Abstract
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 Salviae miltiorrhizae 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.
Highlights
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent state of helplessness due to overwork or mental illness that severely deteriorates physical, mental, and occupational quality, leading to social isolation [1]
We investigated the effects of MYP treatment on the major symptoms of ME/CFS, such as fatigue, depression, and pain behaviors, in a reserpine-induced mouse model
The number of buried marbles was significantly reduced on day 11 in all reserpineinjected groups compared to the CON group (RES: p < 0.01, RES + IMI5: p < 0.05, RES + IMI10: p < 0.001, RES + MYP50: p < 0.05, and RES + MYP100: p < 0.01 vs. CON group) (Supplementary Figure S1), and it was restored on day 22 only in the RES + MYP100 group (p < 0.05 vs. RES group) (Figure 2b)
Summary
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent state of helplessness due to overwork or mental illness that severely deteriorates physical, mental, and occupational quality, leading to social isolation [1]. ME/CFS patients have several unique traits compared to depression and fibromyalgia, including decreased serotonin (5-hydroxytryptamine, 5-HT) levels due to upregulation of the 5-HT transporter in astrocytes, which are reported to be related to autoimmune activity via an immune-inflammatory pathway [4]. Previous studies have reported that both oxidative stress and inflammatory cytokine levels were significantly altered in ME/CFS patients [5]. The reserpine-induced rodent model represents depression- and pain-like behaviors, and these behavioral changes are mainly associated with monoaminergic dysfunction related to dopamine and 5-HT uptake suppression [11]. Reserpine-induced animal models can be used as explanatory models of ME/CFS, targeting depression-, pain-, and fatigue-like behaviors and the associated pathological mechanisms [13,14]
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