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Metab Brain Dis. 2016 Oct;31(5):1011-21. doi: 10.1007/s11011-016-9839-5. Epub 2016 May 21.

The effects of fisetin on lipopolysaccharide-induced depressive-like behavior in mice.

Author information

1
Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China. yuxuefeng0527@126.com.
2
Zhejiang University Mingzhou Hospital, Zhejiang Province, 315000, China.
3
Department of Neurology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, Zhejiang Province, 315000, China.
4
Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China.
5
Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, China. wenzhoupan2003@163.com.

Abstract

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-1β, IL-6 and TNF-α) 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-κB 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.

KEYWORDS:

Fisetin; NF-κB; antidepressant; inflammation

PMID:
27209403
DOI:
10.1007/s11011-016-9839-5
[Indexed for MEDLINE]

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