Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China.
Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China.
J Ethnopharmacol. 2024 Dec 5;335:118683. doi: 10.1016/j.jep.2024.118683. Epub 2024 Aug 8.
ETHNOPHARMACOLOGICAL RELEVANCE: Depression impairs not only central nervous system, but also peripheral systems of the host. Gut microbiota have been proved to be involved in the pathogenesis of depression. Xiaoyaosan (XYS) has a history of over a thousand years in China for treating depression, dramatically alleviating anxiety, cognitive disorders, and especially gastrointestinal dysfunctions. Yet, it still just scratches the surface of the anti-depression mechanisms of XYS. AIM OF THE STUDY: This study aims to elucidate the mechanism of actions of XYS from the perspective of "microbiota-gut-brain" axis. MATERIALS AND METHODS: We firstly evaluated the effects of XYS on the macroscopic behaviors of depressed rats that induced by chronic unpredictable mild stress (CUMS). Secondly, the effects of XYS on intestinal homeostasis of depressed rats were revealed by using dysbacteriosis model. Subsequently, the underlying mechanisms were demonstrated by 16S rRNA gene sequencing technology and molecular biology methods. Finally, correlation analysis and visualization of the anti-depression effects of XYS were performed from the "microbiota - gut - brain" perspective. RESULTS: Our data indicated that XYS ameliorated the depression-like symptoms of CUMS rats, partly depending on the presence of gut microbiota. Furthermore, we illustrated that XYS reversed CUMS-induced gut dysbiosis of depressed rats in terms of decreasing the Bacteroidetes/Firmicutes ratio and the abundances of Bacteroides, and Corynebacterium, while increasing the abundances of Lactobacillus and Adlercreutzia. The significant enrichment of Bacteroides and the level of lipopolysaccharides (LPS) suggested that depression damaged the immune responses and gut barrier. Mechanistically, XYS significantly down-regulated the expression levels of factors that involved in TLR4/NLRP3 signaling pathway in the colon and brain tissues of depressed rats. In addition, XYS significantly increased the levels of claudin 1 and ZO-1, showing that XYS positively maintained the integrity of gut and blood-brain barriers (BBB). CONCLUSION: Our study offers insights into the anti-depression effects of XYS through a lens of "microbiota-TLR4/NLRP3 signaling pathway-barriers", providing a foundation for enhancing clinical efficiency and enriching drug selection, and contributing to our understanding of the mechanisms of traditional Chinese medicines (TCMs) in treating depression.
民族药理学相关性：抑郁症不仅会损害中枢神经系统，还会损害宿主的外周系统。肠道微生物群已被证明与抑郁症的发病机制有关。逍遥散（XYS）在中国已有一千多年的历史，用于治疗抑郁症，可显著缓解焦虑、认知障碍，特别是胃肠道功能障碍。然而，它仍然只是触及了 XYS 抗抑郁机制的表面。
研究目的：本研究旨在从“微生物群-肠道-大脑”轴的角度阐明 XYS 的作用机制。
材料和方法：我们首先评估了 XYS 对慢性不可预测轻度应激（CUMS）诱导的抑郁大鼠宏观行为的影响。其次，通过菌群失调模型揭示了 XYS 对抑郁大鼠肠道内稳态的影响。随后，通过 16S rRNA 基因测序技术和分子生物学方法证明了潜在机制。最后，从“微生物群-肠道-大脑”的角度对 XYS 的抗抑郁作用进行了相关性分析和可视化。
结果：我们的数据表明，XYS 改善了 CUMS 大鼠的抑郁样症状，部分依赖于肠道微生物群的存在。此外，我们表明 XYS 可以逆转 CUMS 诱导的抑郁大鼠肠道菌群失调，降低拟杆菌门/厚壁菌门的比值以及拟杆菌和棒状杆菌的丰度，同时增加乳杆菌和 Adlercreutzia 的丰度。Bacteroides 的显著富集和脂多糖（LPS）水平表明，抑郁破坏了免疫反应和肠道屏障。从机制上讲，XYS 显著下调了 TLR4/NLRP3 信号通路相关因子在抑郁大鼠结肠和脑组织中的表达水平。此外，XYS 显著增加了 Claudin 1 和 ZO-1 的水平，表明 XYS 积极维持了肠道和血脑屏障（BBB）的完整性。
结论：本研究通过“微生物群-TLR4/NLRP3 信号通路-屏障”的视角，提供了对 XYS 抗抑郁作用的深入了解，为提高临床疗效和丰富药物选择提供了依据，并有助于我们理解中药（TCM）治疗抑郁症的机制。
MedComm (2020). 2024-11-20
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