The Effect of Modified Qiyuan Paste on Mice with Low Immunity and Sleep Deprivation by Regulating GABA Nerve and Immune System

Abstract Background Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, rendering them more susceptible to the infiltration of pathogenic factors. LJC is obtained by modifing Qiyuan Paste, a traditional Chinese medicine formula for nourishing Yin and blood and calming the mind with a long history. Studies have shown that Dendrobium officinale can improve the immune function of sleep deprivation mice. Based on the traditional Chinese medicine (TCM) theory, LJC was prepared by adding Dendrobium officinale to Qiyuan Paste Decoction. Methods Yin deficiency syndrome indicators such as back temperature and grip strength of mice in each group were measured, and behavioral tests and pentobarbital sodium induced sleep test were performed. Automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA) kit and other methods were used to detect blood routine, serum immunoglobulin (IgG, IgA, and IgM), complement (C3, C4, and ACP) and LDH content in spleen, serum hemolysin and delayed hypersensitivity (DTH) levels. The serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected by high performance liquid chromatography (HPLC). Hematoxylin-eosin (H&E) staining and Nissl staining were used to evaluate the histological changes of hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expression of GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1, and the expression of CD4+ and CD8+ proteins in thymus and spleen tissues. Results Of note, LJC could prolong the sleep duration, improved the pathological changes of hippocampus, effectively up-regulated GABA content in the brain of mice, and down-regulated Glu content and Glu/GABA ratio, and increased the expression of GABRA1, GAT1, and GAD and decreased GABAT1 expression to improve sleep disorders. Importantly, LJC could improve the damaged thymus and spleen tissues of the model mice, and increase the activities of ACP and LDH in the spleen of the immunocompromised mice. At the same time, serum hemolysin levels, serum immunoglobulin IgG, IgA, and IgM levels increased after LJC administration , manifested as increased CD4+ content, decreased CD8+ content, and enhanced delayed-type hypersensitivity (DTH) response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes in blood, and decreased the percentage of neutrophils. Conclusions LJC can improve the model of immunocompromised mice with insufficient sleep. The mechanism may be to regulate the content of GABA/Glu and the expression levels of GABA metabolism pathway related proteins in the brain of mice, and enhance the specific and non-specific immune functions of mice.