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Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression.

Abstract：

:Oxido-inflammatory aberrations play a substantial role in the pathophysiology of depression. Oxido-inflammatory stress increases catabolism of tryptophan into kynurenine which leads to imbalance in kynurenine and serotonin levels in the brain. Naringenin a flavonoid, has been reported to possess antidepressant property by restoring serotonin and noradrenaline levels in the brain. Its effects on oxido-inflammatory aberrations in depression has not been investigated. With this background, the present study was designed to investigate the antidepressant-like potential of naringenin in olfactory bulbectomy (OBX)-induced neuroinflammation, oxidative stress, altered kynurenine pathway, and behavioural deficits in BALB/c mice. OBX-mice showed depression-like behavioural alterations characterized by hyperactivity in open field, increased immobility time in forced swim test and decreased sucrose preference. After 14 days, OBX-mice were treated by gavage with naringenin (25, 50 and 100 mg/kg) and fluoxetine (5 mg/kg) for two weeks. Naringenin significantly ameliorated depression-like behavioural alterations. Naringenin significantly restored corticosterone levels in serum and antioxidant enzymes (Catalase, SOD GSH), nitrite and MDA in cerebral cortex and hippocampus showing its anti-stress and antioxidant property. Naringenin also significantly decreased elevated pro-inflammatory cytokines like IL-1β, IL-6, TNF-α and NF-ҝβ levels. Naringenin also significantly increased neurotrophic growth factor like BDNF. Naringenin reversed altered levels of tryptophan, serotonin, 5-Hydroxyindole acetic acid and kynurenine in hippocampus and cortex. A positive correlation was found between KYN/TRP ratio and proinflammatory parameters while endogenous antioxidants were negatively correlated. In conclusion, naringenin showed potent neuroprotective effect in depression comparable to the fluoxetine by restoring alterations in kynurenine pathway via its antioxidant and anti-inflammatory potential.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Bansal Y,Singh R,Saroj P,Sodhi RK,Kuhad A

doi

10.1016/j.taap.2018.07.010

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

257-268

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(18)30321-1

journal_volume

355

pub_type

杂志文章

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Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression.