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

• Published in: Journal of pharmaceutical and biomedical analysis 2011-06, Vol.55 (3), p.533-539
• Main Authors: Su, Zhi-Heng, Li, Shu-Qi, Zou, Guo-An, Yu, Chang-Yuan, Sun, Yan-Guo, Zhang, Hong-Wu, Gu, Ying, Zou, Zhong-Mei
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; animal models; Animals; Anti-depressive effect; Antidepressive Agents - therapeutic use; biochemical pathways; Biological and medical sciences; biomarkers; Biomarkers - urine; bone resorption; Chaihu-Shu-Gan-San; Chromatography, High Pressure Liquid - instrumentation; Chromatography, High Pressure Liquid - methods; Chronic Disease; Chronic variable stress model; Depression - drug therapy; Depression - etiology; Depression - urine; Disease Models, Animal; energy metabolism; Fundamental and applied biological sciences. Psychology; General pharmacology; liver; Male; mass spectrometry; Mass Spectrometry - instrumentation; Mass Spectrometry - methods; Medical sciences; metabolites; metabolomics; Metabolomics - methods; Oriental traditional medicine; pantothenic acid; pathogenesis; pathophysiology; Pharmacology. Drug treatments; Plant Extracts - therapeutic use; proline; Rats; Rats, Wistar; Stress, Psychological - complications; Stress, Psychological - urine; therapeutics; Traditional Chinese medicines; tryptophan; Ultra performance liquid chromatography–time-of-flight mass spectrometry; ultra-performance liquid chromatography; Urinary metabonomics; urine; xanthurenic acid
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2011.02.013

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.