| Autor: |
Oladapo OM; Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria., Ben-Azu B; Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria. pharmben4ever@yahoo.com.; Department of Pharmacology, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, Port Harcourt, River States, Nigeria. pharmben4ever@yahoo.com., Ajayi AM; Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria., Emokpae O; Department of Pharmacology, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, Port Harcourt, River States, Nigeria., Eneni AO; Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria., Omogbiya IA; Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.; Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria., Iwalewa EO; Inflammatory and immunopharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria. |
| Abstrakt: |
Psychosocial stress has been widely reported to contribute to psychiatric disturbances. Perturbations in the enzymes of GABAergic and cholinergic systems have been implicated as precursors in different stress-related neuropsychiatric diseases. Targeting glutamic acid decarboxylase-67 kDa (GAD67) and acetylcholinesterase (AChE) via oxidative, nitrergic, and neuroinflammatory mechanisms have been recognized as prospective strategies for the prevention of psychosocial stress-induced behavioral impairments. Naringin, a neuro-active flavonoid compound isolated from citrus fruits, has been shown to produce memory-enhancing, antiepileptic, antidepressant, and anti-inflammatory activities similarly to ginseng, a very potent adaptogen. In this communication, we assessed the effect of naringin on social-defeat stress (SDS)-induced behavioral, GABAergic, cholinergic, oxidative, nitrergic, and neuroinflammatory changes in mice using the resident-intruder paradigm. The intruder male mice were culled into six groups. Groups 1 and 2 (normal- and SDS-controls) received sterile saline, groups 3-5 were given naringin (25-100 mg/kg, i.p.) whereas group 6 had ginseng (50 mg/kg, i.p.) daily for 14 days, but followed by 10 min SDS (physical and psychological) exposure to groups 2-6 with aggressor-resident mice. Behavioral effects using Y-maze, elevated-plus maze, sociability, and tail-suspension tests were assessed on day 14. GAD67, AChE enzymes, and biomarkers of oxidative, nitrergic, and neuroinflammatory changes were assayed in the striatum, prefrontal cortex, and hippocampus. Naringin and ginseng reversed all SDS-induced behavioral impairments. Naringin increased the levels of GAD67 and decreased AChE activities in the striatum, prefrontal cortex, and hippocampus. Furthermore, naringin reduced pro-inflammatory cytokines (TNF-α, IL-6), malondialdehyde, nitrite concentrations, and increased glutathione levels in a region-dependent manner. Our study suggests that naringin attenuated SDS-induced behavioral endophenotypes of neuropsychiatric disease through increased GAD67 synthesis, inhibition of AChE activity, oxidative, nitrergic stress, and neuroinflammatory processes in stress-sensitive brain regions. |
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