Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, China; Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, 030006, China.
Shanxi Institute for Food and Drug Control, Taiyuan, 030001, China.
J Ethnopharmacol. 2021 Aug 10;276:114167. doi: 10.1016/j.jep.2021.114167. Epub 2021 May 10.
Xiaoyaosan (XYS), a representative and classic prescription in traditional Chinese medicines (TCMs), has been used for thousands of years for treating depression. The anti-depression effect of XYS has been demonstrated both clinically and experimentally. However, it is still unclear that whether XYS could regulate the abnormalities of gut microbiota and metabolites of cecum induced by depression, and in which way. This study aimed to explore the underlying mechanism of the anti-depressant effects of XYS from the perspective of cecal microbiota and metabolites.
Chronic unpredictable mild stress (CUMS)-induced depression-like rats were used as the depression animal model. Various classic behavioral tests were performed to assess the anti-depressant effects of XYS. Additionally, the composition, the richness, and the diversity of the cecum microbiota were assessed by 16S rRNA gene sequencing technology. Besides, the metabolic profiling of cecum samples was analyzed by H-NMR metabolomics. Multivariate data analysis was then applied to screen the differential metabolites and to characterize the changes in cecum metabolites. Moreover, a correlation analysis between differential metabolites and crucial microbiota was conducted.
XYS significantly improved depressive behaviors and the abnormal diversity of cecum microbiota induced by CUMS. At the phylum level, XYS could significantly increase the abundance of Firmicutes while decrease the abundance of Actinobacteria in depressed rats. XYS significantly regulated the abundances of 9 out of 13 potential microbial biomarkers at the genus level. Cecal metabolomics showed that XYS could also regulate the abnormal levels of alanine, proline, lactate, and valine of depression rats.
This study revealed, for the first time, from the perspectives of microbiota and cecum metabolites, the anti-depression mechanisms of XYS. This study is of significance for not only comprehensively understanding the anti-depression effects and mechanisms of XYS, but also for providing a research approach for revealing the underlying mechanisms of action of TCMs, i.e. to apply a combination of 16S rRNA gene sequencing and metabolomics.
逍遥散（XYS）是中药（TCM）的代表性经典方剂之一，已有数千年的历史用于治疗抑郁症。XYS 的抗抑郁作用已在临床和实验中得到证实。然而，目前尚不清楚 XYS 是否可以调节抑郁症引起的盲肠微生物群和代谢物的异常，以及以何种方式调节。本研究旨在从盲肠微生物群和代谢物的角度探讨 XYS 的抗抑郁作用的潜在机制。
采用慢性不可预测轻度应激（CUMS）诱导的抑郁样大鼠作为抑郁动物模型。进行了各种经典行为测试，以评估 XYS 的抗抑郁作用。此外，通过 16S rRNA 基因测序技术评估盲肠微生物群的组成、丰富度和多样性。此外，通过 H-NMR 代谢组学分析盲肠样本的代谢谱。然后应用多元数据分析筛选差异代谢物并描述盲肠代谢物的变化。此外，还进行了差异代谢物与关键微生物之间的相关性分析。
XYS 显著改善了 CUMS 诱导的抑郁行为和盲肠微生物群的异常多样性。在门水平上，XYS 可显著增加抑郁大鼠中厚壁菌门的丰度，同时降低放线菌门的丰度。XYS 可显著调节 13 个潜在微生物生物标志物中的 9 个属水平的丰度。盲肠代谢组学显示，XYS 还可以调节抑郁大鼠丙氨酸、脯氨酸、乳酸和缬氨酸的异常水平。
本研究首次从微生物群和盲肠代谢物的角度揭示了 XYS 的抗抑郁机制。本研究不仅对全面了解 XYS 的抗抑郁作用和机制具有重要意义，而且为揭示 TCM 作用的潜在机制提供了一种研究方法，即应用 16S rRNA 基因测序和代谢组学相结合的方法。
