title: The effects of fisetin on lipopolysaccharide-induced depressive-like behavior in mice.
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.
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China. yuxuefeng0527@126.com.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yu
authors.affiliation: Zhejiang University Mingzhou Hospital, Zhejiang Province, 315000, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, Zhejiang Province, 315000, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China.
authors.forename: Lexing
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, Zhejiang Province, 315000, China.
authors.forename: Guokang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, China. wenzhoupan2003@163.com.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D044948:Flavonols; D019417:Hindlimb Suspension / Q000379:methods / Q000523:psychology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D013550:Swimming / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D044948:Flavonols; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C017875:fisetin
keywords: Fisetin; NF-κB; antidepressant; inflammation