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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.

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Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China.
Zhejiang University Mingzhou Hospital, Zhejiang Province, 315000, China.
Department of Neurology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, Zhejiang Province, 315000, China.
Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China.
Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, China.


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.


Fisetin; NF-κB; antidepressant; inflammation

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