Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

Zhiyi Yan,Xiaojuan Li,Yueyun Liu,Youming Jiang,Qingyu Ma,Tingye Wang,Haiyan Jiao,Yajing Hou,Xiufang Ding,Jiaxu Chen,Qiuxia Pan

doi:10.3390/molecules23051073

Abstract

Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

Highlights

Depression is a common mental health problem in modern society, and one of its important inducing factors is the stress response, which is defined as an uncoordinated state of organism or the instability of the internal environment [1]
The observations to characterize the effects of Xiaoyaosan included the physical condition, food intake and body weight, and were carried out in mice with the aim of evaluating the efficacy of Xiaoyaosan in chronic unpredictable mild stress (CUMS)-induced mice
According to the results discussed in previous studies [21], our study showed the obvious antidepressant effect of Xiaoyaosan or fluoxetine according to the results of open fieldfield test test (OFT), sucrose preference test (SPT) and force swimming test (FST), anxiety-like behaviors, such as significant decrease in number of entries into central area of the OFT could be improved by the treatment

Summary

Introduction

Depression is a common mental health problem in modern society, and one of its important inducing factors is the stress response, which is defined as an uncoordinated state of organism or the instability of the internal environment [1]. The main characteristic of stress response is the hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and autonomic nervous system after stimulation by the internal and external environment [2]. Corticotropin-releasing factor (CRF) is a key factor in regulating the stress response, and the hypersecretion of CRF in the hypothalamus is the basis of HPA axis dysfunction [4]. The main sites of action of GC in the brain are the hippocampus and cerebral cortex, and excess GC can damage the brain by affecting the glucocorticoid receptor (GR) [6], while the excess of GC causes a negative feedback regulation in the dysfunction of the HPA axis, which leads to hyperactivity of the HPA axis [7]. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan

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Discussion

Conclusion