Abstract
Background: Long-term exposure to chronic stress is thought to be a factor closely correlated with the development of metabolic disorders, such as diabetes mellitus and metabolic syndrome. Xiaoyaosan, a Chinese herbal formula, has been described in many previous studies to exert anxiolytic-like or antidepressant effects in chronically stressed rats. However, few studies have observed the effects of Xiaoyaosan on the metabolic disorders induced by chronic stress. Objective: We sought to investigate the effective regulation of Xiaoyaosan on 21-day chronic immobility stress (CIS, which is 3 h of restraint immobilization every day)-induced behavioural performance and metabolic responses and to further explore whether the effects of Xiaoyaosan were related to SHIP2 expression in the liver. Methods: Sixty male Sprague Dawley rats were randomly divided into a control group, a CIS group, a Xiaoyaosan group and a rosiglitazone group. The latter three groups were subjected to 21 days of CIS to generate the stress model. After 21 days of CIS, the effects of Xiaoyaosan on body weight, food intake, and behaviour in the open field test, the sucrose preference test and the forced swimming test were observed following chronic stress. Plasma insulin, cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) concentrations and blood glucose were examined, and the protein and mRNA expression levels of SHIP2, p85 and Akt in the liver were measured using RT-qPCR and immunohistochemical staining. Results: Rats exposed to CIS exhibited depression-like behaviours, decreased levels of plasma insulin, CHOL, LDL-C, TG and HDL-C, and increased blood glucose. Increased SHIP2 expression and reduced Akt, p-Akt and p85 expression were also observed in the liver. Xiaoyaosan exerted antidepressant effects and effectively reversed the changes caused by CIS. Conclusions: These results suggest that Xiaoyaosan attenuates depression-like behaviours and ameliorates stress-induced abnormal levels of insulin, blood glucose, CHOL, LDL-C and HDL-C in the plasma of stressed rats, which may be associated with the regulation of SHIP2 expression to enhance PI3K/Akt signalling activity in the liver.
Highlights
Epidemiological data have suggested that there are strong associations between chronic stress exposure and metabolic disease [1]
We explored the effects and potential mechanisms of Xiaoyaosan on stress-induced metabolic preliminarily evaluated the changes in body weight, food intake, plasma insulin, blood disorders
We investigated the effects of Xiaoyaosan on 21 days of chronic immobilization stress (CIS)-induced behavioural performance and metabolic responses and explored the potential mechanism underlying the regulatory effects in the liver
Summary
Epidemiological data have suggested that there are strong associations between chronic stress exposure and metabolic disease [1]. Acute restraint stress for 2 h [6], acute swimming stress [7], social protest stress [8] and chronic immobilization stress [9] caused significant increases in plasma corticosterone levels in male rats. Foot-shock stress and psychological stress increased the concentration of corticosterone, glucose, insulin, cholesterol and triglycerides in the plasma of male rats [10]. Few studies have observed the effects of Xiaoyaosan on the metabolic disorders induced by chronic stress. Methods: Sixty male Sprague Dawley rats were randomly divided into a control group, a CIS group, a Xiaoyaosan group and a rosiglitazone group. The latter three groups were subjected to 21 days of CIS to generate the stress model. Cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C)
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