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
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
复制标题
DOI：
10.1016/j.jpba.2011.02.013
复制
发表时间：
2011-06-01
影响因子：
3.4
通讯作者：
Zou, Zhong-Mei
中科院分区：
文献类型：
--
作者：
Su, Zhi-Heng;Li, Shu-Qi;Zou, Zhong-Mei
柴胡疏肝散是一种治疗抑郁症的中药方剂，临床上用于治疗抑郁症疗效显著。然而，其抗抑郁机制的研究是具有挑战性的，占抑郁症的复杂的病理生理学，和复杂的CSGS与多种成分作用于不同的代谢途径。研究CSGS对抑郁症模型大鼠内源性代谢产物的影响，为CSGS的抗抑郁作用及其机制提供了新的思路。本研究采用超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-QTOF-MS）对慢性可变应激（CVS）抑郁模型大鼠尿液代谢指纹图谱进行分析。通过偏最小二乘判别分析，观察到慢性可变应激引起的代谢紊乱在CSGS处理后以时间依赖的模式恢复。CVS引起显著变化的代谢产物，包括3-O-甲基多巴（1）、泛酸（2）、犬尿烯酸（3）、黄尿酸（4）、2，8-二羟基喹啉葡萄糖醛酸苷（5）、5-羟基-6-甲氧基吲哚葡萄糖醛酸苷（8）、L-苯丙氨酰-L-羟脯氨酸（9）、吲哚-3-羧酸（10）、脯氨酸（11）和未鉴定代谢产物（6，2.11 min_m/z 217.0940; 7，2.11 min_m/z 144.0799）被表征为参与抑郁症发病机制的潜在生物标志物。除吲哚-3-羧酸（indole-3-carboxylic acid）外，所有这些生物标志物的衍生都可以通过CSGS治疗来调节（10），这表明CSGS对抑郁症的治疗作用可能涉及调节能量代谢、色氨酸代谢、骨丢失和肝脏解毒功能障碍。本研究表明，快速、无创的尿液代谢组学方法有望成为研究中药复方药效及其作用机制的有力工具。(C)2011 Elsevier B. V.保留所有权利。
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. (C) 2011 Elsevier B.V. All rights reserved.