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多组学揭示了柴胡低极性部位抗抑郁作用的机制。

Multi-omics reveals the mechanisms of antidepressant-like effects of the low polarity fraction of Bupleuri Radix.

机构信息

Modern Research Center for Traditional Chinese Medicine of Shanxi University, No.92, Wucheng Road, Taiyuan, 030006, PR China; College of Chemistry and Chemical Engineering, Shanxi University, No. 92, Wucheng Road, Taiyuan, 030006, PR China.

Modern Research Center for Traditional Chinese Medicine of Shanxi University, No.92, Wucheng Road, Taiyuan, 030006, PR China.

出版信息

J Ethnopharmacol. 2020 Jun 28;256:112806. doi: 10.1016/j.jep.2020.112806. Epub 2020 Mar 29.

DOI:10.1016/j.jep.2020.112806
PMID:32234596
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Radix Bupleuri (Bupleurum chinense DC.) is a traditional Chinese medicine that has the effect of soothing the liver and relieving depression, and widely used in the field of antidepression.

AIM OF THE STUDY

The low polarity fraction of Bupleuri Radix (PBR) has proved to be effective for the treatment of depression based on the results of our previous study. However, mechanisms of definite antidepressant-like effects remained unclear. The purpose of this study is to reveal mechanisms of antidepressant-like effects of PBR with multi-dimensional omics.

MATERIALS AND METHODS

LC-MS metabolomics combined with 16S rRNA gene sequencing were used to investigate the effects of PBR on gut microbiota and metabolites in CUMS-induced depression, and Pearson correlation analysis was carried out on gut microbiota and metabolites.

RESULTS

PBR significantly improved depression-like behaviors in the CUMS model rats. Moreover, PBR significantly increased the levels of BDNF in the hippocampus. Cecum contents metabolomics revealed that 16 biomarkers associated with PBR antidepressant effect were screened, which were involved 3 metabolic pathways including primary bile acid biosynthesis, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism. Gut microbiota further analysis demonstrated that PBR increased the diversity of gut microbiota, and significantly inhibited the growth of [Prevotella] and Ochrobactrum. Furthermore, Pearson analysis revealed there was a strong correlation between cecum contents of metabolites and gut microbiota.

CONCLUSIONS

PBR improved depression-like behavior by regulating metabolic profiles and gut microbiota, and contributing to further understand the entailed antidepressant-like mechanisms of PBR.

摘要

民族药理学相关性

柴胡(柴胡 DC.)是一种中药,具有疏肝解郁的功效,在抗抑郁领域广泛应用。

研究目的

基于我们之前的研究结果,证明了柴胡的低极性部位(PBR)对治疗抑郁症有效。然而,其明确的抗抑郁样作用机制仍不清楚。本研究旨在通过多维组学揭示 PBR 抗抑郁样作用的机制。

材料和方法

采用 LC-MS 代谢组学结合 16S rRNA 基因测序技术,研究 PBR 对 CUMS 诱导的抑郁大鼠肠道微生物群和代谢物的影响,并对肠道微生物群和代谢物进行 Pearson 相关性分析。

结果

PBR 显著改善了 CUMS 模型大鼠的抑郁样行为。此外,PBR 显著增加了海马体中的 BDNF 水平。盲肠内容物代谢组学揭示了与 PBR 抗抑郁作用相关的 16 个生物标志物,涉及包括初级胆汁酸生物合成、牛磺酸和次牛磺酸代谢、乙醛酸和二羧酸代谢在内的 3 个代谢途径。肠道微生物群进一步分析表明,PBR 增加了肠道微生物群的多样性,并显著抑制了[Prevotella]和 Ochrobactrum 的生长。此外,Pearson 分析表明,盲肠内容物代谢物与肠道微生物群之间存在很强的相关性。

结论

PBR 通过调节代谢谱和肠道微生物群改善了抑郁样行为,有助于进一步了解 PBR 抗抑郁样作用的相关机制。

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