Journal
PHYSIOLOGY & BEHAVIOR
Volume 163, Issue -, Pages 184-192Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.physbeh.2016.04.051
Keywords
Esculetin; Lipopolysaccharide; Depression; Inflammation
Categories
Funding
- National Scientific & Technological major special Project significant creation of new drugs [2011ZX09102-002-01]
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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, 40 mg/kg, intragastric administration) and a positive control drug fluoxetine (Flu, 20 mg/kg, intragastric administration) once daily for 7 consecutive days. At the 7th day, LPS (0.83 mg/kg) was intraperitoneal injection 30 min after drug administration. Higher dose (40 mg/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-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in serum and hippocampus. Esculetin attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression by inhibiting nuclear factor-kappa B (NF-kappa B) 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-kappa B pathway and the activation of BDNF/TrkB signaling. (C) 2016 Elsevier Inc. All rights reserved.
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