Browsing by Author "Benneth Ben-Azu"

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    Diosgenin reverses posttraumatic stress disorder in mice by augmenting neurochemical release and inhibiting HPA axis dysfunction, oxidative stress, and neuroinflammation
    (Journal of Affective Disorders Reports, 2024-07) Benneth Ben-Azu; Olusegun G. Adebayo; Adaeze Adebesin; Kenneth C. Oparaji; Vivian O. Ojiakor; Gift C. Pender; Bensandy O. Odeghe; Noah A. Omeiza; Abdulrahim Halimat A; Vivian Ezieshi; Glory Ighosotu; Emmanuel Omo-Odudu; Ekene I. Monye
    Post-traumatic stress disorder (PTSD) is a mental disorder linked to neurochemical, hypothalamic-pituitary- adrenal (HPA)-axis dysregulations, inflammatory and pro-oxidant challenges in response to traumatic events. It is one of the leading causes of neurocognitive declines, hence prompting the need for a pharmacological intervention. However, the impact of diosgenin, a naturally occurring steroidal saponin with adaptogenic-like action, on PTSD-induced neuropsychiatric disturbances and its underlying mechanisms are unknown. In this study, we investigated the outcome of diosgenin treatment in a multimodal traumatic, single prolonged stress (SPS)-induced PTSD in mice. Following the SPS-induced 7 days of PTSD, mice (n = 9) were thereafter treated with diosgenin (25 and 50 mg/kg) or fluoxetine (10 mg/kg) orally from days 8–20 (14 days). Locomotory, cognitive-, depressive- and anxiety-like behaviors were investigated. We assayed for changes in adrenal weight, serum glucose and corticosterone concentrations. Neurochemical, inflammatory, oxido-nitrergic dysfunctions and monoamine oxidase-B and acetylcholinesterase activities, were measured in the striatum, prefrontal-cortex and hippocampus. The results revealed that the SPS challenge inhibited locomotor, spatial/non-spatial memory functions, increased anxiety and depressive-like features, which were reversed by diosgenin. Diosgenin reduced SPS-induced increased monoamine oxidase-B, acetylcholinesterase activities, TNF-α, IL-6, malondialdehyde and nitrite levels in the striatum, prefrontal-cortex and hippocampus. Antioxidants such as glutathione, superoxide- dismutase, and catalase levels in SPS-mice brains were increased by diosgenin. Moreover, diosgenin attenuated SPS-induced hyper-HPA-axis mediation of PTSD by decreasing serum corticosterone, glucose levels and adrenal gland hypertrophy. Herewith, we suggest that diosgenin convenes adaptogenic-like protection against mice exposed to PTSD by enhancing antioxidant machinery, neurochemical modulations, and inhibition of oxido- nitrergic, inflammatory, and HPA-axis dysfunctions.
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    Mechanisms underpinning Carpolobia lutea G. Don ethanol extract’s neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia
    (Journal of Ethnopharmacology, 2023-01-30) Noah A Omeiza; Adewale Bakre; Benneth Ben-Azu; Abimbola A. Sowunmi; Abdulrahim Halimat A; Joseph Chimezie; Sodiq O Lawal; Olusegun G Adebayo; Abdullateef I Alagbonsi; Olugbenga Akinola; Amos O Abolaji; Adegbuyi O. Aderibigbe
    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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    Pretreatment with Carpolobia lutea ethanol extract prevents schizophrenia-like behavior in mice models of psychosis
    (Journal of Ethnopharmacology3 June 2022, 2022-06-03) Noah A. Omeiza; Adewale G. Bakre; Abdulrahim Halimat A.; Happy Isibor; Precious U. Ezurike; Abimbola A. Sowunmi; Benneth Ben-Azu; Adegbuyi O. Aderibigbe
    Ethnopharmacological relevance: Carpolobia lutea decoction is widely used as a phytotherapeutic against central nervous system-related disorders including insomnia, migraine headache, and mental illness in West and Central Tropical Africa. Aim: This study was designed to investigate the antipsychotic activity of Carpolobia lutea (EECL) in mice models of psychosis. Methods: Male Swiss mice (n = 5/group) were given EECL (100, 200, 400, and 800 mg/kg), haloperidol (1 mg/ kg), clozapine (5 mg/kg) and vehicle (10 mL/kg) orally before amphetamine (5 mg/kg)-induced hyper- locomotion and stereotypy, apomorphine (2 mg/kg)-induced stereotypy, or ketamine (10, 30, and 100 mg/kg)- induced hyperlocomotion, enhancement of immobility and cognitive impairment. Results: EECL (200, 400, and 800 mg/kg) prevented amphetamine- and apomorphine-induced stereotypies, as well as reduced hyperlocomotion induced by amphetamine and ketamine, all of which are predictors of positive symptoms. Regardless of the dose administered, EECL prevented the index of negative symptoms induced by ketamine. Furthermore, higher doses of EECL (400 and 800 mg/kg) also prevented ketamine-induced cognitive impairment, a behavioral phenotype of cognitive symptoms. Conclusion: Pretreatment with EECL demonstrated antipsychotic activity in mice, preventing amphetamine-, apomorphine-, and ketamine-induced schizophrenia-like symptoms, with 800 mg/kg being the most effective dose.