Aihaiti Mayile, Shi Haidan, Liu Yaojie, Hou Chen, Song Xiaoyu, Li Mengting, Li Jianke
College of Food Engineering and Nutritional Science Shaanxi Normal University Xi'an China.
University Key Laboratory of Food Processing Byproducts for Advanced Development and High Value Utilization, Shaanxi Normal University Xi'an China.
Food Sci Nutr. 2023 Jul 6;11(10):5989-5998. doi: 10.1002/fsn3.3533. eCollection 2023 Oct.
Nervonic acid (NA) is a kind of ultra-long-chain monounsaturated fatty acid, which can repair nerve cell damage caused by oxidative stress. Alzheimer's disease (AD) is a nervous system disease and often accompanied by the decline of learning and memory capacity. In this study, the combined dose of D-galactose/AlCl was used to establish a mouse model of AD. Meanwhile, the mice were treated with different doses of NA (10.95 and 43.93 mg/kg). The results showed that NA delayed the decline of locomotion and learning ability caused by D-galactose/AlCl, increased the activity of total superoxide dismutase, catalase, glutathione peroxidase, and reduced the content of malondialdehyde in vivo. Besides, NA reduced the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), aspartate aminotransferase, alanine aminotransferase, increased the levels of 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, alleviated the cell morphology damage induced by D-galactose/AlCl in hippocampus and liver tissue. Furthermore, the intervention of NA upregulated the expression levels of PI3K, AKT, and mTOR genes and downregulated the expression levels of TNF-α, IL-6, and IL-1β genes. Therefore, we speculate the intervention of NA could be an effective way in improving cognitive impairment through the activation of PI3K signaling pathway. These results suggest that NA has the potential to be developed as antioxidant drug for the prevention and early therapy of AD.
神经酸（NA）是一种超长链单不饱和脂肪酸，能够修复由氧化应激引起的神经细胞损伤。阿尔茨海默病（AD）是一种神经系统疾病，常伴有学习和记忆能力的衰退。在本研究中，采用D-半乳糖/氯化铝联合给药的方式建立AD小鼠模型。同时，用不同剂量的NA（10.95和43.93mg/kg）对小鼠进行处理。结果显示，NA延缓了D-半乳糖/氯化铝所致的运动和学习能力衰退，提高了体内总超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶的活性，并降低了丙二醛含量。此外，NA降低了白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、天冬氨酸转氨酶、丙氨酸转氨酶的水平，提高了5-羟色胺、多巴胺、γ-氨基丁酸的水平，减轻了D-半乳糖/氯化铝诱导的海马和肝组织细胞形态损伤。进一步研究发现，NA干预上调了PI3K、AKT和mTOR基因的表达水平，下调了TNF-α、IL-6和IL-1β基因的表达水平。因此，我们推测NA的干预可能是通过激活PI3K信号通路改善认知障碍的有效途径。这些结果表明，NA有潜力被开发为预防和早期治疗AD的抗氧化药物。
