Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.
College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.
Inflammopharmacology. 2024 Dec;32(6):3745-3759. doi: 10.1007/s10787-024-01570-4. Epub 2024 Sep 21.
Alzheimer's disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aβ in glial (BV-2 and SW-1783) and neuron (SH-SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA-Trpv1-Nrf2 pathway.
阿尔茨海默病（AD）是一种神经退行性疾病，常伴有神经炎症和氧化应激。药食同源（MFH）已显示出治疗神经炎症和氧化应激的潜力。本研究旨在基于 MFH 为 AD 提供一种安全有效的治疗方法。在本研究中，我们开发了一种由蛋黄油、紫苏籽油、萝卜籽油、肉桂油和诺丽果泥组成的 MFH 配方（EPRCN）。为了评估 EPRCN 对 AD 相关症状的改善作用，我们使用腹腔注射东莨菪碱构建了 AD 小鼠模型。实验结果表明，EPRCN 补充剂可恢复行为缺陷，并抑制东莨菪碱诱导的小鼠海马中的神经炎症和氧化应激。然后，通过诱导神经胶质（BV-2 和 SW-1783）和神经元（SH-SY5Y）细胞系中的 Aβ，进行了体外研究，以检查 EPRCN 对认知缺陷的改善机制。多组学和体外研究表明，这些变化是由大麻素（AEA）-TRPV1-Nrf2 通路驱动的，AEA 抑制剂 AM404、TRPV1 抑制剂 AMG9810 和 Nrf2 抑制剂 BT 可抑制该通路。因此，EPRCN 是预防 AD 小鼠模型认知缺陷的有效治疗方法。与多奈哌齐不同，EPRCN 表现出改善神经炎症的新作用模式。EPRCN 预防认知缺陷的机制是通过激活 AEA-Trpv1-Nrf2 通路来改善神经炎症和氧化应激。
