title: Antidepressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress.
abstract: BACKGROUND
  Water extract of the fixed combination of Gardenia jasminoides Ellis fruit, Citrus aurantium L. fruit and Magnolia officinalis Rehd. et Wils. bark, traditional name - Zhi-Zi-Hou-Po (ZZHPD) is used for treatment of depressive-like symptoms in traditional Chinese medicine for centuries.
  
  
  OBJECTIVE
  The present study aimed to explore antidepressant-like effects and potential mechanisms of ZZHPD in a rat model of chronic unpredictable mild stress (CUMS).
  
  
  METHODS
  Antidepressant-like effects of ZZHPD were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system, neurotrophin and hippocampal neurogenesis.
  
  
  METHODS
  Antidepressant-like effects of ZZHPD (3.66, 7.32 and 14.64 g/kg/day) were estimated through coat state test, sucrose preference test, forced swimming test and open-field test. Effects of ZZHPD on hypothalamic-pituitary-adrenal (HPA) axis were evaluated by hormones measurement and dexamethasone suppression test. In addition, the expression of brain-derived neurotrophic factor (BDNF) in hippocampus was measured, as well as hippocampal neurogenesis was investigated by doublecortin (DCX) and 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN).
  
  
  RESULTS
  The results demonstrated that ZZHPD significantly reversed the depressive-like behaviors, normalized the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT), restored the negative feedback loop of HPA axis and improved the levels of BDNF, DCX and BrdU/NeuN compared with those in CUMS-induced rats.
  
  
  CONCLUSIONS
  The above results revealed that ZZHPD exerted antidepressant-like effects possibly by normalizing HPA axis function, increasing expression of BDNF in hippocampus and promoting hippocampal neurogenesis.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xing
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Shelby Interdisciplinary Biomedical Building, Room 777, 1825 University Blvd, Birmingham, AL 35294-0024, USA.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: cxh_syphu@hotmail.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002957:Citrus / Q000737:chemistry; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D032062:Gardenia / Q000737:chemistry; D006624:Hippocampus / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D039823:Iridoids / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D008297:Male; D015394:Molecular Structure; D055495:Neurogenesis / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D004365:Drugs, Chinese Herbal; D039823:Iridoids; D010936:Plant Extracts; C581916:Zhi-Zi-Hou-Pu decoction; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: Antidepressant; Chronic unpredictable mild stress; Hippocampal neurogenesis; Hypothalamic-pituitary-adrenal axis; Water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis