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

Ethnopharmacological relevance

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.

Aim of the study

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

Material and methods

Balb/c mice were subjected to cold stress (4 °C for 4 h) six times per week for 2 weeks with or without oral administration of Myelophil (50, 100, or 200 mg/kg), or ascorbic acid (50 mg/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.