title: BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.
abstract: Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain.
authors.affiliation: Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China; College of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. Electronic address: mjw98_2010@126.com.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Wang
authors.affiliation: Research Center for College of Basic Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China.
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Yang
authors.affiliation: Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China; College of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China.
authors.forename: Yue-Yue
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Research Center for College of Basic Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Niu
authors.affiliation: Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China.
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Feng
authors.affiliation: Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China.
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Wang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005518:Food Preferences; D005786:Gene Expression Regulation / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D057888:Iridoid Glucosides / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D057888:Iridoid Glucosides; C078040:catalpol; D013395:Sucrose; D051546:Cyclooxygenase 2; D020813:Receptor, trkB; D015232:Dinoprostone; D006854:Hydrocortisone
keywords: Antidepressant; Brain-derived neurotrophic factor; Catalpol; Chronic unpredictable mild stress; Cyclooxygenase-2