title: Dynamic analysis of the endogenous metabolites in depressed patients treated with TCM formula Xiaoyaosan using urinary (1)H NMR-based metabolomics.
abstract: BACKGROUND
  Xiaoyaosan (XYS), one of the best-known traditional Chinese medicine prescriptions with a long history of use, is composed of Bupleurum chinense DC., Paeonia lactiflora Pall., Poria cocos (Schw.) Wolf, Angelica sinensis (Oliv.) Diels, Zingiber officinale Rosc., Atractylodes macrocephala Koidz., Glycyrrhiza uralensis Fisch., and Mentha haplocalyx Briq. For centuries, XYS has been widely used in China for the treatment of mental disorders such as depression. However, the complicated mechanism underlying the antidepressant activity of XYS is not yet well-understood. This understanding is complicated by the sophisticated pathophysiology of depression and by the complexity of XYS, which has multiple constituents acting on different metabolic pathways. The variations of endogenous metabolites in depressed patients after administration of XYS may help elucidate the anti-depressant effect and mechanism of action of XYS. The aim of this study is to establish the metabolic profile of depressive disorder and to investigate the changes of endogenous metabolites in the depressed patients before and after the treatment of Xiaoyaosan using the dynamic analysis of urine metabolomics profiles based on (1)H NMR.
  
  
  METHODS
  Twenty-one depressed patients were recruited from the Traditional Chinese Medicine Department of the First Affiliated Hospital of Shanxi Medical University. Small endogenous metabolites present in urine samples were measured by nuclear magnetic resonance (NMR) and analyzed by multivariate statistical methods. The patients then received XYS treatment for six weeks, after which their Hamilton Depression Scale (HAMD) scores were significantly decreased compared with their baseline scores (p≤0.01). Eight components in urine specimens were identified that enabled discrimination between the pre- and post-XYS-treated samples.
  
  
  RESULTS
  Urinary of creatinine, taurine, 2-oxoglutarate and xanthurenic acid increased significantly after XYS treatment (p≤0.05), while the urinary levels of citrate, lactate, alanine and dimethylamine decreased significantly (p≤0.05) compared with pre-treatment urine samples. These statistically significant perturbations are involved in energy metabolism, gut microbes, tryptophan metabolism and taurine metabolism.
  
  
  CONCLUSIONS
  The symptoms of depression had been improved after 6 weeks׳ treatment of XYS according to evaluation of HAMD scores. The dynamic tendency of the 8 metabolites that changed significantly during the treatment of XYS is consistent with the improvement in symptoms of depression. These metabolites may be used as biomarkers for the diagnosis of depressive disorders or the evaluation of the antidepressant as well as the exploration of the mechanism of depression.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Jun-sheng
authors.initials: JS
authors.lastname: Tian
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China; College of Chemistry and Chemical Engineering of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Guo-jiang
authors.initials: GJ
authors.lastname: Peng
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Gao
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Yu-zhi
authors.initials: YZ
authors.lastname: Zhou
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xing
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China. Electronic address: qinxm@sxu.edu.cn.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Qin
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China; Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China. Electronic address: dugh@imm.ac.cn.
authors.forename: Guan-hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000378:metabolism / Q000627:therapeutic use*; D002681:China; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008516:Medicine, Chinese Traditional; D055432:Metabolomics; D008875:Middle Aged; D015999:Multivariate Analysis; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; C532268:xiaoyaosan
keywords: Alanine (PubChem CID: 5950); Citrate (PubChem CID: 31348); Depressed patients; Dimethylamine (PubChem CID: 674); Dynamic analysis; Glutamine (PubChem CID: 5961); Glycine (PubChem CID: 750) (PubChem CID: 31348); Lactate (PubChem CID: 5460161); Metabolomics; Nuclear magnetic resonance; Taurine (PubChem CID: 1123); Timethylamine (PubChem CID: 1146); Trimethylamine N-oxide (PubChem CID: 1145); Xanthurenic acid (PubChem CID: 5699); Xiaoyaosan