背景:抑郁症不仅损害中枢神经系统,还包括主机的外围系统。肠道菌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,大大缓解焦虑,认知障碍,尤其是胃肠功能紊乱.然而,它仍然只是划伤XYS的抗抑郁机制的表面。
目的:本研究旨在从“微生物群-肠-脑”轴的角度阐明XYS的作用机制。
方法:我们首先评估了XYS对慢性不可预知轻度应激(CUMS)引起的抑郁大鼠宏观行为的影响。其次,利用菌群失调模型揭示了XYS对抑郁大鼠肠道稳态的影响。随后,通过16SrRNA基因测序技术和分子生物学方法证明了其潜在机制。最后,从“微生物群-肠-脑”的角度对XYS的抗抑郁作用进行了相关分析和可视化。
结果:我们的数据表明XYS改善了CUMS大鼠的抑郁样症状,部分取决于肠道微生物群的存在。此外,我们说明了XYS逆转了CUMS诱导的抑郁大鼠的肠道菌群失调,降低了拟杆菌/Firmicutes比率和拟杆菌的丰度,和棒状杆菌,同时增加乳杆菌和阿德氏杆菌的丰度。拟杆菌的显着富集和脂多糖(LPS)的水平表明抑郁症损害了免疫反应和肠道屏障。机械上,XYS显著下调抑郁大鼠结肠和脑组织TLR4/NLRP3信号通路相关因子的表达水平。此外,XYS显着增加了claudin1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:我们的研究通过“微生物群-TLR4/NLRP3信号通路-屏障”的镜头,为XYS的抗抑郁作用提供了见解,为提高临床效率和丰富药物选择提供基础,并有助于我们了解中药治疗抑郁症的机制。
BACKGROUND: 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.
OBJECTIVE: This study aims to elucidate the mechanism of actions of XYS from the perspective of \"microbiota-gut-brain\" axis.
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).
CONCLUSIONS: 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.