核桃衍生肽WSPSGR通过IDO1抑制和肠道微生物-色氨酸轴调节减轻小鼠抑郁样行为

IF 6.2 1区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of Agricultural and Food Chemistry Pub Date : 2025-10-11 DOI:10.1021/acs.jafc.5c09940

Xiao Xiao, Aijin Ma, Zhou Chen, Siting Li, Junxia Xia, Shenghua Ding, Yingmin Jia

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引用次数: 0

摘要

抑郁症是一种复杂的精神疾病，其全球影响越来越大。本研究探讨了核桃衍生肽Trp-Ser-Pro-Ser-Gly-Arg （WSPSGR）的抗抑郁机制，该肽具有吲哚胺2,3-双加氧酶1 （IDO1）抑制活性。在慢性不可预测的轻度应激（CUMS）诱导的小鼠模型中，WSPSGR通过恢复色氨酸（Trp）代谢平衡和重塑肠道微生物群组成来改善抑郁样行为。值得注意的是，它降低了ido1介导的犬尿氨酸（Kyn）途径的激活，纠正了肠道生态失调，包括降低厚壁菌门/拟杆菌门比例。这些影响共同重建了微生物-肠道-脑轴的稳态。这些发现确定IDO1是WSPSGR的关键靶点，并提示基于肽的色氨酸代谢和肠道微生物群调节可能是一种有希望的抑郁症治疗策略。

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A Walnut-Derived Peptide WSPSGR Alleviates Depressive-Like Behaviors in Mice via IDO1 Inhibition and Gut Microbiota–Tryptophan Axis Modulation

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A Walnut-Derived Peptide WSPSGR Alleviates Depressive-Like Behaviors in Mice via IDO1 Inhibition and Gut Microbiota–Tryptophan Axis Modulation

Depression is a complex psychiatric disorder with increasing global impact. This study explored the antidepressant mechanisms of Trp-Ser-Pro-Ser-Gly-Arg (WSPSGR), a walnut-derived peptide with indoleamine 2,3-dioxygenase 1 (IDO1) inhibitory activity. In a chronic unpredictable mild stress (CUMS)-induced mouse model, WSPSGR ameliorated depressive-like behaviors by restoring tryptophan (Trp) metabolic balance and reshaping gut microbiota composition. Notably, it reduced IDO1-mediated kynurenine (Kyn) pathway activation and corrected gut dysbiosis, including a decreased Firmicutes/Bacteroidota ratio. These effects collectively re-established microbiota–gut–brain axis homeostasis. These findings identify IDO1 as a key target of WSPSGR and suggest that peptide-based modulation of Trp metabolism and gut microbiota may be a promising strategy for depression therapy.

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来源期刊

Journal of Agricultural and Food Chemistry 农林科学-农业综合

CiteScore

9.90

自引率

8.20%

发文量

1375

审稿时长

2.3 months

期刊介绍： The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.