Isorhamnetin Alleviates Inflammation-Induced Crosstalk between Kynurenine Pathway and Gut Microbiota in Depressed Mice.

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI:10.4062/biomolther.2024.061
Mengjie Xu, Wei He, Ke Yan, Xinru Gao, Jun Li, Dongyue Xu, Jiao Xiao, Tingxu Yan
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引用次数: 0

Abstract

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

异鼠李素减轻抑郁症小鼠犬尿氨酸途径与肠道微生物群之间炎症诱导的串扰。
抑郁症是一种广泛存在的精神疾病,发病机制复杂,治疗效果不理想。异鼠李素是一种天然黄酮类化合物,具有抗氧化和调节免疫等神经保护作用。然而,目前还没有发现ISO抗抑郁作用的报道。本研究利用行为学、生物化学、体内外分子及生物信息学等方法,阐明异丙醇抗抑郁作用的机制基础。通过SPT和FST观察ISO对抑郁症小鼠的作用,H&E染色观察其病变。通过检测试剂盒检测犬尿氨酸通路炎症因子和指标,16sRNA检测菌群。通过分子对接研究探讨了ISO的作用靶点。此外,Western blot检测PI3K/AKT信号通路的激活情况。结果表明,ISO能增强小鼠在SPT中的糖水偏好,缩短小鼠在FST中的静止时间。此外,ISO还能抑制外周和中枢炎症,调节犬尿氨酸通路和肠道菌群的变化,抑制PI3K/AKT通路的激活,并在PI3K/AKT信号通路上与靶蛋白表现出良好的结合模式。综上所述,这些发现表明,ISO通过调节PI3K/AKT/NF-κB通路,使炎症诱导的KP与肠道微生物群紊乱之间的串扰失调正常化,从而减轻了抑郁样行为。
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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
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