title: Esculetin attenuates lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice.
abstract: Esculetin is one of the major bioactive compounds of Cichorium intybus L. The main purpose of the present study was to investigate the effects and possible underlying mechanism of esculetin (Esc) on lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice. Mice were pretreatment with esculetin (Esc, 20, 40mg/kg, intragastric administration) and a positive control drug fluoxetine (Flu, 20mg/kg, intragastric administration) once daily for 7 consecutive days. At the 7th day, LPS (0.83mg/kg) was intraperitoneal injection 30min after drug administration. Higher dose (40mg/kg) of esculetin and fluoxetine significantly decreased immobility time in TST and FST. There was no significant effect on locomotor activity in mice by the drugs. Esculetin significantly reduced LPS-induced elevated levels of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and hippocampus. Esculetin attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression by inhibiting nuclear factor-κB (NF-κB) pathway in hippocampus. In addition, neuroprotection of esculetin was attributed to the upregulations of Brain derived neurotrophic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) protein expression in hippocampus. The obtained results demonstrated that esculetin exhibited antidepressant-like effects which might be related to the inhibition of NF-κB pathway and the activation of BDNF/TrkB signaling.
authors.affiliation: Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Lingpeng
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Medical College of Soochow University, Suzhou 215000, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Nang
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Luo
authors.affiliation: Environmental Monitoring Station of Binhai, Zhongshizhonglu 105, Yancheng 224500, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Xiayun
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: He
authors.initials: H
authors.lastname: He
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
authors.forename: Jinglei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Central Laboratory, Nanjing Municipal Hospital of T.C.M., The Third Affiliated Hospital of Nanjing University of T.C.M., Nanjing 210001, China. Electronic address: hongyan3128@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Long
authors.affiliation: Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China. Electronic address: liuyuyaoda@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China. Electronic address: yantianhuabest@126.com.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003866:Depressive Disorder / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy*; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000627:therapeutic use; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014468:Umbelliferones / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D014468:Umbelliferones; D005473:Fluoxetine; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C007628:esculetin
keywords: Depression; Esculetin; Inflammation; Lipopolysaccharide