Abstract
Kidney-yang deficiency syndrome (KYDS) is a classic syndrome in traditional Chinese medicine, which is mainly caused by damage to the hypothalamic-pituitary-adrenal (HPA) axis. Hirsutella sinensis fungus (HSF), an artificial substitute of Cordyceps sinensis, has been widely used in TCM. However, the effects and the possible mechanism of HSF on the HPA axis and corresponding KYDS have not yet been investigated. In this study, Lewis rats were used as a spontaneous KYDS model. HSF was intragastrically administered to the Lewis rats at two doses: low dose (1 g/kg) and high dose (2 g/kg). Body weight, temperature, and behavioral tests including grip strength, open field, and Morris water maze (MWM) tests were used to evaluate the KYDS symptoms. Enzyme-linked immunosorbent assay was used to detect the level of circulating adrenocortisol (ACTH), corticosterone (CORT), corticotropin releasing hormone (CRH), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). In addition, mRNA expression of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin 10 (IL-10), CRH, glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) was detected by quantitative real-time polymerase chain reaction (Q-PCR). The Lewis rats were indicated to have KYDS symptoms and HSF treatment ameliorated these symptoms via enhancement of the HPA axis function, which was evidenced by the increased levels of CRH, ACTH, and CORT in serum and 17-OHCS in urine. HSF also significantly improved the expression of TNF-α, IFN-γ, and IL-2, secreted by Th1 cells, which might accelerate the activation of the immune system related to the HPA axis function. Thus, we conclude that HSF can alleviate KYDS symptoms in Lewis rats by regulating the HPA axis through accelerated immune system activation.
Highlights
Traditional Chinese medicine (TCM) employs a yin-yang balance as a conceptual framework of the human body; this is a crucial factor in controlling normal functions or homeostasis
Compared with the Wistar control group, the rectal temperature in the Lewis group was significantly lower than that in Wistar rats (P < 0.01); this is consistent with the clinical symptoms of Kidney-yang deficiency syndrome (KYDS). e rectal temperature of Hirsutella sinensis fungus (HSF) treatment groups had a similar dosedependent increasing trend compared with the Lewis control group, though there was no significant difference (P > 0.05, Figure 1)
Wistar control rat group; Lewis, Lewis control rat group; Lewis + L-HSF, Lewis rats administered a low dose of HSF (1 g/kg); and Lewis + H-HSF, Lewis rats administered a high dose of HSF (2 g/kg)
Summary
Traditional Chinese medicine (TCM) employs a yin-yang balance as a conceptual framework of the human body; this is a crucial factor in controlling normal functions or homeostasis. Kidney-yang deficiency syndrome (KYDS) is a classic syndrome in TCM. Damage to the hypothalamic-pituitary-adrenal (HPA) axis that includes the adrenal gland, thyroid, and gonads is the major pathological mechanism of KYDS [2, 3]. Lewis rats that displayed a decreased capacity of Evidence-Based Complementary and Alternative Medicine glucocorticoid receptors (GRs) in the pituitary gland, lower concentrations of corticotropin releasing hormone (CRH) messenger ribonucleic acid (mRNA) in the hypothalamus, fewer adrenocortical cells in a similar adrenal weight, and lower adrenocorticotropic hormone (ACTH) and corticosterone plasma levels than Wistar rats responded to a variety of stimuli [4]. Lewis rats are susceptible to experimental encephalomyelitis, rheumatoid arthritis, and other autoimmune diseases closely related to KYDS
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