Arbutin ameliorated depression by inhibiting neuroinflammation and modulating intestinal flora

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-06 DOI:10.1016/j.phymed.2025.156944

Yu Cao , Kexuan Zhao , Yudi Zhao , Ying Ni , Zicheng Zhang , Xinyi Yuan , Jiamei Ning , Qinghua Song , Fan Zhao , Ling He , Tong Chen

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引用次数: 0

Abstract

Background

Arbutin (AR), a natural glycoside compound widely distributed in botanical sources, exerts neuroprotective properties. Nevertheless, the pharmacological effect of AR on depression and its underlying mechanism remain undefined.

Methods

The mice were induced by chronic unpredictable mild stress (CUMS) procedure 16S rRNA sequencing and metabolomic analyses were conducted. The in vitro neuroinflammatory model was established using lipopolysaccharide (LPS) stimulated BV2 microglia.

Results

The present study found that AR alleviated the depressive-like behaviors, inflammatory reaction, oxidative stress, restored neurotrophic factors and gut tight junction proteins. TLR4/NF-κB/IRAK1 signaling was involved in these alterations. 16S rRNA sequencing and metabolomics showed that AR enriched muribaculaceae and tryptophan metabolism. Muribaculum intestinale and AR ameliorated depressive-like behaviors, inflammation and 5-HT content, Tryptophan Hydroxylase 1 (TPH1) and Indoleamine 2,3-Dioxygenase 1 (IDO1) expressions, tryptophan metabolism and kynurenine route. The molecular docking and molecular dynamic suggested that AR might bind to TPH1 and IDO1.

Conclusion

In conclusion, AR alleviated depressive-like behavior in mice by reducing neuroinflammation, modulating gut microbiota, and TPH1/IDO1-mediated serotonin synthesis.

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熊果苷通过抑制神经炎症和调节肠道菌群改善抑郁症

darbutin （AR）是一种广泛存在于植物中的天然苷类化合物，具有神经保护作用。然而，AR对抑郁症的药理作用及其潜在机制尚不明确。方法采用慢性不可预知轻度应激法（CUMS）诱导小鼠进行16S rRNA测序和代谢组学分析。采用脂多糖（LPS）刺激BV2小胶质细胞建立体外神经炎症模型。结果本研究发现，AR可减轻抑郁样行为、炎症反应、氧化应激，恢复神经营养因子和肠道紧密连接蛋白。TLR4/NF-κB/IRAK1信号通路参与了这些改变。16S rRNA测序和代谢组学分析表明，AR丰富了鼠齿科植物和色氨酸的代谢。肠菌和AR改善了抑郁样行为、炎症和5-HT含量、色氨酸羟化酶1 （TPH1）和吲哚胺2,3-双加氧酶1 （IDO1）表达、色氨酸代谢和犬尿氨酸途径。分子对接和分子动力学表明AR可能与TPH1和IDO1结合。结论AR通过减少神经炎症、调节肠道菌群和TPH1/ ido1介导的血清素合成来减轻小鼠抑郁样行为。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.