RESUMEN
Derangements of neuroimmune, neurotrophic and neurochemical homeostasis have important implications in psychosocial stress-induced psychopathologies. Whether quercetin, a neuroactive compound, protects against psychosocial stress-induced psychiatric disturbances particularly via neurochemical mechanisms remain less well elucidated. Therefore, we further investigated the putative neurochemical as well as other cellular mechanisms of quercetin on social-defeat stress (SDS) model of psychosocial impairments. Saline (10 mL/kg,i.p.), quercetin (25, 50 and 100 mg/kg,i.p.) and ginseng (50 mg/kg,i.p.) were given to intruder mice for 14 days. From days 7-14, ten minutes of aggressive-resident-induced SDS (physical and psychological) were conducted thirty minutes after treatments. Subsequently, behavioral assessments: open-field, light/dark board, Y-maze, novel-object recognition, social-interaction and tail-suspension tests were conducted on day 14. Adrenal weight and glucose levels were measured. Monoamines, brain-derived neurotrophic factor (BDNF), corticosterone, inflammatory cytokines (TNF-α, IL-6) and executioner caspase-3 concentrations were determined in specific brain regions by ELISA. Oxidative/nitrergic stress and cholinergic markers were determined with UV-spectrophotometry. Psychosocial stress-induced anxiety, depression and cognitive defects were improved by quercetin. The decreased serotonin in the prefrontal-cortex and dopamine in the striatum, elevated levels of noradrenaline and acetylcholinesterase in the prefrontal-cortex and hippocampus with corresponding decrease in BDNF were reversed by quercetin. Quercetin reduced SDS-induced increased neuronal inflammation, caspase-3 activity, malondialdehyde, nitrite levels, but increased antioxidant activities in the three brain regions. Adrenal hypertrophy, increased serum glucose and corticosterone release were reduced by quercetin. Our findings showed that quercetin attenuates psychosocial stress-induced passive coping behavior via normalization of HPA-axis, modulation of neurochemical release, enhancement of BDNF, and inhibition of brain oxidative/nitrergic stress, neuroinflammation and apoptotic pathway.
Asunto(s)
Acetilcolinesterasa , Quercetina , Acetilcolinesterasa/metabolismo , Adaptación Psicológica , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Ratones , Estrés Oxidativo , Quercetina/farmacología , Estrés Psicológico/metabolismoRESUMEN
Background In this study, the hematological and antioxidant potential as well as the osmotic fragility effects of a Nigerian polyherbal formulation were evaluated. Materials and methods A total of 40 fats were divided into four groups of 10 rats each. Group 1 served as the control group, and the rest were assigned increasing daily oral administration of the extract for 28 days. At the end of treatment, blood was collected for hematological and osmotic fragility studies. The free radical scavenging effect of the extract was investigated via different in vitro models as well. Results Results showed that the nitric oxide scavenging and 2,2-diphenyl-1-picrylhydrazyl (DPPH) activities of the extract were significant (p < 0.05) and compared favorably with that of vitamin C. At 200 and 400 µg/mL, the nitric oxide scavenging activities for Ajumbise Polyherbal Extract (APE) were 60.71 ± 0.25% and 59.49 ± 0.98%, respectively, whereas for the same concentrations of vitamin C, 74.60 ± 0.25% and 85.24 ± 0.14 scavenging activities were obtained. The (DPPH) activity at 100 µg/mL was 81.24 ± 0.02% for the extract and 96.22 ± 0.18% for vitamin C. However, at all concentrations, the extract had significantly lower Ferric Reducing Antioxidant Power (FRAP) activity than vitamin C. Red blood cell counts (RBCC), hemoglobin and packed cell volume values (PCV) were significantly lowered only in groups treated with 400 and 800 mg/kg of the extract (p < 0.05), whereas other RBCC parameters and white blood cell counts (WBCC) were not significantly affected (p < 0.05). Platelet (PLT) count was also significantly lowered in all extract-treated groups. The extract also significantly reduced RBCC percentage hemolysis (p < 0.05). Conclusions Ajumbise polyherbal may be free of hematoxicity and may improve the integrity of the RBC membrane due to its appreciable antioxidant activity.