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Involvement of anti-inflammatory, antioxidant, and BDNF up-regulating properties in the antipsychotic-like effect of the essential oil of Alpinia zerumbet in mice: a comparative study with olanzapine

Abstract

The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder’s cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we determined EAOZ effects in preventing and reversing schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. We conducted the behavioral evaluations of prepulse inhibition of the startle reflex (PPI), social interaction, and working memory (Y-maze task), and verified antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

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Data availability

Data will be made available under request.

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Acknowledgements

We thank the Brazilian Institutions, CNPq, CAPES, and FUNCAP for the financial support of this study.

Funding

Brazilian Institutions, CNPq, CAPES, and FUNCAP partially funded this study.

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FYRA, DFL, MOM, MEM – Designed the study

AJMCF, AMN, GVO, PXLG – treated the animals and performed behavioral tests

GSV, AJMCF, JC – Performed neurochemical determinations

DFL, DSM, FCFS – Performed statistical analysis of the data

DFL, DSM – constructed the graphics

FYRA, DSM, JC, AJMCF – Wrote the first draft of the manuscript

All authors approved the final version of the manuscript.

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Correspondence to Danielle S. Macedo.

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de Araújo, F.Y.R., Chaves Filho, A.J.M., Nunes, A.M. et al. Involvement of anti-inflammatory, antioxidant, and BDNF up-regulating properties in the antipsychotic-like effect of the essential oil of Alpinia zerumbet in mice: a comparative study with olanzapine. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00821-5

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Keywords

  • Schizophrenia
  • Ketamine model
  • Alpinia zerumbet
  • Anti-inflammatory effects
  • Antipsychotic effects
  • Extrapyramidal side effects