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探讨葛根素抗抑郁作用的潜在机制:通过肠-脑轴的抗炎反应。

Exploring the potential antidepressant mechanisms of puerarin: Anti-inflammatory response via the gut-brain axis.

机构信息

School of Chemical and Biological Engineering, Yichun University, Yichun 336000, China.

School of Aesthetic Medicine, Yichun University, Yichun 336000, China.

出版信息

J Affect Disord. 2022 Aug 1;310:459-471. doi: 10.1016/j.jad.2022.05.044. Epub 2022 May 11.

DOI:10.1016/j.jad.2022.05.044
PMID:35568321
Abstract

BACKGROUND

Puerarin has been shown to have a good antidepressant effect, and our previous study found that it can remedy stress-induced dysbiosis. However, its gut microbiota-related mechanism has not been fully elucidated. Therefore, this study aimed to investigate the potential link between puerarin on gut microbiota and inflammatory responses in depressed rats.

METHODS

A chronic unpredictable mild stress (CUMS) rat model of depression was established, open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST) were used to evaluate its antidepressant effect. 16S rRNA sequencing was performed to identify the rat fecal microflora. At the same time, inflammatory cytokines, colonic histopathological changes, and brain-derived neurotrophic factor (BDNF), nuclear factor kappa-B (NF-κB), inhibitor a of NF-κB (IκB-α) protein expression were detected.

RESULTS

Puerarin attenuated CUMS-induced depressive-like behavior and gut microbiota dysregulation in rats, significantly reducing the abundance of harmful bacteria such as Desulfovibrio, Verrucomicrobiae, and Verrucomicrobia. In addition, puerarin can also reduce the pro-inflammatory factors and increase the level of anti-inflammatory factors in depressed rats, improve the damaged colon tissue, enhance the expression of BDNF and IκB-α in the hippocampus and inhibit the expression of NF-κB.

LIMITATIONS

Direct evidence that puerarin improves depressive-like behaviors via gut microbiota is lacking.

CONCLUSION

The underlying mechanism of puerarin's antidepressant-like effect is closely related to the bidirectional communication of the microbiota-gut-brain axis by regulating the inflammatory response.

摘要

背景

葛根素已被证明具有良好的抗抑郁作用,我们之前的研究发现它可以纠正应激引起的肠道菌群失调。然而,其与肠道菌群相关的机制尚未完全阐明。因此,本研究旨在探讨葛根素对抑郁大鼠肠道菌群和炎症反应的潜在联系。

方法

建立慢性不可预测轻度应激(CUMS)大鼠抑郁模型,采用旷场试验(OFT)、糖水偏好试验(SPT)和强迫游泳试验(FST)评估其抗抑郁作用。通过 16S rRNA 测序鉴定大鼠粪便微生物群。同时,检测炎症细胞因子、结肠组织病理学变化以及脑源性神经营养因子(BDNF)、核因子 kappa-B(NF-κB)、NF-κB 抑制剂 a(IκB-α)蛋白表达。

结果

葛根素可减轻 CUMS 诱导的大鼠抑郁样行为和肠道菌群失调,显著降低脱硫弧菌、疣微菌和疣微菌等有害菌的丰度。此外,葛根素还可以降低抑郁大鼠的促炎因子水平,增加抗炎因子水平,改善受损的结肠组织,增强海马 BDNF 和 IκB-α 的表达,抑制 NF-κB 的表达。

局限性

缺乏葛根素通过肠道菌群改善抑郁样行为的直接证据。

结论

葛根素抗抑郁样作用的潜在机制与其通过调节炎症反应,双向沟通肠道菌群-肠-脑轴密切相关。

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