Hydrolyzed Chicken Meat Extract and Its Bioactive Cyclopeptides Protect Neural Function by Attenuating Inflammation and Apoptosis via PI3K/AKT and AMPK Pathways,Journal of Agricultural and Food Chemistry

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Hydrolyzed Chicken Meat Extract and Its Bioactive Cyclopeptides Protect Neural Function by Attenuating Inflammation and Apoptosis via PI3K/AKT and AMPK Pathways
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-17 , DOI: 10.1021/acs.jafc.4c02063
Yinhua Ni ₁ , Zhaorong Wang ₁ , Fen Zhuge ₂ , Kexin Zhou ₁ , Liujie Zheng ₁ , Xinyang Hu ₁ , Sisi Wang ₁ , Ou Fu ₃ , Zhengwei Fu ₁

Affiliation

Cognitive decline is inevitable with age, and due to the lack of well-established pharmacotherapies for neurodegenerative disorders, dietary supplements have become important alternatives to ameliorate brain deterioration. Hydrolyzed chicken meat extract (HCE) and its bioactive components were previously found to improve neuroinflammation and cognitive decline by regulating microglia polarization. However, the effects and mechanisms of these bioactives on neurons remain unclear. Here, the most potent bioactive component on neural function in HCE was screened out, and the detailed mechanism was clarified through in vivo and in vitro experiments. We found that HCE, cyclo(Val-Pro), cyclo(Phe-Phe), cyclo(His-Pro), cyclo(Leu-Lys), and arginine exerted stronger anti-inflammatory and antioxidant effects among the 12 bioactives in amyloid β (Aβ)-treated HT-22 cells. Further transcriptome sequencing and polymerase chain reaction (PCR) array analysis showed that these bioactives participated in different signaling pathways, and cyclo(Val-Pro) was identified as the most potent cyclic dipeptide. In addition, the antiapoptotic and neuroprotective effect of cyclo(Val-Pro) was partly regulated by the activation of PI3K/AKT and AMPK pathways, and the inhibition of these pathways abolished the effect of cyclo(Val-Pro). Moreover, cyclo(Val-Pro) enhanced cognitive function and neurogenesis and alleviated neuroinflammation and oxidative stress in middle-aged mice, with an effect similar to HCE. Hippocampal transcriptome analysis further revealed that HCE and cyclo(Val-Pro) significantly enriched the neuroactive ligand–receptor interaction pathway, verified by enhanced neurotransmitter levels and upregulated neurotransmitter receptor-related gene expression. Therefore, the mechanism of cyclo(Val-Pro) on neural function might be associated with PI3K/AKT and AMPK pathway-mediated antiapoptotic effect and neurogenesis and the activation of the neurotransmitter-receptor pathway.

中文翻译：

水解鸡肉提取物及其生物活性环肽通过 PI3K/AKT 和 AMPK 途径减轻炎症和细胞凋亡，从而保护神经功能

随着年龄的增长，认知能力下降是不可避免的，由于缺乏针对神经退行性疾病的成熟药物疗法，膳食补充剂已成为改善大脑退化的重要替代品。此前发现水解鸡肉提取物（HCE）及其生物活性成分可以通过调节小胶质细胞极化来改善神经炎症和认知能力下降。然而，这些生物活性物质对神经元的影响和机制仍不清楚。在此，我们筛选出了HCE中对神经功能最有效的生物活性成分，并通过体内和体外实验阐明了详细的机制。我们发现β淀粉样蛋白中的12种生物活性物质中，HCE、环(Val-Pro)、环(Phe-Phe)、环(His-Pro)、环(Leu-Lys)和精氨酸具有更强的抗炎和抗氧化作用(Aβ) 处理的 HT-22 细胞。进一步的转录组测序和聚合酶链式反应（PCR）阵列分析表明，这些生物活性物质参与不同的信号通路，其中环（Val-Pro）被确定为最有效的环状二肽。此外，cyclo(Val-Pro)的抗凋亡和神经保护作用部分是通过PI3K/AKT和AMPK通路的激活来调节的，抑制这些通路可消除cyclo(Val-Pro)的作用。此外，环(Val-Pro)可增强中年小鼠的认知功能和神经发生，减轻神经炎症和氧化应激，其作用与HCE相似。海马转录组分析进一步表明，HCE 和 cyclo(Val-Pro) 显着丰富了神经活性配体-受体相互作用途径，这通过增强神经递质水平和上调神经递质受体相关基因表达得到证实。因此，cyclo(Val-Pro)对神经功能的作用机制可能与PI3K/AKT和AMPK通路介导的抗凋亡作用以及神经发生和神经递质受体通路的激活有关。

更新日期：2024-07-17

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