chrysin and Memory-Disorders

Methotrexate (MTX) is a drug widely used for chemotherapy and can reduce cancer cell production by inhibiting dihydrofolate reductase and decreasing cancer cell growth. MTX has a neurotoxic effect on neural stem and glial cells, leading to memory deficits. Chrysin is a natural flavonoid that contains essential biological activities, such as neuroprotective and cognitive-improving properties. Therefore, the aim of the present study was to investigate the protective effect of chrysin against MTX-induced memory impairments related to hippocampal neurogenesis. Seventy-two male Sprague Dawley rats were divided into six groups: control, MTX, chrysin (10 and 30 mg/kg), and MTX+ chrysin (10 and 30 mg/kg) groups. Chrysin (10 and 30 mg/kg) was administered by oral gavage for 15 days. MTX (75 mg/kg) was administered by intravenous injection on days 8 and 15. Spatial and recognition memories were evaluated using the novel object location (NOL) and novel object recognition (NOR) tests, respectively. Moreover, cell proliferation, neuronal cell survival, and immature neurons in the subgranular zone of the hippocampal dentate gyrus were quantified by Ki-67, bromodeoxyuridine/neuronal nuclear protein (BrdU/NeuN), and doublecortin (DCX) immunohistochemistry staining. The results of the MTX group demonstrated that spatial and recognition memories were both impaired. Furthermore, cell division reduction, neuronal cell survival reduction, and immature neuron decreases were detected in the MTX group and not observed in the co-administration groups. Therefore, these results revealed that chrysin could alleviate memory and neurogenesis impairments in MTX-treated rats.

Topics: Animals; Bromodeoxyuridine; Cell Proliferation; Cell Survival; Cognition; Dentate Gyrus; Doublecortin Domain Proteins; Flavonoids; Hippocampus; Ki-67 Antigen; Male; Memory Disorders; Methotrexate; Neurogenesis; Neurons; Rats; Rats, Sprague-Dawley; Tetrahydrofolate Dehydrogenase

Hypothyroidism is a condition that affects multiple systems, including the central nervous system, causing, for example, cognitive deficits closely related to Alzheimer's disease. The flavonoid chrysin is a natural compound associated with neuronal improvement in several experimental models. Here, we evaluated the effect of chrysin on cognitive impairment in hypothyroid female mice by exploring neuroplasticity. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. On the 32nd day, the animals showed low plasma levels of thyroid hormones (hypothyroid mice) than the control group (euthyroid mice). Subsequently, mice were intragastrically administered with vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. At the end of the treatments, behavioral tests were performed: open-field test (OFT) and morris water maze (MWM). Then, the levels of neurotrophins (BDNF and NGF) in the hippocampus and prefrontal cortex were measured and tested the affinity of chrysin with neurotrophinergic receptors through molecular docking. Hypothyroid mice showed memory deficit in the MWM and reduced neurotrophins levels in the hippocampus and prefrontal cortex, meanwhile, the chrysin treatment was able to reversed the deficit of spatial memory function and increased the levels of BDNF in hipocamppus and NGF in both structures. Additionally, molecular docking analysis showed that chrysin potentially binds to the active site of the TrkA, TrkB, and p75NTR receptors. Together, these findings suggest that chrysin reversed behavioral and neurochemical alterations associated with memory deficit induced by hypothyroidism, possibly by modulating synaptic plasticity in the neurotrophinergic system.

Topics: Animals; Female; Flavonoids; Hippocampus; Hypothyroidism; Maze Learning; Memory Disorders; Mice; Molecular Docking Simulation

Stroke is devastating and a leading cause of morbidity and mortality worldwide. Cerebral ischemia-reperfusion and its subsequent reactive hyperemia lead to neuronal damage in the hippocampus and cognitive decline. Chrysin (5, 7-dihydroxyflavone) is a well-known member of the flavonoid family with antioxidant and neuroprotective effects. Therefore, in the present study, the aim was to investigate whether chrysin will be able to recover the brain function caused by ischemia-reperfusion (I/R) in rats. Adult male Wistar rats (250-300 g) were randomly divided into five groups: and submitted to cerebral I/R or a sham surgery after three-weeks of pretreatment with chrysin (CH; 10, 30 and 100 mg/kg; P.O.) and/or normal saline containing %5 DMSO. Subsequently, sensorimotor scores, cognition, local cerebral blood flow, extracellular single unit, and histological parameters were evaluated following I/R. Hippocampus was used to evaluate biomarkers including: oxidative stress parameters and prostaglandin E2 (PGE2) using ELISA kits. Data showed that pretreatment with chrysin significantly improved sensorimotor signs, passive avoidance memory, and attenuated reactive hyperemia, and increased the average number of spikes/bin (p < 0.001). Furthermore, chrysin pre-treatment significantly decreased the levels of MDA, NO, and PGE2 (p < 0. 001), while increased the levels of GPX and the number of surviving cells in the hippocampal CA1 region (p < 0.01, p < 0.001; respectively). This study demonstrates that chrysin may have beneficial effects in the treatment of cognitive impairment and help recover the brain dysfunction induced by I/R.

Topics: Animals; Cerebrovascular Circulation; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Flavonoids; Hyperemia; Male; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Random Allocation; Rats; Rats, Wistar

Cortical and hippocampal neuronal apoptosis and neuroinflammation are associated with behavioral deficits following traumatic brain injury (TBI).. The present study was designed to investigate the potential protective effects of flavonoid chrysin against TBI-induced vestibulomotor impairment, exploratory/locomotor dysfunctions, recognition memory decline, and anxiety/depression-like behaviors, as well as the verified possible involved mechanisms.. Chrysin (25, 50, or 100 mg/kg/day; P.O.) was administered to rats immediately after diffuse TBI induction, and it was continued for 3 or 14 days. Behavioral functions were assessed by employing standard behavioral paradigms at scheduled points in time. Three days post-TBI, inflammation status was assayed in both cerebral cortex and hippocampus using ELISA kits. Moreover, apoptosis and expression of Bcl-2 family proteins were examined by TUNEL staining and immunohistochemistry, respectively.. The results indicated that treatment with chrysin improved vestibulomotor dysfunction, ameliorated recognition memory deficit, and attenuated anxiety/depression-like behaviors in the rats with TBI. Chrysin treatment also modulated inflammation status, reduced apoptotic index, and regulated Bcl-2 family proteins expression in the brains of rats with TBI.. In conclusion, the results suggest that chrysin could be beneficial for protection against TBI-associated behavioral deficits, owing to its anti-apoptotic and anti-inflammatory properties.

Topics: Animals; Anxiety; Apoptosis; Brain; Brain Injuries, Traumatic; Depression; Flavonoids; Male; Memory Disorders; Rats; Rats, Wistar; Recognition, Psychology

Oxidative stress and apoptosis have major roles in the progression of traumatic brain injury (TBI)-associated motor and cognitive deficits. The present study was aimed to elucidate the putative effects of chrysin, a natural flavonoid compound, against TBI-induced motor and cognitive dysfunctions and possible involved mechanisms.. Chrysin (25, 50 or 100 mg/kg) was orally administered to rats starting immediately following TBI induction by Marmarou's weight-drop technique and continuously for 3 or 14 days. Neurological functions, motor coordination, learning and memory performances, histological changes, cell apoptosis, expression of pro- and anti-apoptotic proteins, and oxidative status were assayed at scheduled time points after experimental TBI.. The results indicated that treatment with chrysin improved learning and memory disabilities in passive avoidance task, and ameliorated motor coordination impairment in rotarod test after TBI. These beneficial effects were accompanied by increased the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), decreased malondialdehyde (MDA) content, prevented neuronal loss, diminished apoptotic index, elevated the expression of anti-apoptotic Bcl-2 protein, and reduced the expression of pro-apoptotic Bax protein in the cerebral cortex and hippocampus tissues.. Our findings suggest that both anti-oxidative and anti-apoptotic properties of chrysin (especially in the dose of 100 mg/kg) are possible mechanisms that improve cognitive/motor deficits and prevent neuronal cell death after TBI.

Topics: Administration, Oral; Animals; Antioxidants; Apoptosis; Brain; Brain Injuries, Traumatic; Disease Models, Animal; Flavonoids; Learning; Male; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Psychomotor Performance; Rats, Wistar

Chronic cerebral hypoperfusion, induced by permanent occlusion of bilateral common carotid arteries (2VO), is related to neurological disorders and contributes to cognitive decline. Chrysin (5,7-dihydroxyflavone) is an important member of the flavonoid family. The aim of this study is to investigate the effects of chrysin on cognitive deficits and brain damage in this rat 2VO model. At 52days after ligation, the escape latency in Morris water maze was significantly increased in rats subjected to 2VO, the neuronal damage was also increased accompanied by a large proliferation in glial fibrillary acidic protein (GFAP) immunoreactivity with marked white matter lesions, and neuronal cell apoptosis, all of which were significantly alleviated by long treatment of chrysin (30mg/kg). Biochemical examinations revealed that chrysin decreased lipid peroxide, reduced the increased activities of superoxide dismutase, and attenuated the decreased activities of glutathione peroxidase in 2VO rats. The results suggest that chrysin may have therapeutic potential for the treatment of neurodegeneration and dementia caused by decreased cerebral blood flow, which is most likely related, at least in part, to its anti-inflammatory and antioxidant properties.

Topics: Animals; Antioxidants; Apoptosis; Astrocytes; Brain; Brain Damage, Chronic; Brain Ischemia; Carotid Artery, Common; Cerebrovascular Circulation; Cognition Disorders; Dementia; Flavonoids; Glial Fibrillary Acidic Protein; Glutathione Peroxidase; Learning Disabilities; Lipid Peroxides; Male; Maze Learning; Memory Disorders; Neurons; Neuroprotective Agents; Rats; Rats, Wistar; Superoxide Dismutase