温胆汤通过调节肠道菌群和色氨酸代谢对失眠有治疗作用

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-29 DOI:10.1016/j.phymed.2025.157028

Yuan Tian , Jianguo Meng , Dezhu Zhang , Bingtao Zhai , Jiangxue Cheng , Junbo Zou , Yajun Shi , Dongyan Guo

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引用次数: 0

摘要

背景：睡眠一直是威胁人类健康的公共问题。温胆汤对失眠有较好的治疗效果。然而，其改善睡眠的机制尚不清楚。目的从肠道菌群和代谢的角度探讨WDD治疗失眠的可能机制。方法采用UHPLCOrbitrap /MS对WDD进行化学成分分析。通过行为学、酶联免疫吸附、组织病理学、免疫荧光、免疫印迹等方法观察WDD对pppa致失眠大鼠的治疗效果。结合16S rRNA测序、非靶向代谢组学和网络药理学，探讨WDD治疗失眠的机制。通过抗生素治疗和粪便微生物群移植（FMT）验证了肠道微生物群在WDD治疗中的作用。使用靶向代谢组学检测FMT后粪便色氨酸代谢物的变化。此外，利用RT-qPCR和western blotting研究潜在的机制。结果swdd能有效缩短失眠大鼠的睡眠潜伏期，延长睡眠时间，减轻焦虑样行为，减轻神经元损伤，调节神经递质水平。此外，WDD减轻了肠道损伤，减少了Iba-1阳性细胞的数量，增加了结肠、血清和海马中IL-10水平，降低了IL-6、IL-1β、TNF-α和LPS水平。Occludin、Claudin-1和ZO-1在结肠和脑中的表达也增加。16S rRNA测序表明，WDD改善了肠道微生物群紊乱。非靶向代谢组学和网络药理学共同提示WDD可调节色氨酸代谢。抗生素治疗和FMT证实了肠道微生物群参与WDD缓解失眠的治疗效果。粪便、血清和海马色氨酸代谢物的变化证实了WDD对色氨酸代谢的调节作用。进一步的机制分析表明，WDD可能通过抑制吲哚胺2,3-双加氧酶1和犬尿氨酸-3-单加氧酶的表达来纠正色氨酸代谢异常的犬尿氨酸途径。结论wdd可通过调节肠道菌群和色氨酸代谢，调节神经递质紊乱，降低炎性细胞因子水平，强化肠屏障和血脑屏障，从而改善睡眠。本研究为WDD通过微生物-肠-脑轴对失眠的潜在治疗作用提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Wendan Decoction exerts therapeutic effects on insomnia by regulating gut microbiota and tryptophan metabolism

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Wendan Decoction exerts therapeutic effects on insomnia by regulating gut microbiota and tryptophan metabolism

Background

Insomnia has been a public problem threatening human health. Wendan Decoction (WDD) has good therapeutic effects on insomnia. However, its mechanism to improve sleep remains unclear.

Purpose

To investigate the potential mechanism of WDD in treating insomnia from the perspective of gut microbiota and metabolism.

Methods

The chemical composition of WDD was analyzed by UHPLCOrbitrap Exploris/MS. The efficacy of WDD on PCPA-induced insomnia rats was evaluated through behavioral tests, ELISA, histopathological examination, immunofluorescence and western blotting. 16S rRNA sequencing, untargeted metabolomics, and network pharmacology were integrated to explore the mechanism of WDD in treating insomnia. The role of gut microbiota in WDD treatment was validated by antibiotic treatment and fecal microbiota transplantation (FMT). Targeted metabolomics was used to detect changes in fecal tryptophan metabolites after FMT. Additionally, RT-qPCR and western blotting were used to investigate the potential mechanisms.

Results

WDD effectively shortened sleep latency, prolonged sleep duration, alleviated anxiety-like behaviors, attenuated neuronal damage, and modulated neurotransmitter levels in rats with insomnia. Moreover, WDD alleviated intestinal damage, reduced the number of Iba-1 positive cells, increased IL-10 levels and decreased IL-6, IL-1β, TNF-α and LPS levels in the colon, serum and hippocampus. It also increased the expression of Occludin, Claudin-1, and ZO-1 in both the colon and brain. 16S rRNA sequencing suggested that WDD improved gut microbiota disorders. Untargeted metabolomics and network pharmacology jointly suggested that WDD could regulate tryptophan metabolism. Antibiotic treatment and FMT confirmed the involvement of gut microbiota in the therapeutic effects of WDD in alleviating insomnia. Changes of tryptophan metabolites in feces, serum, and hippocampus confirmed the regulatory effect of WDD on tryptophan metabolism. Further mechanistic analysis suggested that WDD may correct the abnormal kynurenine pathway of tryptophan metabolism through inhibition of the expression of indoleamine 2,3-dioxygenase 1 and kynurenine-3-monooxygenase.

Conclusion

WDD can modulate the neurotransmitter disorders, reduce inflammatory cytokine levels, and strengthen the intestinal barrier and blood-brain barrier by regulating gut microbiota and tryptophan metabolism, thereby improving sleep. This study provides evidence for the potential therapeutic effect of WDD on insomnia via the microbiota-gut-brain axis.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.