Synergistic stress-relieving and cognitive-enhancing effects of walnut peptide and theanine in human brain organoid and mouse stress models

作者：Qixing Zhong, Qinxi Li, Xiuzhen Jia, Liang Hu, Yingqian Zhang, J. Zu, Yao He, Xiaojie Li, Yu Wang, Haotian Feng, Jingyu Hao, Zifu Zhao, Jian He, Zhihui Zhong · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.157187 · 被引用次数：6 · 研究领域：Regulation of Appetite and Obesity、Nuts composition and effects、Sirtuins and Resveratrol in Medicine

BACKGROUND: Stress is a prevalent mental health concern that often emerges in late adolescence or early adulthood. Since 2007, the Food and Drug Administration (FDA) has not approved any novel anxiolytic pharmaceuticals, leading to increased interest in nutritional supplements as alternative therapies for stress management. PURPOSE: Building on our previous study, this work aims to investigate the synergistic effects of Theanine (Th) and Walnut Peptide (WP) on stress mitigation and cognitive enhancement. STUDY DESIGN: This study employed both in vitro and in vivo approaches. The former employed the human brain organoid stress (BO-stress) model, while the latter utilized the C57BL/6J mouse-stress model to evaluate the effect of Th and WP. METHODS: In the BO-stress model, the Th and WP combination was assessed for its effects on stress levels and the expression of neurotransmitters (GABA: Gamma-Aminobutyric Acid; 5-HT: serotonin; DA: dopamine; Ach: acetylcholine), as well as brain-derived neurotrophic factor (BDNF) and serotonin transporter (SERT). In the in vivo study, mice were administered Th (85 mg/ml) + WP (200 mg/ml) or with vehicles (e.g., powder, yogurt, milk), and assessed for stress and cognitive performance. Neurotransmitter levels, SERT and BDNF expression levels were also measured. RESULTS: The BO-stress model demonstrated that Th + WP reduced stress and regulated the expression of neurotransmitters and neurotrophic factors. In the mouse-stress model, the treatment...