Metabolic Brain Disease

, Volume 31, Issue 5, pp 1011–1021 | Cite as

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

  • Xuefeng Yu
  • Xi Jiang
  • Xiangming Zhang
  • Ziwei Chen
  • Lexing Xu
  • Lei Chen
  • Guokang Wang
  • Jianchun Pan


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 antidepressant inflammation NF-κB 



Dr. Yu X.F and Jiang X contributed equally to this work. This work was funded by Latitudinal project of Wenzhou Medical University (No. 95012011) and Natural Science Foundation of Zhejiang Province (No. Y14H310034) for Professor J. C. Pan.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Xuefeng Yu
    • 1
  • Xi Jiang
    • 2
  • Xiangming Zhang
    • 3
  • Ziwei Chen
    • 1
  • Lexing Xu
    • 1
  • Lei Chen
    • 1
  • Guokang Wang
    • 1
  • Jianchun Pan
    • 4
  1. 1.Department of PharmacyZhejiang Pharmaceutical CollegeZhejiang ProvinceChina
  2. 2.Zhejiang University Mingzhou HospitalZhejiang ProvinceChina
  3. 3.Department of NeurologyNingbo Medical Treatment Center Lihuili HospitalNingboChina
  4. 4.Brain Institute, School of PharmacyWenzhou Medical UniversityWenzhouChina

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