Abstract
Chronic stress is a critical factor in the aetiology of anxiety disorders; however, in the clinic, enduring and preventive measures are not available, and therapeutic drugs are associated with inevitable side effects. Our study established an anxiety rat model using chronic restraint stress (CRS) and assessed these animals using the open-field test, elevated plus-maze test, and light-dark box test. Jie-Yu-He-Huan capsule (JYHH), a Chinese medicine formula, was used as a preventative drug. The HPA axis-mediated release of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone from the hypothalamus was tested. In the hippocampus and prefrontal cortex, concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid, as well as monoamine oxidase A, glucocorticoid receptor, and 5-HT1A receptor expression levels, were measured. Furthermore, we examined protein and mRNA expression of cAMP-PKA-CREB-BDNF pathway components. The results showed that JYHH had a significant preventative effect on the anxiety-like behaviour induced by CRS and prevented abnormal changes in the HPA axis and 5-HT system. Furthermore, CRS inhibited the cAMP-PKA-CREB-BDNF pathway, which returned to normal levels following JYHH treatment. This might be the underlying molecular mechanism of the antianxiety effect of JYHH, which could provide a new clinical target for preventative anxiolytic drugs for chronic stress.
Highlights
Stress is considered a normal physical and psychological reaction to positive or negative situations
0:0053, respectively), ACTH, and CORT concentrations. These results indicate that Jie-Yu-He-Huan capsule (JYHH) treatment could prevent the altered HPA axis hormone concentrations in serum caused by chronic restraint stress (CRS), similar to the effect of diazepam
The middle dose of JYHH prevented changes in the monoamine oxidase A (MAO-A) mRNA (p = 0:0163) and protein (p = 0:0480) levels in the hippocampus. These results indicate that high-dose JYHH treatment has a significant protective effect on the decreases in glucocorticoid receptor (GR) and 5-HT1AR and increases in MAO-A expression associated with CRSinduced anxiety
Summary
Stress is considered a normal physical and psychological reaction to positive or negative situations. Chronic stress is a critical factor in the aetiology of psychiatric diseases, such as anxiety disorders [1], and impacts behavioural, endocrine, and brain functions. With the continuous acceleration of the pace of life, the incidence of anxiety disorders is increasing. The first-line treatment of anxiety is benzodiazepines, but their long-term use can cause drug dependence and memory and cognitive impairment, increasing the risk of motor function damage and affecting its clinical application [3]. Traditional Chinese medicine has fewer side effects and strong individualization with high clinical research value [4]. It has attracted increasing attention for the treatment of anxiety
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