Perturbations in the catecholamine metabolism and protective effect of '3-(3, 4-dimethoxy phenyl)-1-4(methoxy phenyl) prop-2-en-1-one' during ketamine-induced schizophrenia: an in vivo and in silico studies

Different kinds of secondary metabolites present in the medicinal plants play an important role to alleviate different human ailments including neurodegenerative disorders such as Parkinson's, Alzheimer's, epilepsy and schizophrenia etc. Recently we have isolated and characterized a novel bioactive compound viz. 3-(3,4-dimethoxy phenyl)-1-4(methoxy phenyl)prop-2-en-1-one from the methanolic extract of Celastrus paniculatus (CP) which has been widely used for the treatment of neurodegenerative diseases. The present investigation is mainly aimed to evaluate the neuroprotective potential of the above bioactive compound against ketamine-induced schizophrenia with particular reference to catecholaminergic metabolism using in vivo and in silico methods. Ketamine-induced schizophrenia caused significant elevation in biogenic amines (epinephrine, nor epinephrine, dopamine and 5-HT) and monoamine oxidase activity levels which were restored to normal during the treatment with the bioactive compound akin to the reference compound, clozapine. In addition, the compound has shown highest binding score against all the biogenic amine receptors viz. D1, D2, D3, D4 and serotonin receptor, 5-HT2A with lowest inhibition constant values than the reference compound, clozapine. The present findings suggest that modulation of CNS monoamine neurotransmitter system might partly contribute to the impairments associated with schizophrenia and the plant compound alleviates the monoaminergic abnormalities associated with the neurological dysfunction.Communicated by Ramaswamy H. Sarma.