Influence of Xiaoyaosan on depressive-like behaviors in chronic stress-depressed rats through regulating tryptophan metabolism in hippocampus

Abstract

BackgroundTryptophan metabolism has always been considered to play a vital role in mental disorder diseases, and how traditional Chinese formula Xiaoyaosan regulates the tryptophan metabolism is a complement to the pathogenesis of depression. This study established a depression rat model by the chronic immobilization stress (CIS) method and observed the change in tryptophan metabolism in hippocampus and the effects of Xiaoyaosan.MethodsForty-eight male Sprague Dawley (SD) rats were randomly divided into the following four groups: control group, CIS group, Xiaoyaosan group, and fluoxetine group. The depression model was established by the 21-day CIS. The food intake and body weight were recorded, and the sucrose preference test (SPT), novelty suppressed feeding (NSF) test and open field test (OFT) were also used to evaluate the model. Then, the contents of tryptophan and 5-hydroxytryptamine (5-HT) in hippocampus were detected by the ELISA method, and the expression levels of tryptophan hydrogenase 2 (TPH2) and indoleamine 2,3-dioxygenase 1 (IDO1) in hippocampus were determined by quantitative reverse transcriptase polymerase chain reaction reaction (qRT-PCR) and Western blot methods.ResultsThe behavioral data showed a significant difference between the model group and the normal group. The 5-HT content in the hippocampi of CIS rats was significantly reduced, whereas the tryptophan content in the hippocampi of model rats was significantly increased. The TPH2 level in hippocampus of the model group was significantly decreased, and the IDO1 level was significantly increased. Xiaoyaosan and fluoxetine could significantly reverse these changes and had obvious curative effects.ConclusionThe abnormal tryptophan metabolism existed in the hippocampi of chronic stress-depressed rats, which was closely related to the pathogenesis of depression. Xiaoyaosan could improve the tryptophan metabolism by regulating the expression levels of TPH2 and IDO1, thus exerting an antidepressant-like effect.

Effect of Xiaoyaosan on Colon Morphology and Intestinal Permeability in Rats With Chronic Unpredictable Mild Stress

“…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). Our previous studies have confirmed that the dose of Xiaoyaosan based on dose conversion of an average adult body weight of 60 kg/d has an antidepressant effect on chronically stressed rats (Jiao et al, 2019). Therefore, according to the daily dosage for adults in clinical practice, the rats in the Xiaoyaosan group were treated with Xiaoyaosan at 2.224 g/kg/d for the intervention in this study.…”

The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats

“…Thus, our results showed that antidepressant treatment in stressed rats, compared with placebo, caused an increase in the mRNA expression of Tph2 in the cerebral cortex. Similarly, Jiao et al (2019) showed that chronic immobilization stress (CIS) decreased the mRNA and protein expression of Tph2 in the hippocampus, whereas fluoxetine normalized these effects.…”

“…Additionally, high protein expression of Ido1 may contribute to the inhibition of serotonin production (Myint et al 2007;Wichers et al 2005). Jiao et al (2019) found that CIS increases the level of mRNA and protein expression in the hippocampus and that these effects are normalized by fluoxetine. In turn, our results showed that venlafaxine treatment in stressed rats caused a reduction in Ido1 protein expression in the basal ganglia.…”

An Integrated Pharmacology-Based Analysis for Antidepressant Mechanism of Chinese Herbal Formula Xiao-Yao-San

“…Inflammatory cytokines may act as modulators of 5-HT (serotonin) receptors, and upregulate indoleamine 2,3dioxygenase (IDO), resulting in anxiety-like disorders (Myint and Kim, 2003). The antidepressant-like effects of XYS were associated with downregulation of peripheral IL-1β, IFNγ, TNF-α, and IL-6, and increased synthesis of tryptophan hydroxylase (TPH) and IDO, which play a role in promoting 5-HT synthesis (Jiao et al, 2019). XYS significantly inhibited TNF-α release in serum and the hippocampus through activation of the TNF-α/JAK2-STAT3 pathway, as shown in our preliminary study (Li et al, 2017).…”