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1.
Hum Exp Toxicol ; 33(4): 369-82, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23900307

RESUMO

Biochanin-A (BCA), a potent phytoconstituent, has been previously used as an antitumour, a dopaminergic neuron protective agent, an antioxidant, an anticholinergic and on other pharmacological activities including neuroprotection. The present study was aimed to evaluate the behavioural and neurochemical evidence of BCA in cognitive-deficit mice in scopolamine challenged and natural aged-induced amnesia models in young and aged mice, respectively. BCA has exhibited decrease in the transfer latency and increase in step through latency significantly (p < 0.001) in scopolamine-treated and natural aged mice of exteroceptive behavioural models such as elevated plus maze and passive shock avoidance paradigm, respectively. A decrease in acetylcholinesterase activity of whole brain was seen in scopolamine and aged mice with standard piracetam (Pira; p < 0.001) and BCA in dose-dependent manner. The antioxidant property of BCA was proven by increase in GSH (p < 0.01) and decrease in thiobarbituric acid reactive substances level significantly in a scopolamine-challenged and aged mice. The scopolamine-treated mice exhibited significant (p < 0.01) increase in the content of noradrenalin and dopamine, which is a sign of dementia, and these excess increased neurotransmitters were reversed by BCA 40 mg kg(-1) (p < 0.05), BCA 20 mg kg(-1) (p > 0.05), BCA 10 mg kg(-1) (p < 0.05) and standard Pira (p < 0.05) when compared with scopolamine group. Furthermore, in histopathology of hippocampus, the Pira and BCA-treated mice were protected from the formation of pyknotic neurons, increases in the viable cells count and decreases in the number of degenerative cells compared with the scopolamine group. Hence, BCA could be potential enough for the betterment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Genisteína/uso terapêutico , Acetilcolinesterase/metabolismo , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Animais , Aminas Biogênicas/metabolismo , Encéfalo/enzimologia , Encéfalo/metabolismo , Transtornos Cognitivos/enzimologia , Transtornos Cognitivos/metabolismo , Modelos Animais de Doenças , Genisteína/farmacologia , Glutationa/metabolismo , Masculino , Camundongos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
2.
Pak J Biol Sci ; 16(23): 1687-97, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24506035

RESUMO

The aim of the study was to isolate the harmine alkaloids from the seeds of Peganum harmala (TAPH) and its cerebroprotective effect on cognitive deficit mice. The tested doses of TAPH were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models. The TAPH was found to be non-neurotoxic and Psychoactive by preventing the motor impairment and increasing the locomotion activity of animals in Rota rod and Actophotometer respectively. TAPH (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. In Elevated Plus Maze (EPM) and Passive Shock Avoidance paradigm (PSA) the TAPH shown improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transverse Latency Time (TLT) and increasing the Step Down Latency (SDL), respectively in dose dependent manner. The results were well supported by biochemical parameters, by inhibiting the Acetylcholinestrase (p < 0.01) activity, increasing the GSH (p < 0.001) level and decreasing the TBARS (p < 0.001) level of whole brain. Moreover TAPH has shown the significant Monoamine oxidase-A (MAO-A) inhibition action (p < 0.001), hence it reduces the metabolism of epinephrine, 5-HT and other monoamines and enhances the action of these neurotransmitters indirectly; this adrenergic system plays an important role in learning and memory. Further, TAPH (5 mg kg(-1)) protect the DNA fragmentation of frontotemporal cortex of the brain from hypoxic effect induced by Sodium nitrite in Gel Electrophoresis studies. The results were comparable to their respective standards. Hence, harmine alkaloids are potential enough to utilize in the management of Neurodegenerative disorders of the type Alzheimer's diseases.


Assuntos
Encéfalo/efeitos dos fármacos , Transtornos Cognitivos/prevenção & controle , Harmina/farmacologia , Hipóxia Encefálica/tratamento farmacológico , Degeneração Neural , Fármacos Neuroprotetores/farmacologia , Peganum , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Cognição/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Transtornos Cognitivos/psicologia , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol , Proteínas Ligadas por GPI/metabolismo , Glutationa/metabolismo , Harmina/isolamento & purificação , Hipóxia Encefálica/induzido quimicamente , Hipóxia Encefálica/metabolismo , Hipóxia Encefálica/patologia , Hipóxia Encefálica/psicologia , Masculino , Camundongos , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/isolamento & purificação , Peganum/química , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Tempo de Reação/efeitos dos fármacos , Sementes , Nitrito de Sódio , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
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