Esculetin attenuates lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice.

Abstract:

:Esculetin is one of the major bioactive compounds of Cichorium intybus L. The main purpose of the present study was to investigate the effects and possible underlying mechanism of esculetin (Esc) on lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice. Mice were pretreatment with esculetin (Esc, 20, 40mg/kg, intragastric administration) and a positive control drug fluoxetine (Flu, 20mg/kg, intragastric administration) once daily for 7 consecutive days. At the 7th day, LPS (0.83mg/kg) was intraperitoneal injection 30min after drug administration. Higher dose (40mg/kg) of esculetin and fluoxetine significantly decreased immobility time in TST and FST. There was no significant effect on locomotor activity in mice by the drugs. Esculetin significantly reduced LPS-induced elevated levels of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and hippocampus. Esculetin attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression by inhibiting nuclear factor-κB (NF-κB) pathway in hippocampus. In addition, neuroprotection of esculetin was attributed to the upregulations of Brain derived neurotrophic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) protein expression in hippocampus. The obtained results demonstrated that esculetin exhibited antidepressant-like effects which might be related to the inhibition of NF-κB pathway and the activation of BDNF/TrkB signaling.

journal_name

Physiol Behav

journal_title

Physiology & behavior

authors

Zhu L,Nang C,Luo F,Pan H,Zhang K,Liu J,Zhou R,Gao J,Chang X,He H,Qiu Y,Wang J,Long H,Liu Y,Yan T

doi

10.1016/j.physbeh.2016.04.051

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

184-192

eissn

0031-9384

issn

1873-507X

pii

S0031-9384(16)30198-6

journal_volume

163

pub_type

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