Modulations in the ATPases during ketamine-induced schizophrenia and regulatory effect of “3-(3, 4-dimethoxy phenyl) -1- (4-methoxyphenyl) prop-2-en-1-one”: an in vivo and in silico studies

Abstract

Schizophrenia is a devastating illness and displays a wide range of psychotic symptoms. Accumulating evidence indicate impairment of bioenergetic pathways including energy storage and usage in the pathogenesis of schizophrenia. Although well-established synthetic drugs are being used for the management of schizophrenia, most of them have several adverse effects. Hence, natural products derived from medicinal plants represent a continuous major source for ethnomedicine-derived pharmaceuticals for different neurological disorders including schizophrenia. In the present study, we have investigated the neuroprotective effect of the novel bioactive compound i.e. “3-(3,4-dimethoxy phenyl) -1- (4-methoxyphenyl) prop-2-en-1-one” of Celastrus paniculata against ketamine-induced schizophrenia with particular reference to the activities of ATPase using in vivo and in silico methods. Ketamine-induced schizophrenia caused significant reduction in the activities of all three ATPases (Na⁺/K⁺, Ca²⁺ and Mg²⁺) in different regions of brain which reflects the decreased turnover of ATP, presumably due to the inhibition of oxidoreductase system and uncoupling of the same from the electron transport system. On par with the reference compound, clozapine, the activity levels of all three ATPases were restored to normal after pretreatment with the compound suggesting recovery of energy loss that was occurred during ketamine-induced schizophrenia. Besides, the compound has shown strong interaction and exhibited highest binding energies against all the three ATPases with a lowest inhibition constant value than the clozapine. The results of the present study clearly imply that the compound exhibit significant neuroprotective and antischizophrenic effect by modulating bioenergietic pathways that were altered during induced schizophrenia.

Keywords:

• Energy metabolism
• ATPases
• animal studies
• docking Studies
• schizophrenia

Acknowledgements

The authors are grateful to the Department of Zoology, Sri Venkateswara University for providing necessary facility to carry out this research work.

Disclosure statement

No potential conflict of interest was reported by the author(s).