Myelophil attenuates brain oxidative damage by modulating the hypothalamus-pituitary-adrenal (HPA) axis in a chronic cold-stress mouse model

• Published in: Journal of ethnopharmacology 2013-07, Vol.148 (2), p.505-514
• Main Authors: Kim, Hyeong-Geug, Lee, Jin-Seok, Han, Jong-Min, Lee, Jong-Seok, Choi, Min-Kyung, Son, Seung-Wan, Kim, Yong-Kyung, Son, Chang-Gue
• Format: Article
• Language: English
• Subjects: animal models; Animals; apoptosis; Apoptosis - drug effects; ascorbic acid; Ascorbic Acid - pharmacology; Brain damage; Brain Injuries - blood; Brain Injuries - drug therapy; Brain Injuries - metabolism; Caspase 3 - metabolism; Caspase 7 - metabolism; Chronic cold stress; cold stress; Corticosterone - blood; Disease Models, Animal; dopamine; Dopamine - blood; Drugs, Chinese Herbal - pharmacology; epinephrine; Epinephrine - blood; gene expression; glutathione; Glutathione - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - metabolism; hypothalamus; inflammation; interleukin-10; Interleukin-10 - metabolism; Interleukin-1beta - metabolism; lipid peroxidation; Lipid Peroxidation - drug effects; Male; memory; Mice; Mice, Inbred BALB C; Monoamine Oxidase - metabolism; Myelophil; necrosis; nitric oxide; Nitric Oxide - metabolism; oral administration; Oxidative stress; Oxidative Stress - drug effects; phenylethanolamine N-methyltransferase; Phenylethanolamine N-Methyltransferase - metabolism; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - metabolism; protein synthesis; reactive oxygen species; Reactive Oxygen Species - metabolism; receptors; Receptors, Glucocorticoid - metabolism; Salvia miltiorrhiza; superoxide dismutase; Superoxide Dismutase - metabolism; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2013.04.046

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. This study aimed to evaluate the clinical relevance of Myelophil on brain oxidative damage using a chronic cold stress mice model. 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). 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. 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. [Display omitted]