title: Ameliorating effects of gypenosides on chronic stress-induced anxiety disorders in mice.
abstract: BACKGROUND
  Ethanol extract from Gynostemma pentaphyllum (GP) shows anti-stress and anxiolytic functions in mice, and also protects dopamine neurons in 6-hydroxydopamine-lesioned rat model of Parkinson's disease. In addition, gypenosides (the gypenoside-enriched components of GP, GPS) have a protective effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. In this study, the ameliorating effects of GPS on chronic stress-induced anxiety disorders in mice were investigated.
  
  
  METHODS
  Mice were orally treated with GPS (100 and 200 mg/kg) once a day for 10 days, followed by exposure to electric footshock (EF) stress (0.6 mA, 1 s every 5 s, 3 min). After the final administration of either GPS, water extract of GP (GP-WX) or ethanol extract of GP (GP-EX, positive control), the behavioral tests such as elevated plus-maze, marble burying and locomotor activity tests, and the biochemical parameters including dopamine, serotonin and corticosterone levels, and c-Fos expression were examined.
  
  
  RESULTS
  Treatment with GPS (100 and 200 mg/kg) increased the number of open arm entries and the time spent on open arms in elevated plus-maze which were reduced by chronic EF stress. GPS (100 and 200 mg/kg) reduced the number of marbles buried which increased by chronic EF stress. In these states, the brain levels of dopamine and serotonin decreased by chronic EF stress and they were recovered by GPS. The serum levels of corticosterone increased by chronic EF stress were also reduced by GPS (100 and 200 mg/kg). Finally, chronic EF stress-induced c-Fos expression was markedly reduced by GPS (100 and 200 mg/kg) in the brain. GPS (100 and 200 mg/kg) also showed an equivalent efficacy on anxiolytic functions, as compared with GP-EX (50 mg/kg). However, GP-WX (50 mg/kg) showed a less effect on anxiety disorders than GP-EX (50 mg/kg) and GPS (100 and 200 mg/kg).
  
  
  CONCLUSIONS
  These results suggest that GPS (100 and 200 mg/kg) has anxiolytic effects on chronic EF stress-induced anxiety disorders by modulating dopamine and serotonin neuronal activities, c-Fos expression and corticosterone levels. GPS may serve as a phytonutrient in chronic stress-induced anxiety disorders.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea. t-t-zhao@hotmail.com.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Zhao
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea. wannaks@hanmail.net.
authors.forename: Keon Sung
authors.initials: KS
authors.lastname: Shin
authors.affiliation: Department of Food and Nutrition, Chungcheong University, Cheongju, Chungbuk, 28171, Republic of Korea. 6151494@hanmail.net.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea. myklee@chungbuk.ac.kr.
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects*; D029774:Gynostemma / Q000737:chemistry*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D010936:Plant Extracts; C474918:gypenoside