAPPA LEAVES

The present study was to evaluate the effect of Terminalia catappa on cognitive functions and cholinesterase (ChE) activity in scopolamine-induced amnesia in rats. The extract of Terminalia catappa was administered orally at three doses (100, 200 and 300 mg/kg) for 7 and 14 consecutive days to the respective groups of rats. Piracetam (120 mg/kg) was used as a standard nootropic agent. Learning and memory parameters were evaluated using elevated plus maze (EPM) and passive avoidance. Brain cholinesterase activity was evaluated. It was observed that Terminalia catappa at the above- mentioned doses after 7 and 14 days of administration in the respective groups significantly reversed scopolamine (1 mg/kg i.p.)- induced amnesia, as evidenced by a decrease in the transfer latency in the EPM task and step-down latency in the passive avoidance task. Terminalia catappa reduced the brain ChE activity in rats.

Effect of pomegranate extracts on brain antioxidant markers and cholinesterase activity in high fat-high fructose diet induced obesity in rat model

BackgroundTo investigate beneficial effects of Pomegranate seeds oil (PSO), leaves (PL), juice (PJ) and (PP) on brain cholinesterase activity, brain oxidative stress and lipid profile in high-fat-high fructose diet (HFD) induced-obese rat.MethodsIn vitro and in vivo cholinesterase activity, brain oxidative status, body and brain weight and plasma lipid profile were measured in control rats, HFD-fed rats and HFD-fed rats treated by PSO, PL, PJ and PP.ResultsIn vitro study showed that PSO, PL, PP, PJ inhibited cholinesterase activity in dose dependant manner. PL extract displayed the highest inhibitory activity by IC50 of 151.85 mg/ml. For in vivo study, HFD regime induced a significant increase of cholinesterase activity in brain by 17.4% as compared to normal rats. However, the administration of PSO, PL, PJ and PP to HDF-rats decreased cholinesterase activity in brain respectively by 15.48%, 6.4%, 20% and 18.7% as compared to untreated HFD-rats. Moreover, HFD regime caused significant increase in brain stress, brain and body weight, and lipid profile disorders in blood. Furthermore, PSO, PL, PJ and PP modulated lipid profile in blood and prevented accumulation of lipid in brain and body evidenced by the decrease of their weights as compared to untreated HFD-rats. In addition administration of these extract protected brain from stress oxidant, evidenced by the decrease of malondialdehyde (MDA) and Protein carbonylation (PC) levels and the increase in superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels.ConclusionThese findings highlight the neuroprotective effects of pomegranate extracts and one of mechanisms is the inhibition of cholinesterase and the stimulation of antioxidant capacity.