Therapeutic potentiality of a new flavonoid against ketamine induced glutamatergic dysregulation in schizophrenia: In vivo and in silico approach - 16/04/21
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Abstract |
Glutamate and dopamine hypotheses are leading theories of the pathophysiology of schizophrenia. Multiple lines of evidence suggest that dopaminergic and glutamatergic dysfunction is an underlying mechanism in schizophrenia. Since currently available antipsychotic drugs have significant untoward side effects, identification of new neuroprotective compounds from the medicinal plants may prove beneficial in neurodegenerative disorders. In our previous investigation we have isolated, characterized and reported a novel bioactive compound viz. 3-(3, 4-dimethoxy phenyl)-1-(4-methoxy phenyl) prop-2-en-1-one from the Celastrus paniculatus (CP) is used for the current clinical intervention of schizophrenia disease. The present study is mainly aimed to evaluate the neuroprotective potential of the above bioactive compound against ketamine-induced schizophrenia with particular reference to glutamate metabolism using in vivo and in silico methods. The decrease in glutamine content and the activity levels of glutamate dehydrogenase, glutamine synthetase, and glutaminase in different regions of the rat brain suggests lowered oxidative deamination and lowered mobilization of glutamate towards glutamine formation during ketamine-induced schizophrenia. Pre-treatment with the plant compound reversed the alterations in glutamate metabolism and restored the normal glutamatergic neurotransmission akin to the reference drug, clozapine. In addition, the compound has shown strong interaction and exhibited the highest binding energies against selected NMDA receptors with the lowest inhibition constant than the reference drug. Recoveries of these parameters during anti-schizophrenic treatment suggest that administration of plant compound might offer neuroprotection by interrupting the pathological cascade of glutamatergic neurotransmission that occurs during schizophrenia.
El texto completo de este artículo está disponible en PDF.Highlights |
• | Novel bioactive compound of Celastrus paniculatus (CP) used for the treatment of Schizophrenia. |
• | Schizophrenia brain samples of different regions with glutamate metabolism validated by treating compound. |
• | NMDA receptors in silico studies with the maximum inhibition than the reference drug. |
Keywords : Glutamate metabolism, NMDA receptors, Animal studies, Molecular docking
Esquema
Vol 138
Artículo 111453- juin 2021 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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