Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula, has been effectively used for the treatment of depression in clinic. However, studies of its anti-depressive mechanism are challenging, accounted for the complex pathophysiology of depression, and complexity of CSGS with multiple constituents acting on different metabolic pathways. The variations of endogenous metabolites in rat model of depression after administration of CSGS may offer deeper insights into the anti-depressive effect and mechanism of CSGS. In this study, metabonomics based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of urine obtained from chronic variable stress (CVS)-induced depression model in rats with and without CSGS treatment. Through partial least squares-discriminate analysis, it was observed that metabolic perturbations induced by chronic variable stress were restored in a time-dependent pattern after treatment with CSGS. Metabolites with significant changes induced by CVS, including 3-O-methyldopa (1), pantothenic acid (2), kynurenic acid (3), xanthurenic acid (4), 2,8-dihydroxyquinoline glucuronide (5), 5-hydroxy-6-methoxyindole glucurnoide (8), L-phenylalanyl-L-hydroxyproline (9), indole-3-carboxylic acid (10), proline (11), and the unidentified metabolites (6, 2.11 min_m/z 217.0940; 7, 2.11 min_m/z 144.0799), were characterized as potential biomarkers involved in the pathogenesis of depression. The derivations of all those biomarkers can be regulated by CSGS treatment except indole-3-carboxylic acid (10), which suggested that the therapeutic effect of CSGS on depression may involve in regulating the dysfunctions of energy metabolism, tryptophan metabolism, bone loss and liver detoxification. This study indicated that the rapid and noninvasive urinary metabonomics approach may be a powerful tool to study the efficacy and mechanism of complex TCM prescriptions.
Chinese Acad Med Sci, Inst Med Plant Dev, Beijing 100193, Peoples R China;Peking Union Med Coll, Beijing 100193, Peoples R China;Beijing Univ Chem Technol, Beijing 100029, Peoples R China;Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Urumqi 830011, Peoples R China;Waters Co Ltd Shanghai, Shanghai 201203, Peoples R China
Su Zhi-Heng,Li Shu-Qi,Zou Guo-An,et al. Urinary metabonomics study of anti-depressive effect of Chaihu-Shu-Gan-San on an experimental model of depression induced by chronic variable stress in rats[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2011,55(3):533-539.