title: Myelophil attenuates brain oxidative damage by modulating the hypothalamus-pituitary-adrenal (HPA) axis in a chronic cold-stress mouse model.
abstract: BACKGROUND
  Myelophil is composed of Astragali Radix and Salviae Miltiorrhizae Radix, according to the long traditional pharmacological practices, and it has been used for patients with chronic fatigue-associated symptoms including concentration problem or memory loss.
  
  
  OBJECTIVE
  This study aimed to evaluate the clinical relevance of Myelophil on brain oxidative damage using a chronic cold stress mice model.
  
  
  METHODS
  Balb/c mice were subjected to cold stress (4°C for 4h) six times per week for 2 weeks with or without oral administration of Myelophil (50, 100, or 200mg/kg), or ascorbic acid (50mg/kg).
  
  
  RESULTS
  Chronic cold stress induced histopathological hippocampal apoptosis with drastically increased serum levels of total reactive oxygen species and nitric oxide, as well as brain lipid peroxidation levels, protein carbonyl, and caspase-3/7 activity. These alterations were significantly ameliorated by Myelophil treatment. Myelophil administration significantly recovered the depleted glutathione and its enzymes, superoxide dismutase activity, and catalase protein and gene expression levels. Serum levels of corticosterone, dopamine, and adrenaline were notably altered by chronic cold stress but were significantly ameliorated by Myelophil treatment. Myelophil also normalized alterations in tumor necrosis factor-α, interleukin (IL)-1β, and IL-10 gene expression and protein levels. Chronic cold stress up-regulated gene expression levels of phenylethanolamine N-methyltransferase and monoamine oxidase-B, and glucocorticoid receptors in the hypothalamus and hippocampus, respectively, whereas Myelophil treatment completely normalized these levels.
  
  
  CONCLUSIONS
  These results suggest that Myelophil has potent pharmaceutical effects against chronic cold-stress-induced brain damage by relieving oxidative stress and inflammation and regulating stress hormones in mice.
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea.
authors.forename: Hyeong-Geug
authors.initials: HG
authors.lastname: Kim
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Han
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Choi
authors.forename: Seung-Wan
authors.initials: SW
authors.lastname: Son
authors.forename: Yong-Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Chang-Gue
authors.initials: CG
authors.lastname: Son
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology; D001930:Brain Injuries / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004298:Dopamine / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008995:Monoamine Oxidase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C543477:Astragali compound; D004365:Drugs, Chinese Herbal; C556062:IL10 protein, mouse; D053583:Interleukin-1beta; C530779:Myelophil; D017382:Reactive Oxygen Species; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase; D010625:Phenylethanolamine N-Methyltransferase; D053148:Caspase 3; D053179:Caspase 7; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine; D003345:Corticosterone; D004837:Epinephrine