sodium-nitrite and Memory-Disorders

Compounds that possess a pyrrolidone skeleton are a rich resource for the discovery of nootropic drugs. Oleracein E (OE), which possesses both tetrahydroisoquinoline and pyrrolidone skeletons, was first isolated from the medicinal plant Portulaca oleracea L. and was thought to be an active component in the cognition-improvement effect induced by this herb. The aim of this study was to investigate the effect of OE on cognitive impairment in senescent mice and its underlying mechanism of action.. Senescent Kunming mice were established by the intraperitoneal injection of D-galactose (D-gal, 1250 mg/kg/d) and NaNO2 (90 mg/kg/d) for 8 weeks. OE (3 mg/kg/d, 15 mg/kg/d) was orally administered for 8 weeks, and the nootropic drug piracetam (PA, 400 mg/kg/d) was used as a positive control. A Morris water maze was used to assess cognitive ability. GSH and MDA levels and T-AOC, SOD, and CAT activities in the brain or plasma were determined. Hippocampal morphology was observed by HE staining, and expression of the anti-apoptotic protein Bcl-2 and the pro-apoptotic proteins Bax and Caspase-3 was observed by immunohistochemical staining.. Large-dosage treatments with D-gal/NaNO2 for 8 weeks significantly reduced survival, impaired spatial memory capacity, compensatorily up-regulated GSH level and T-AOC and SOD activities, decreased CAT activity, and induced hippocampal neuronal damage and apoptosis as reflected by the apparent low expression of Bcl-2 and high expression of Bax and Caspase-3. OE significantly prolonged lifespan and was more potent than PA. Similar to PA, OE at 15 mg/kg/d improved memory capacity. The underlying mechanism of action was related to the reversal of abnormal brain antioxidant biomarkers (GSH, T-AOC, and SOD) to normal levels and the inhibition of hippocampal neuronal apoptosis.. OE from P. oleracea is an active compound for improving cognitive function and is also a candidate nootropic drug for the treatment of age-related dementia.

Topics: Alkaloids; Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cognition; Cognition Disorders; Galactose; Hippocampus; Male; Malondialdehyde; Maze Learning; Memory; Memory Disorders; Mice; Nootropic Agents; Phenols; Piracetam; Portulaca; Proto-Oncogene Proteins c-bcl-2; Sodium Nitrite; Superoxide Dismutase; Survival Rate

In Iranian traditional medicine, asafoetida is introduced as a valuable remedy for nervous disorders. Dementia was induced by injection of d-galactose and NaNO2 for 60 consecutive days. Animals were divided into normal control (NC), dementia control (DC), dementia prophylactic (DP), and dementia treated (DT). The learning and memory functions were examined by 1-way active and passive avoidance tests, using a shuttle box device. Avoidance response in training tests and 1 and 3 weeks later was significantly increased in NC, DP, and DT groups compared to the DC group. Step through latency in all groups was significantly greater than the DC group. Total time spent in light room, which shows the memory retention ability, in DP, NC, and DT was significantly greater than the DC group. Our findings indicate that asafoetida could prevent and treat amnesia. These beneficial effects maybe related to some constituent's effectiveness such as ferulic acid and umbelliferone.

Topics: Animals; Behavior, Animal; Dementia; Disease Models, Animal; Ferula; Food Preservatives; Galactose; Iran; Memory Disorders; Mice; Phytotherapy; Plant Preparations; Sodium Nitrite

The aim of this study was to investigate the protective effects of N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide (FLZ), a synthetic squamosamide cyclic derivative, on senescent mice induced by D: -galactose/NaNO(2) (120/90 mg/kg, i.p.) once daily for 60 days. FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D: -galactose/NaNO(2) treatment for 30 days. The cognitive function of mice was evaluated with step-down task. The brain biomarkers including monoamine oxidase B (MAO-B), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) were determined according to the manufacturer's instructions. The expression of acetylcholinesterase (ACh-E) and choline acetyltransferase (ChAT) protein in the CA1 region of hippocampus were counted by immunohistochemical staining. The results showed that the cognitive function, GSH-px activity in the brain, and the expression of ACh-E and ChAT in the CA1 region of hippocampus were significantly decreased, while MAO-B activity and MDA level in the brain were increased in senescent mice compared with the control mice. FLZ treatment prolonged the step-down latency and decreased the number of step-down errors in the senescent mice. In addition, FLZ treatment increased the GSH-px activity and the expression of ACh-E and ChAT in the hippocampus and decreased the MDA level and MAO-B activity compared with the senescent mice without drug administration. These findings suggested that FLZ improves the performance in the step-down task and the pathological alternations in senescent mice.

Topics: Aging; Animals; Avoidance Learning; Benzeneacetamides; Brain; Disease Models, Animal; Galactose; Glutathione Peroxidase; Male; Malondialdehyde; Memory Disorders; Mice; Mice, Inbred ICR; Monoamine Oxidase; Neurons; Neuroprotective Agents; Phenols; Sodium Nitrite

The aim of the present study was to access the protective effect of a novel synthesized squamosamide cyclic analogue, compound FLZ, on memory impairment in artificially senescent mice induced by chronic injection of D-galactose and sodium nitrite (NaNO(2)). Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO(2) (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO(2) injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO(2) induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO(2), indicating that FLZ is worth further studies for fighting antisenescence and dementia.

Topics: Administration, Oral; Aging; Animals; Annona; Benzeneacetamides; Blotting, Western; Dementia; Dose-Response Relationship, Drug; Galactose; Gene Expression Regulation; Glutathione Peroxidase; Hippocampus; Male; Malondialdehyde; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Microscopy; Phenols; Proto-Oncogene Proteins c-bcl-2; Sodium Nitrite; Superoxide Dismutase; Time Factors

The cholinergic system undergoes changes with aging and in Alzheimer's disease. The effects of the anticholinesterase drugs galantamine and donepezil were studied in a model with sodium nitrite-induced hypoxia in rats. The animals were trained in the shuttle-box active avoidance test and in step-through and step-down passive avoidance tests. In the active avoidance test, hypoxic rats showed a decrease in the number of avoidances in the learning session and in retention. The hypoxic rats receiving galantamine showed an increase in the number of avoidances during the learning session. The groups in hypoxia treated with donepezil had an increased number of avoidances in the learning session. In memory retention tests, significant differences were not observed in the hypoxic animals treated with galantamine or donepezil. In the step-through passive avoidance test, rats treated with galantamine had no change in the latency of reactions during the learning session and memory retention tests. In the step-down passive avoidance test, the animals treated with galantamine had increase latency of reactions during the learning and short- or long-memory retention tests. The hypoxic rats receiving donepezil had increased latency of reactions in the step-down short memory retention test. Our results suggest that galantamine and donepezil improve cognitive functions in a model of hypoxia.

Topics: Animals; Avoidance Learning; Cholinesterase Inhibitors; Disease Models, Animal; Donepezil; Dose-Response Relationship, Drug; Galantamine; Hypoxia, Brain; Indans; Male; Memory; Memory Disorders; Piperidines; Rats; Rats, Wistar; Sodium Nitrite; Time Factors

To study the anti-aging effects of Coeloglossum. viride (L) Hartm. var. bracteatum (Willd) Richter extract (CE) on senescent model mice induced by D-galactose and sodium nitrite.. After one week of accommodation, 60 female NIH mice were divided into six groups with 10 mice in each group: normal control group, aging model group, Piracetam (positive control) group [300 mg/ (kg x d)], and CE reatment groups [2.5, 5, and 10 mg/ (kg x d)]. Mice in aging model group, Piracetam group, and CE treatment group were consecutively intraperitoneally injected with D-galactose [120 mg/ (kg x d)] and sodium nitrite [90 mg/ (kg x d)] for 60 days. From day 47, mice in Piracetam group and CE treatment group were po given Piracetam 300 mg/ (kg x d) or CE 2.5, 5, and 10 mg/ (kg x d). Mice in normal control group and aging model group were po given saline. The drug administration lasted for 14 days. Water maze test was performed to evaluate the learning and memory function in the mice. The activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the activities of adenosinetriphosphatase (ATPase), and monoamine-oxidase (MAO) in brain tissue were measured.. The latencies in water maze test in aging model group mice were significantly longer than in normal control group (P < 0.01, P < 0.05), and the number of errors increased (P < 0.05). In aging model group mice, the activities of SOD, Na+K(+)-ATPase, and Ca2+Mg(2+)-ATPase decreased (P < 0.01, P < 0.05), while the content of MDA and the activities of MAO-A and MAO-B increased (P < 0.01). Piracetam [300 mg/ (kg x d), po] and CE [2.5, 5, 10 mg/ (kg x d), po] ameliorated the above changes in aging model mice.. CE may improve the memory dysfunction induced by consecutive injection of D-galactose and sodium nitrite,and has nootropic and antiaging effects.

Topics: Aging; Animals; Brain; Disease Models, Animal; Female; Galactose; Learning Disabilities; Malondialdehyde; Memory Disorders; Mice; Mice, Inbred Strains; Monoamine Oxidase; Orchidaceae; Oxidative Stress; Plant Extracts; Sodium Nitrite; Superoxide Dismutase

The study has shown that the extracts from leaves of Ginkgo biloba can significantly improve the NaNO2 and scopolamine induced impaired memory in mice. The potency of the ethanolic extract is greater than that of the aqueous extract. The ethanolic extract acts favorably on the memory function of normal animals. Both extracts help to prolong the survival time of mice receiving 200 mg/kg(ip)NaNO2.

Topics: Animals; Drugs, Chinese Herbal; Female; Lethal Dose 50; Male; Memory; Memory Disorders; Mice; Retention, Psychology; Sodium Nitrite