title: The traditional drug Gongjin-Dan ameliorates chronic fatigue in a forced-stress mouse exercise model.
abstract: BACKGROUND
  Gongjin-Dan is a representative traditional Oriental medicine herbal drug that has been used to treat chronic fatigue symptoms for several hundred years. We evaluated the anti-fatigue effects of Gongjin-Dan and the underlying mechanisms in a chronic forced exercise mouse model.
  
  
  METHODS
  Balb/C male mice underwent an extreme treadmill-based running stress (1-h, 5 days/week), and daily oral administration of distilled water, Gongjin-Dan (100, 200, or 400 mg/kg), or ascorbic acid (100 mg/kg) for 28 days. The anti-fatigue effects of Gongjin-Dan were evaluated with behavioral tests (exercise tolerance and swimming tests), and the corresponding mechanisms were investigated based on oxidative stress and inflammatory cytokine and stress hormone levels in skeletal muscle, sera, and brain tissue.
  
  
  RESULTS
  Gongjin-Dan significantly increased exercise tolerance and latency times but reduced the number of electric shocks and immobilization time on the treadmill running and swimming tests, compared with the control group. Gongjin-Dan also significantly ameliorated alterations in oxidative stress-related biomarkers (reactive oxygen species and malondialdehyde), inflammatory cytokines (tumor necrosis factor-α, interleukin-1 beta, interleukin-6, and interferon-γ) and glycogen and L-lactate levels in skeletal muscle, compared with those in the control group. Moreover, Gongjin-Dan considerably normalized the forced running stress-induced changes in serum corticosterone and adrenaline levels, as well as brain serotonin level. These antioxidant and anti-stress effects of Gongjin-Dan were supported by the results of Western blotting (4-hydroxynonenal and heme oxygenase-1) and the gene expression levels (serotonin receptor and serotonin transporter).
  
  
  CONCLUSIONS
  These results support the clinical relevance of Gongjin-Dan regarding anti-chronic fatigue properties. The underlying mechanisms involve attenuation of oxidative and inflammatory reactions in muscle and regulation of the stress response through the hypothalmo-pituitary-adrenal axis.
authors: Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea.
authors: Sung-Shin
authors: SS
authors: Hong
authors: Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea.
authors: Ji-Young
authors: JY
authors: Lee
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daeheung-dong, Jung-gu, Daejeon 301-704, Republic of Korea.
authors: Jin-Seok
authors: JS
authors: Lee
authors: TKM-based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors: Hye-Won
authors: HW
authors: Lee
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daeheung-dong, Jung-gu, Daejeon 301-704, Republic of Korea.
authors: Hyeong-Geug
authors: HG
authors: Kim
authors: Department of Applied Chemistry, Oriental Medicine College of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon 300-716, Republic of Korea.
authors: Sam-Keun
authors: SK
authors: Lee
authors: Medical research division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors: Bong-Ki
authors: BK
authors: Park
authors: Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea. Electronic address: ckson@dju.ac.kr.
authors: Chang-Gue
authors: CG
authors: Son
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004597:Electroshock; D004837:Epinephrine / Q000097:blood; D005221:Fatigue / Q000188:drug therapy* / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D000447:Aldehydes; D016207:Cytokines; C546310:Gongjin-dan; D008565:Membrane Proteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D012701:Serotonin; D019344:Lactic Acid; D006003:Glycogen; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C027576:4-hydroxy-2-nonenal; D003345:Corticosterone; D004837:Epinephrine
keywords: Antioxidant; Chronic fatigue; Gongjin-Dan; HPA; Oxidative stress