Effects of Xiaoyao San on exercise capacity and liver mitochondrial metabolomics in rat depression model / 中草药·英文版

OBJECTIVE@#This study aimed to investigate the therapeutic effects of Xiaoyao San (XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress (CUMS).@*METHODS@#A total of 24 male SD rats were randomly divided into four groups: control group (C), CUMS control group (M), Venlafaxine positive treatment group (V), and XYS treatment group (X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry (LC-MS) method. TCMSP database and GeneCards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed.@*RESULTS@#Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test, and retention time on the rotarod test (P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group (P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group. Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1β, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway.@*CONCLUSION@#XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.

Jiawei Xiaoyao San in treatment of anxiety disorder and anxiety: A review / 中草药·英文版

Jiawei Xiaoyao San (JWXYS) has shown excellent clinical efficacy in anxiety disorder, but has not yet attracted widespread attention. The animal experiments, clinical trials and mechanism studies of JWXYS were reviewed in this article, which may provide a reference for developing new anxiolytic drugs based on this prescription. The literature was searched in PubMed and CNKI and the documents written in English or with English abstracts were selected. JWXYS could reduce the anxiety symptoms of patients alone and reduce the adverse reactions when it is used in combination with other drugs in the clinic. In preclinical studies, JWXYS also showed therapeutic effects in reducing anxiety-like behavior. The mechanisms may include improving the hypothalamic-pituitaryadrenal (HPA) axis and hormone disorders, increasing neurotransmitter content, neurogenesis, and regulating the synthesis of related enzymes. This article shows that JWXYS could effectively treat anxiety disorders by regulating the central nervous system. In the future, with the participation of more researchers, it is expected to develop innovative drugs for the treatment of anxiety disorders based on JWXYS.

Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus / 中西医结合学报

OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Mechanism of Xiaoyao San in treatment of depression,breast hyperplasia,and functional dyspepsia based on network pharmacology / 中国中药杂志

This study aimed to explore the mechanism of Xiaoyao San(XYS) in the treatment of three diseases of liver depression and spleen deficiency, ie, depression, breast hyperplasia, and functional dyspepsia, and to provide a theoretical basis for the interpretation of the scientific connotation of "treating different diseases with the same method" of traditional Chinese medicines. Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active components of XYS which underwent principal component analysis(PCA) with the available drugs for these three diseases to determine the corresponding biological activities. The targets of XYS on depression, breast hyperplasia, and functional dyspepsia were obtained from GeneCards, TTD, CTD, and DrugBank databases. Cytoscape was used to plot the "individual herbal medicine-active components-potential targets" network. The resulting key targets were subjected to Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and gene ontology(GO) enrichment analysis. A total of 121 active components of XYS and 38 common targets in the treatment of depression, breast hyperplasia, and functional dyspepsia were collected. The key biological pathways were identified, including advanced glycation and products(AGEs)-receptor for advanced glycation and products(RAGE) signaling pathway in diabetic complications, HIF-1 signaling pathway, and cancer-related pathways. The key targets of XYS in the treatment of depression, breast hyperplasia, and functional dyspepsia included IL6, IL4, and TNF, and the key components were kaempferol, quercetin, aloe-emodin, etc. As revealed by the molecular docking, a strong affinity was observed between the key components and the key targets, which confirmed the results. The therapeutic efficacy of XYS in the treatment of diseases of liver depression and spleen deficiency was presumedly achieved by reducing the inflammatory reactions. The current findings are expected to provide novel research ideas and approaches to classify the scientific connotation of "treating different diseases with the same method" of Chinese medicines, as well as a theoretical basis for understanding the mechanism of XYS and exploring its clinical applications.

Protective effect and mechanism of Xiaoyao San on lipopolysaccharide-induced hippocampal neurons injury / 中国中药杂志

To investigate the relationship between anti-depressant effect and hippocampal nerve growth of Xiaoyao San,the inflammatory model of hippocampal neuron was induced by lipopolysaccharide( LPS). The effect of Xiaoyao San serum( final concentration of4%,8%) on the cell proliferation activity was detected by immunofluorescence,the levels of BDNF and β-NGF in the supernatant of hippocampal neurons were detected by ELISA,and the expressions of BDNF,NGF,Trk B,Trk A and CREB mRNA in cell lysate of hippocampal neuron were detected by PCR. Western blot was used to detect the expressions of Trk B,CREB,p-CREB and SYP protein in cell lysate of hippocampal neuron,and to reveal the neuroprotective effect and mechanism of Xiaoyao San. The results showed that8% Xiaoyao San serum could significantly increase in Brdu/Neu N ratio( P<0. 01). 4%,8% Xiaoyao San serum could significantly improve the levels of BDNF and β-NGF in supernatant( P<0. 05 or P<0. 01),up-regulate the expression of BDNF,NGF,Trk B,Trk A,CREB mRNA and Trk B,p-CREB,SYP protein in cell lysate( P< 0. 05 or P< 0. 01). 8% Xiaoyao San serum could significantly increase CREB protein in cell lysate( P<0. 05),and elevate in p-CREB/CREB ratio( P<0. 01). All the above results indicate that Xiaoyao San has a certain protective effect on LPS induced hippocampal neuron injury,which suggests that the protective effect of Xiaoyao San is related to the promotion of hippocampal nerve growth,which is one of its antidepressant mechanisms.

Analysis on endogenous metabolites in cecal tissue of CUMS-induced depression rats after Xiaoyao San intervention by GC-MS metabolomics / 中草药

Objective: To investigate the changes of endogenous metabolites in cecal tissue of CUMS-induced depression rat model interfered by Xiaoyao San via GC-MS metabolomics. Methods: Chronic unpredictable mild stress (CUMS) rat model was used and Xiaoyao San and fluoxetine hydrochloride (fluoxetine) treatment were intervention drug. The endogenous metabolites were analyzed and identified by NIST 05 database or authentic standards. The final data were introduced into SIMCA-P 13.0 software package for multivariate analysis. Results: The CUMS rat model was successfully duplicated, the metabolites of alanine, serine, and glutamic acid were reduced at fluoxetine group and Xiaoyao San group, and palmitic acid and stearic acid were increased in fluoxetine group in cecal tissue of rats after drug intervention, compared with model group with significant difference (P < 0.01 or 0.05). Conclusion: The endogenous metabolites were changed by Xiaoyao San intervention significantly in cecal tissue of CUMS rats, which provides a basis for further study of the mechanism of Xiaoyao San treatment of depression.

Mechanism Study of Xiaoyao San in Improving Depression-Like Behavior of Rats by Regulation of Hepatic Sinusoidal Endothelial Function / 广州中医药大学学报

Objective To observe the effectiveness and mechanism of Xiaoyao San (Xiaoyao Powder for Soothing Liver and Relieving Depression) in improving depression-like behavior of rats. Methods Male Wistar rats were randomized into normal group, model group, Xiaoyao San (1.9 g·kg-1·d-1) group, and fluoxetine (2 mg·kg-1·d-1) group. The rats were exposed to chronic unpredictable mild stress ( CUMS) to induce rat depression-like behavior. Field test was performed for the observation of effect of Xiaoyao San on rat depression-like behavior, Luminex liquid chip system was applied to detect the serum cytokines, and the amount and size of rat hepatic sinusoidal endothelial window were examined under electron microscope, and hepatic indoleamine 2, 3-dioxygenase ( IDO) and tryptophan 2, 3 -dioxygenaes ( TDO) expression levels were detected by immunohistochemical and Western blot methods. Results Xiaoyao San showed obvious effect on increasing sugar water consumption, the number of crossing the blocks and erection frequency in rats, decreasing serum levels of tumor necrosis factor alpha ( TNF-α) and interleukin 6 ( IL-6) , increasing the amount of hepatic sinusoidal endothelial window, promoting hepatic sinusoidal endothelial vascularization, and reducing TDO and IDO expression ( P<0.05 or P<0.01). Conclusion Xiaoyao San exerts obvious effect on improving rat depression-like behaviors, and the mechanism is probably related with the decrease of inflammatory factors, inhibition of IDO pathway, and improvement of hepatic sinusoidal endothelial function.

The Study on the Treatment of Ursodeoxycholic Acid Plus Xiaoyao San in Patients with Primary Intrahepatic Stones / 医学研究杂志

Objective To study the clinical therapeutic effectiveness on primary intrahepatic stones(PIS) treated by Ursodeoxycholic Acid(UDCA) combined with Xiaoyao San.Methods 90 cases of patients with PIS were randomly divided into two groups:the therapeutic group(n=60) and control group(n=30).The therapeutic group treated by UDCA combined with Xiaoyao San for 45 days.And the control group treated by UDCA alone.Then we observed the changes of symptoms as well as B-ultrasonic examine.Results The total effective rate was 86.7% in therapeutic group,higher than that in the control group,60%(P

Effect of Jiawei Xiaoyaosan on monoamine neurotransmitter in patients with psychological stress insomnia / 中华中医药杂志

0.05).Conclusions:The integrated medicine can regulate monoamine neurotransmitter to some extent.

Possible regulation channel of Xiaoyao San in treating rats of syndrome of liver invading the spleen by immunohistochemistry / 中华中医药杂志

Objective: Pervious RT-PCR results revealed the possibility of effective regulation channel of Xiaoyao San in treating rats of syndrome of liver invading the spleen. This experiment was designed to explore CIS rats’ immunohistochemistry findings in hippocampal subregion CA1 and amygdaloid subregion BLA after suppressing both amygdaloid AMPA receptors by microinjection of CNQX. To compare Xiaoyao San group with CNQX group, and to analysis of these findings may prove the possibility of effective regulation channel of Xiaoyao san treating this syndrome. Methods: 75 male SD rats were randomly divided into 5 equal groups: normal group, CIS group, sham-operation group, CNQX group and Xiaoyao San group. The number of GluR2 positive cells in hippocampal subregion CA1 and amygdaloid subregion BLA in these 5 groups were examined by immunohistochemistry test. Results: Compared with control group, the number of GluR2 positive cells decreased in hippocampal subregion CA1. Statistical analysis showed that no difference existed in control, CNQX and Xiaoyao San groups in CA1 region. Except CNQX group, tendency of changes were contradictory in BLA and CA1 region. In addition, the least in BLA in CNQX group. This finding revealed that Xiaoyao San may act the same as CNQX, thus Xiaoyao San afforded effective protection against this depression syndrome through suppression of both amygdaloid excitability. Conclusion: The balance coordination between hippocampus and amygdala may be the key in transformation from adaption to damage in a state of stress, was one of the central mechanisms of liver governing smoothing qi flow (LGSQF) on regulating the stress. Xiaoyao San may effectively regulate the balance of the excitability of hippocampus and amygdala. This hypothesis may reveal the regulation channel on Xiaoyao San affording effective protection against liver invading the spleen syndrome.

Effect of Dan Zhi Xiaoyao San and Its Extracts on Hypothalamus-Pituitary Gland-Adrenal Gland Secretion in Rats with Chronic Psychological Stress / 广州中医药大学学报

【Objective】To investigate the effects of Dan Zhi Xiaoyao San(DZXS) and its extracts on hypothalamic corticotropin releasing hormone(CRH) and plasma corticosterone(CORT) in rats with chronic psychological stress.【Methods】Wistar rats were randomized into 6 groups: A(normal control),B(model control),C (extract of DZXS extracted by water extraction and alcohol precipitation,3.608?g/kg),D(extract of DZXS extracted by petroleum ether,0.087?g/kg),E(extract of DZXS extracted by polysaccharide,2.20?g/kg) and F(DZXS 14.4?g/kg).Except group A,the rat models of chronic multi-phase psychological stress were established in other groups by improved Cart method.Groups A and B were given normal saline,and groups C,D and E were given the corresponding drugs according to the experimental design.Hypothalamic CRH and plasma CORT contents were examined to explore the therapeutic mechanism.【Results】Compared with group A,hypothalamic CRH and plasma CORT contents were increased in group B;hypothalamic CRH content was decreased in groups C,E and F(P

Experimental Study on Antianxietic Action of Xiaoyao San and Dan Zhi Xiaoyao San / 广州中医药大学学报

【Objective】To investigate the antianxietic action of Xiaoyao San(XS)and Dan Zhi Xiaoyao San(DZXS).【Methods】 Wistar rats were randomized into 5 groups: model control group,high-and low-dose DZXS groups(14.4?g/kg and 7.2?g/kg respectively),and high-and low-dose XS groups(21.06?g/kg and 10.53g/kg respectively).Social interaction test and open-field test were carried out to observe the antianxietic action of XS and DZXS.Except that the model group was given normal saline,the rats in other groups were given the corresponding drugs according to the experimental design for 14 successive days.After treatment,the activities within 5 min were monitored by two observers and then the mean value were calculated.【Results】High-and low-dose DZXS prolonged rats social interaction time and increased the times of body erection and dressing their hair,and low-dose XS also increased the times of body erection and dressing their hair(P