Potential Mechanisms of Casein Hexapeptide YPVEPF on Stress-Induced Anxiety and Insomnia Mice and Its Molecular Effects and Key Active Structure,Journal of Agricultural and Food Chemistry

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Potential Mechanisms of Casein Hexapeptide YPVEPF on Stress-Induced Anxiety and Insomnia Mice and Its Molecular Effects and Key Active Structure
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-03-19 , DOI: 10.1021/acs.jafc.3c05718
Jingjing Qian ₁ , Lin Zheng _{1,

2,

3} , Mingtao Huang ₁ , Mouming Zhao _{1,

2,

4}

Affiliation

The hexapeptide YPVEPF with strong sleep-enhancing effects could be detected in rat brain after a single oral administration as we previously proved. In this study, the mechanism and molecular effects of YPVEPF in the targeted stress-induced anxiety mice were first investigated, and its key active structure was further explored. The results showed that YPVEPF could significantly prolong sleep duration and improve the anxiety indexes, including prolonging the time spent in the open arms and in the center. Meanwhile, YPVEPF showed strong sleep-enhancing effects by significantly increasing the level of the GABA/Glu ratio, 5-HT, and dopamine in brain and serum and regulating the anabolism of multiple targets, but the effects could be blocked by bicuculline and WAY100135. Moreover, the molecular simulation results showed that YPVEPF could stably bind to the vital GABA_A and 5-HT_1A receptors due to the vital structure of Tyr-Pro-Xaa-Xaa-Pro-, and the electrostatic and van der Waals energy played dominant roles in stabilizing the conformation. Therefore, YPVEPF displayed sleep-enhancing and anxiolytic effects by regulating the GABA-Glu metabolic pathway and serotoninergic system depending on distinctive self-folding structures with Tyr and two Pro repeats.

中文翻译：

酪蛋白六肽YPVEPF对应激性焦虑和失眠小鼠的潜在机制及其分子效应和关键活性结构

正如我们之前所证明的，单次口服后大鼠大脑中就可以检测到具有强睡眠促进作用的六肽YPVEPF。本研究首先研究了YPVEPF对应激性焦虑小鼠的作用机制和分子效应，并进一步探讨了其关键活性结构。结果显示，YPVEPF可以显着延长睡眠时间，改善焦虑指数，包括延长张开双臂和中心的时间。同时，YPVEPF通过显着提高大脑和血清中的GABA/Glu比值、5-HT和多巴胺水平并调节多个靶点的合成代谢而表现出强大的促进睡眠作用，但该作用可以被荷包牡丹碱和WAY100135阻断。此外，分子模拟结果表明，由于Tyr-Pro-Xaa-Xaa-Pro-的重要结构，YPVEPF能够稳定地与重要的GABA _A和5-HT _1A受体结合，并且静电和范德华能量起主导作用。稳定构象的作用。因此，YPVEPF 通过调节 GABA-Glu 代谢途径和血清素能系统（取决于 Tyr 和两个 Pro 重复序列的独特自折叠结构）来显示增强睡眠和抗焦虑的作用。

更新日期：2024-03-19

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