Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, China; Key Laboratory of Effective Substances Research and Utilization in Traditional Chinese Medicine of Shanxi Province, Shanxi University, Taiyuan, 030006, China.
Shanxi Institute for Food and Drug Control, Taiyuan, 030001, China.
J Ethnopharmacol. 2020 May 23;254:112726. doi: 10.1016/j.jep.2020.112726. Epub 2020 Mar 2.
Xiaoyaosan (XYS), a represent and classic TCM prescription, consists of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae. XYS can sooth the liver and strengthen the spleen through improving the circulation of qi and nourishing blood according to the TCM theory, therefore exhibiting anti-depression effects.
This study was conducted to investigate the compatibility rule of antidepressant effect of XYS by using both the "Efficacy Compositions" research strategy and fecal metabolomics approach.
XYS was divided into two efficacy groups, i.e. the Shugan (SG) and the Jianpi (JP) groups, according to the efficacies of both XYS and the eight herbs recorded in the TCM theory and the research strategy of "Efficacy Compositions". A CUMS-induced depression model was constructed, where rats were randomly divided into 5 groups: negative control (NC), CUMS model (MS), XYS, SG, and JP. Multivariate data analysis including Principal Components Analysis (PCA) and Orthogonal Partial Least Squares-Discriminate Analysis (OPLS-DA) was utilized. Efficacy Index (EI) was calculated.
Metabolic profiling by PCA showed that XYS exhibited the strongest effect than the two efficacy groups, locating closest to the control group. OPLS-DA showed 10 metabolites were identified as potential biomarkers for the CUMS-induced depression. 8 potential biomarkers were significantly reversed by XYS while 5 and 4 biomarkers were reversed by SG and JP, respectively. The results of regulatory degrees showed that XYS had the highest EI than SG and JP. Concerning metabolic pathways, XYS regulated all the seven metabolic pathways associated with CUMS-induced depression, while SG and JP groups regulated six and three pathways, respectively.
The antidepressant effect of XYS was stronger than that of SG and JP. The combined effects of SG and JP brought the integrated antidepressant effect of XYS. This study suggests that a combination of "Efficacy Compositions" strategy and metabolomics approach has great potentials in comprehensively and deeply understanding the scientific connotation of the compatibility rule of TCM prescriptions.
逍遥散（XYS）是一种代表和经典的中药方剂，由柴胡、当归、白芍、白术、茯苓、薄荷、生姜和甘草组成。根据中医理论，XYS 通过改善气血循环来疏肝健脾，从而表现出抗抑郁作用。
本研究采用“功效成分”研究策略和粪便代谢组学方法，探讨 XYS 抗抑郁作用的配伍规律。
根据中医理论和“功效成分”研究策略，将 XYS 分为疏肝（SG）和健脾（JP）两个功效组。构建 CUMS 诱导的抑郁模型，将大鼠随机分为 5 组：阴性对照组（NC）、CUMS 模型组（MS）、XYS 组、SG 组和 JP 组。采用主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）等多元数据分析方法。计算功效指数（EI）。
PCA 的代谢谱分析表明，XYS 的作用最强，与对照组最接近。OPLS-DA 显示 10 种代谢物被鉴定为 CUMS 诱导的抑郁潜在生物标志物。XYS 可显著逆转 8 种潜在生物标志物，SG 和 JP 可分别逆转 5 种和 4 种生物标志物。调节程度的结果表明，XYS 的 EI 高于 SG 和 JP。关于代谢途径，XYS 调节了与 CUMS 诱导的抑郁相关的所有 7 条代谢途径，而 SG 和 JP 组分别调节了 6 条和 3 条代谢途径。
XYS 的抗抑郁作用强于 SG 和 JP。SG 和 JP 的联合作用带来了 XYS 的综合抗抑郁作用。本研究表明，“功效成分”策略与代谢组学方法的结合具有全面深入理解中药方剂配伍规律的巨大潜力。
