Chang Xing, Jia Hongmei, Zhou Chao, Zhang Hongwu, Yu Meng, Yang Junshan, Zou Zhongmei
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Dec 1;1006:16-29. doi: 10.1016/j.jchromb.2015.10.007. Epub 2015 Oct 20.
Chaihu-Shu-Gan-San (CSGS) is a classical traditional Chinese medicine formula for the treatment of depression. As one of the single herbs in CSGS, Bai-Shao displayed antidepressant effect. In order to explore the role of Bai-Shao towards the antidepressant effect of CSGS, the metabolic regulation and chemical profiles of CSGS with and without Bai-Shao (QBS) were investigated using metabonomics integrated with chemical fingerprinting. At first, partial least squares regression (PLSR) analysis was applied to characterize the potential biomarkers associated with chronic unpredictable mild stress (CUMS)-induced depression. Among 46 differential metabolites found in the ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) and (1)H NMR-based urinary metabonomics, 20 were significantly correlated with the preferred sucrose consumption observed in behavior experiments and were considered as biomarkers to evaluate the antidepressant effect of CSGS. Based on differential regulation on CUMS-induced metabolic disturbances with CSGS and QBS treatments, we concluded that Bai-Shao made crucial contribution to CSGS in the improvement of the metabolic deviations of six biomarkers (i.e., glutamate, acetoacetic acid, creatinine, xanthurenic acid, kynurenic acid, and N-acetylserotonin) disturbed in CUMS-induced depression. While the chemical constituents of Bai-Shao contributed to CSGS were paeoniflorin, albiflorin, isomaltopaeoniflorin, and benzoylpaeoniflorin based on the multivariate analysis of the UPLC-Q-TOF/MS chemical profiles from CSGS and QBS extracts. These findings suggested that Bai-Shao played an indispensable role in the antidepressant effect of CSGS.
柴胡疏肝散（CSGS）是一种治疗抑郁症的经典中药方剂。作为CSGS中的单味药之一，白芍具有抗抑郁作用。为了探究白芍对CSGS抗抑郁作用的影响，采用代谢组学结合化学指纹图谱技术，对含白芍（QBS）和不含白芍的CSGS的代谢调控及化学特征进行了研究。首先，应用偏最小二乘回归（PLSR）分析来表征与慢性不可预测轻度应激（CUMS）诱导的抑郁症相关的潜在生物标志物。在超高效液相色谱四极杆飞行时间质谱（UPLC-Q-TOF/MS）和基于1H NMR的尿液代谢组学中发现的46种差异代谢物中，有20种与行为实验中观察到的蔗糖偏好消耗显著相关，被认为是评估CSGS抗抑郁作用的生物标志物。基于CSGS和QBS处理对CUMS诱导的代谢紊乱的差异调节，我们得出结论，白芍对CSGS改善CUMS诱导的抑郁症中六种生物标志物（即谷氨酸、乙酰乙酸、肌酐、黄尿酸、犬尿酸和N-乙酰血清素）的代谢偏差起关键作用。而基于对CSGS和QBS提取物的UPLC-Q-TOF/MS化学图谱的多变量分析，白芍对CSGS有贡献化学成分是芍药苷、 albiflorin、异麦芽糖芍药苷和苯甲酰芍药苷。这些发现表明，白芍在CSGS的抗抑郁作用中发挥了不可或缺的作用。
