Myalgic encephalomyelitis/
chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression,
pain, and
fatigue. To date, the pathological mechanisms and
therapeutics remain uncertain. The purpose of this study was to investigate the effect of
myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression,
pain, and
fatigue behaviors and its underlying mechanisms.
Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression,
pain, and
fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal
hypersensitivity, and
fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and
transforming growth factor β (TGF-β) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized
calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased
tyrosine hydroxylase (TH) expression and the levels of
dopamine and
serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related
mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-β expression in the brain, as well as anti-inflammatory and
anti-oxidant mechanisms in internal organs.