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Ethnopharmacological Relevance: Xiaoyaosan (XYS), a well-known formula for relieving depression, was originated from the book of "Taiping Huimin Heji Jufang" in Song Dynasty (960-1127 AD), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae with dose proportion of 6:6:6:6:6:3:2:2. It is commonly used for the treatment of depression-related syndromes in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure., Materials and Methods: An experimental despair animal model: the mice tail suspension test (TST) was used to evaluate the antidepressant activity of XYS and its fractions. GC-MS method was developed to identify the volatile components and determine 4 major volatile components in active fraction., Results: In the TST test, the effect of a low polar fraction (XY-EA) was superior to other fractions of XYS. 13 volatile compounds in the XY-EA were identified on the basis of standards, isolation and structural determination in our laboratory, NIST 05 database and literature data. The content of 4 major volatile compounds in XY-EA which is 6.703%., Conclusions: The petroleum ether fraction (XY-EA) appears to be the active fraction of XYS. 4 major components Z-ligustilide, palmitic acid, atractylenolide I, and atractylenolide II may be the antidepressant active compounds., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacology: Xiaoyaosan (XYS), a famous Chinese prescription, composed of Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.) Wolf), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Herba Menthae (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.), has been widely used in the clinic for treating mental disorders. Behavior and biochemical analyses indicate XYS has obvious anti-depression activity. However, there is no report on the effects of XYS using a metabolomics approach., Aim of the Study: Depression is a prevalent complex psychiatric disorder and its pathophysiological mechanism is not yet well understood. This paper was designed to study metabonomic characters of the depression induced by chronic unpredictable mild stress (CUMS) and the therapeutic effects of XYS, classic traditional Chinese medicine (TCM) in treating the depression., Material and Methods: A plasma metabonomics method based on gas chromatography/mass spectrometry (GC/MS) was developed. Principal component analysis (PCA) was utilized to classify and reveal the differences between the model group and control group. In turns, the concentration of these differences was analyzed with t-test to determine whether XYS was possible to influence the metabolic pattern induced by CUMS., Results: The significant difference in metabolic profiling was observed from model group compared with drug-dose group by using the PCA, indicating the recovery effect of XYS on CUMS rats. Some significantly changed metabolites like glycine, glucose and hexadecanoic acid have been identified. These biochemical changes are related to the disturbance in amino acid metabolism, energy metabolism and glycometabolism, which are helpful to further understand the CUMS and the therapeutic mechanism of XYS., Conclusions: Metabonomic approach is helpful to further understanding the pathophysiology of depression and assisting in clinical diagnosis of depression and is also a valuable tool for studying the essence of Chinese medicine's syndrome theory and therapeutic effect mechanism of TCM., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Xiaoyaosan (XYS), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae, is a valuable traditional Chinese medicine (TCM) which is used for the treatment of depression in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure. We divided the XYS into five different polar fractions, and explored the antidepressant activity of five different polar fractions to identify the active fraction., Materials and Methods: Behavior research and metabonomics method based on (1)H NMR were used for efficacy study of different fractions in chronic unpredictable mild stress (CUMS) model of depression. Rats were divided into 8 groups and drugs were administered during the 21 days model building period. The urine samples of rats were collected overnight (12h) on 21 day and the metabolic profiling of the urine was measured using NMR. Multivariate analysis was also utilized to evaluate the active fraction of XYS., Results: In the behavior research, there were significant difference between the lipophilic fraction group (XY-A) and the model group. In addition, with pattern recognition analysis of urinary metabolites, the results showed a clear separation of the model group and control group, while XY-A group was much closer to the control group in the OSC-PLS score plot. Seven endogenous metabolites contributing to the separation of the model group and control group were detected, while XY-A group regulated the 5 perturbed metabolites showing a tendency of recovering to control group., Conclusions: The present work suggested that petroleum ether fraction was the most effective fraction, implying that lipophilic components contribute to the antidepressant effect of XYS., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacology: Xiaoyaosan, a famous Chinese prescription, composed of Poria (Poria cocos (Schw.) Wolf), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Herba Menthae (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.), has been widely used in the clinic for treating mental disorders. Behavior and biochemical analyses indicate xiaoyaosan has obvious anti-depression activity. However, there is no report on the effects of xiaoyaosan using a metabolomics approach., Aim of the Study: A urinary metabolomics method was applied to evaluate the efficacy of xiaoyaosan on rat model of chronic unpredictable mild stress., Material and Methods: Rats were divided into 6 groups and drugs were administered during the 21-day model building period. Urine was measured using GC-MS, processed with XCMS and Microsoft Excel and analyzed by SIMCA-P and SPASS software. Variable importance in projection statistics and loading plot were used to find biomarker ions., Results: Clear separation between model and each drug group was achieved. High dose group of xiaoyaosan was much closer to control group than middle dose group and amitriptyline group. The time-dependent recovery tendency in high dose group was obtained., Conclusions: In term of anti-depression effect, high dose xiaoyaosan was the most effective and amitriptyline equaled middle dose xiaoyaosan as shown by metabolomics strategy and behavior tests. Some common and characteristic metabolites on the anti-depression of xiaoyaosan and amitriptyline were obtained. The work showed metabolomics is a valuable tool in studying the efficacy and potential biomarkers of therapeutic effect of complex prescriptions., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)