Journal
METABOLIC BRAIN DISEASE
Volume 31, Issue 5, Pages 1011-1021Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11011-016-9839-5
Keywords
Fisetin; antidepressant; inflammation; NF-kappa B
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Funding
- Latitudinal project of Wenzhou Medical University [95012011]
- Natural Science Foundation of Zhejiang Province [Y14H310034]
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Major depressive disorder (MDD) involves a series of pathological changes including the inflammation and increased cytokine levels. Fisetin, a natural flavonoid, has anti-inflammatory and antioxidant, and also has been shown in our previous studies to exert anti-depressant-like properties. The present study aimed to investigate the effect of fisetin on lipopolysaccharide (LPS)-induced depressive-like behavior and inflammation in mice. The results suggested that the immobility time in the forced swimming test (FST) and tail suspension test (TST) were increased at 6 h, 12 h and 24 h after LPS injection (0.83 mg/kg). However, only the group of 24 h treatment did not show any effect on locomotion counts. Pretreatment with fisetin at doses of 20, 40 and 80 mg/kg (p.o.) for 7 days reversed LPS-induced alterations of the immobility time in both of these two tests. Further neurochemical assays suggested that pretreatment with fisetin reversed LPS-induced overexpression of pro-inflammatory cytokine (IL-1 beta, IL-6 and TNF-alpha) in the hippocampus and the prefrontal cortex (PFC). Moreover, higher dose of fisetin effectively antagonized iNOS mRNA expression and nitrite levels via the modulation of NF-kappa B in the hippocampus and PFC. Taken together, fisetin may be an effective therapeutic agent for LPS-induced depressive-like behaviors, which is due to its anti-inflammatory property.
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