title: Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and 4-hydroxybenzyl alcohol, via the monoaminergic system and neuronal cytoskeletal remodeling.
abstract: BACKGROUND
  Gastrodia elata Blume is a highly valuable traditional Chinese medicine used in the treatment of depression. However, compounds with antidepressant effects in water extracts of G. elata Bl. (WGE) have not been identified. The aims of this study were to determine the major antidepressant compound in WGE and to evaluate the antidepressant effects of WGE and its active compounds which involved the monoaminergic system and neuronal cytoskeletal remodeling.
  
  
  METHODS
  Gastrodin (GAS) and 4-hydroxybenzyl alcohol (HBA) in WGE, were analyzed with high-performance liquid chromatography (HPLC)-ultraviolet detection. The forced swimming test (FST) was used to induce depression-like symptoms in 9 weeks old male Sprague-Dawley rats. The open field test (OFT) was used to measure anxiety after WGE, GAS, and HBA treatments. The levels of monoamine such as serotonin (5-HT), dopamine (DA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using HPLC-electrochemical detection. Western blotting was used to examine the 5-HT1A receptor and the neuronal cytoskeleton remodeling-related proteins, Slit, dihydropyrimidinase-related protein 2 (DPYSL2, also called CRMP2), Ras homologous member A (RhoA), and profilin 1 (PFN1) in vivo. Slit1 expression was evaluated in Hs683 cell line after treated with WGE (0.5mg/mL), GAS (50, 100 and 100μM), and HBA (50, 100 and 100μM).
  
  
  RESULTS
  Oral administration of WGE (500mg/kg bw), GAS (100mg/kg bw), and HBA (100mg/kg bw) exhibited the anti-depressant effect by significantly reducing the immobility time in FST, monoamine metabolism including the 5-HT to 5-HIAA in the hippocampus and DA to DOPAC and HVA ratios in the frontal cortex, amygdala, and hippocampus. In the hippocampus, the expression of the neuronal cytoskeleton remodeling-related negative regulators Slit1 and RhoA were significantly down-regulated. In addition, the positive regulators CRMP2 and PFN1 were significantly up-regulated following GAS, HBA, and WGE treatments. Moreover, WGE, GAS, and HBA were directly down-regulated Slit1 expression in Hs683 cells.
  
  
  CONCLUSIONS
  WGE, GAS, and HBA exhibited potential anti-depressant effects in rats by decreasing monoamine metabolism and modulated cytoskeleton remodeling-related protein expression in the Slit-Robo pathway. These results suggest that WGE can be used as agent for depressive prevention.
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Yi-Syuan
authors.initials: YS
authors.lastname: Lai
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Shih-Hang
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Lu
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Yu-En
authors.initials: YE
authors.lastname: Lin
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Suraphan
authors.initials: S
authors.lastname: Panyod
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, NJ 08901-8520, USA.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan; National Center for Food Safety Education and Research, National Taiwan University, Taipei 10617, Taiwan; Center for Food and Biomolecules, National Taiwan University, Taipei 10617, Taiwan. Electronic address: lysheen@ntu.edu.tw.
authors.forename: Lee-Yan
authors.initials: LY
authors.lastname: Sheen
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001592:Benzyl Alcohols / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D031668:Gastrodia; D005960:Glucosides / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D001592:Benzyl Alcohols; D005960:Glucosides; D010936:Plant Extracts; D015102:3,4-Dihydroxyphenylacetic Acid; D044282:Receptor, Serotonin, 5-HT1A; C018966:4-hydroxybenzyl alcohol; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C045345:gastrodin; D004298:Dopamine; D006719:Homovanillic Acid
keywords: 4-hydroxybenzyl alcohol; Anti-depressant; Forced swimming test; Gastrodia elata Blume; Gastrodin