Mechanisms underpinning Carpolobia lutea G. Don ethanol extract's neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia.

Autor: Omeiza NA; Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria. Electronic address: omeizanoahadavize@gmail.com., Bakre A; Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria., Ben-Azu B; Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Nigeria., Sowunmi AA; Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria., Abdulrahim HA; Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Chimezie J; Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria., Lawal SO; Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria., Adebayo OG; Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria; Department of Physiology, Neurophysiology Unit, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, Port-Harcourt, Nigeria., Alagbonsi AI; Department of Clinical Biology (Physiology), School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Southern Province, Rwanda., Akinola O; Department of Pharmacology and Toxicology, Faculty of Pharmacy, College of Medicine, University of Ibadan, Nigeria., Abolaji AO; Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria., Aderibigbe AO; Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2023 Jan 30; Vol. 301, pp. 115767. Date of Electronic Publication: 2022 Oct 04.
DOI: 10.1016/j.jep.2022.115767
Abstrakt: 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 assessments 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 modulations of dopamine, glutamate, norepinephrine and serotonin neurotransmission. Also, the increased acetylcholinesterase 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 schizophrenia in a dose-dependent fashion by modulating the oxido-inflammatory and neurotransmitter-related mechanisms.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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