Mechanisms underpinning Carpolobia lutea G. Don ethanol extract’s neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia
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Date
2023-01-30
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Journal of Ethnopharmacology
Abstract
Ethnopharmacological relevance: Persistent ketamine insults to the central nervous system block NMDA receptors
and disrupt putative neurotransmission, oxido–nitrosative, and inflammatory pathways, resulting in
schizophrenia-like symptoms in animals. Previously, the ethnomedicinal benefits of Carpolobia lutea against
insomnia, migraine headache, and insanity has been documented, but the mechanisms of action remain
incomplete.
Aim of the study: Presently, we explored the neuro-therapeutic role of Carpolobia lutea ethanol extract (C. lutea) in
ketamine-induced schizophrenia-like symptoms in mice.
Materials and methods: Sixty-four male Swiss (22 ± 2 g) mice were randomly assigned into eight groups (n = 8/
group) and exposed to a reversal ketamine model of schizophrenia. For 14 days, either distilled water (10 mL/kg;
p.o.) or ketamine (20 mg/kg; i.p.) was administered, following possible reversal treatments with C. lutea (100,
200, 400, and 800 mg/kg; p.o.), haloperidol (1 mg/kg, p.o.), or clozapine (5 mg/kg; p.o.) beginning on days
8–14. During the experiment, a battery of behavioral characterizations defining schizophrenia-like symptoms
were obtained using ANY-maze software, followed by neurochemical, oxido-inflammatory and histological as-
sessments in the mice brains.
Results: A 7-day reversal treatment with C. lutea reversed predictors of positive, negative and cognitive symptoms
of schizophrenia. C. lutea also mitigated ketamine-induced neurochemical derangements as evidenced by mod-
ulations of dopamine, glutamate, norepinephrine and serotonin neurotransmission. Also, the increased acetyl-
cholinesterase activity, malondialdehyde nitrite, interleukin-6 and tumor necrosis-factor-α concentrations were
reversed by C. lutea accompanied with elevated levels of catalase, superoxide dismutase and reduced glutathione.
Furthermore, C. lutea reversed ketamine-induced neuronal alterations in the prefrontal cortex, hippocampus and
cerebellum sections of the brain.
Conclusion: These findings suggest that C. lutea reverses the cardinal symptoms of ketamine-induced schizo-
phrenia in a dose-dependent fashion by modulating the oxido-inflammatory and neurotransmitter-related
mechanisms.
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Antipsychotics C. lutea Ketamine Neurotransmitters Oxido-inflammation Schizophrenia