Du Hongli, Zhao Hongxia, Lai Xueli, Lin Qishan, Zhu Zhenyu, Chai Yifeng, Lou Ziyang
School of Pharmacy, Second Military Medical University, Shanghai, China.
Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Biomed Chromatogr. 2017 Jul;31(7). doi: 10.1002/bmc.3923. Epub 2017 Jan 24.
Depression is a major cause of illness and disability. We applied untargeted metabolomics using mass spectrometry to identify metabolic signatures associated with depression in serum and explored the antidepressant effects of lilies and Rhizoma Anemarrhenae on an experimental model of chronic unpredictable mild stress (CUMS). Meanwhile metabolomics based on UHPLC-Q-TOF-MS was used to study the change in metabolites in CUMS rat serum and to evaluate the effects of Rhizoma Anemarrhenae and lilies (alone and in combination). Partial least squares-discriminant analysis identified 30 metabolites as decisive marker compounds that discriminated the CUMS rats and the control rats. The majority of these metabolites were involved in amino acid metabolism, the tricarboxylic acid cycle, and phosphoglyceride metabolism. The reliability of the metabolites was evaluated by the administration of lilies, Rhizoma Anemarrhenae, fluoxetine and the combination of lilies and Rhizoma Anemarrhenae to the CUMS rats. Behavior studies demonstrated that treatment with the combination of lilies and Rhizoma Anemarrhenae resulted in optimal antidepressant effects. The combination treatment was almost as effective as fluoxetine. Our results suggest that lilies and Rhizoma Anemarrhenae demonstrate synergistically antidepressant effects in CUMS via the regulation of multiple metabolic pathways. These findings provide insight into the pathophysiological mechanisms underlying CUMS and suggest innovative and effective treatments for this disorder.
抑郁症是导致疾病和残疾的主要原因。我们运用质谱非靶向代谢组学技术来识别血清中与抑郁症相关的代谢特征，并探究百合和知母对慢性不可预测轻度应激（CUMS）实验模型的抗抑郁作用。同时，基于超高效液相色谱-四极杆飞行时间质谱联用仪（UHPLC-Q-TOF-MS）的代谢组学用于研究CUMS大鼠血清中代谢物的变化，并评估知母和百合（单独及联合使用）的效果。偏最小二乘判别分析确定了30种代谢物作为区分CUMS大鼠和对照大鼠的决定性标志物化合物。这些代谢物大多参与氨基酸代谢、三羧酸循环和磷酸甘油酯代谢。通过给CUMS大鼠施用百合、知母、氟西汀以及百合与知母的组合来评估代谢物的可靠性。行为学研究表明，百合与知母联合治疗产生了最佳抗抑郁效果。联合治疗几乎与氟西汀一样有效。我们的研究结果表明，百合和知母通过调节多种代谢途径在CUMS中显示出协同抗抑郁作用。这些发现为CUMS潜在的病理生理机制提供了见解，并为该疾病提出了创新有效的治疗方法。
