Abstract
PurposeIn our present study, a rat depression model induced by 6 weeks of chronic unpredictable mild stress (CUMS) was established, and we investigated how Xiaoyaosan affects the intestinal permeability of depressed rats and alterations in tight-junction proteins (TJs) involved in this process.MethodsThe rat depression model was established using CUMS for 6 consecutive weeks. A total of 40 healthy male Sprague-Dawley rats were randomly sorted into four groups: the control group, CUMS group, Xiaoyaosan group, and fluoxetine group. All groups, excluding the control group, were subjected to the 6-week CUMS program to generate the depression model. Body weight, food intake, and behaviors were observed during the modeling period. Histopathological alterations of colon tissue were evaluated by hematoxylin-eosin staining (H&E), and mucus-containing goblet cells were detected by periodic acid-Schiff (PAS) staining. The ultrastructural morphology of colonic mucosa was observed by transmission electron microscopy. Furthermore, immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to determine the expression of TJs. The concentrations of 5-hydroxytryptamine (5-HT) in the hypothalamus and colon were also assessed using enzyme-linked immunosorbent assay (ELISA).ResultsTreatment of depressed rats with Xiaoyaosan alleviated depression-like behaviors as demonstrated by increases in the total distance traveled, the number of entries into the central area in the open field test, the duration spent in the central area, and sucrose preference. Xiaoyaosan treatment also increased body weight gain and food intake in depressed rats. Moreover, Xiaoyaosan treatment effectively improved the colonic pathological and ultrastructural changes, upregulated the expression of ZO-1, occludin, and claudin-1 in the colon, and increased 5-HT levels in the hypothalamus and colonic mucosa.ConclusionsXiaoyaosan treatment attenuates depression-like behaviors caused by CUMS and ameliorates CUMS-induced abnormal intestinal permeability, which may be associated with the expression of TJs. These results suggest that Xiaoyaosan exerts an antidepressant effect that may be related to an improvement of intestinal barrier function via the brain-gut axis.
Highlights
Depression is a common psychological or emotional disorder that is usually accompanied by a series of symptoms, including depressed mood, sleep disturbances, loss of interest in most activities (Ravina et al, 2006), low excitement for life, and even suicidal ideation (Lackamp et al, 2016)
A rat model of chronic unpredictable mild stress (CUMS) (Figure 1 and Table 1) was established in the present study, and the body weight and food intake of each rat were monitored weekly until the end of the CUMS program to verify whether the CUMS regimen affected these parameters
In the CUMS induction procedure, rats were successively exposed to a variety of mild stressors, mimicking the effect of chronic stress on promoting depression and inducing a number of long-term physical, behavioral, neurochemical, and neuroendocrine alterations similar to those observed in depressed patients (Liu et al, 2012)
Summary
Depression is a common psychological or emotional disorder that is usually accompanied by a series of symptoms, including depressed mood, sleep disturbances, loss of interest in most activities (Ravina et al, 2006), low excitement for life, and even suicidal ideation (Lackamp et al, 2016). Depression is a chronic and life-threatening mental disorder that affects almost 350 million people worldwide and leads to a substantial economic burden and considerable psychological pressure on families and society (Sobocki et al, 2006; Abe-Higuchi et al, 2016). Common adverse effects include withdrawal effects, sexual dysfunction, and weight gain (Rogers et al, 2013). Other adverse effects, such as feeling emotionally numb, sleep-related movement disorders, tremors, and abnormal bleeding (Cartwright et al, 2016), are common
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
