N-Acetylneuraminic acid is a sialic acid naturally present in the colon. As a key component of cell surface glycoproteins and glycolipids, N-Acetylneuraminic acid participates in cell recognition, signal transduction, and adhesion. N-Acetylneuraminic acid can bind to pathogens, preventing their adhesion and invasion of host cells, thereby exerting antiviral and antibacterial effects, while enhancing immune function by regulating immune cell activity. N-Acetylneuraminic acid can be used in infant formula, functional foods and health products, as well as in research related to anti-influenza drugs and coronary heart disease[1-4].
In vitro, After 8 hours of hypoxia and glucose deprivation, H9C2 cardiomyocytes were treated with N-Acetylneuraminic acid (30mM) for 3 hours under reoxygenation conditions. N-Acetylneuraminic acid significantly increased superoxide dismutase (SOD) activity, elevated intracellular Fe²⁺ and lipid peroxide levels, reduced the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter (xCT), heme oxygenase-1 (HO-1), and ferroptosis suppressor protein 1 (FSP1), and promoted ferroptosis in cardiomyocytes[5]. N-Acetylneuraminic acid (20mM) was used to treat HUVECs for 24 hours. N-Acetylneuraminic acid significantly inhibited cell viability and increased the apoptosis rate, upregulated the protein and mRNA expression of inflammatory markers ICAM-1 and IL-1β, and decreased the levels of autophagy-related proteins LC3 II and SQSTM1/p62[6].
In vivo, N-Acetylneuraminic acid (500mg/kg) was subcutaneously injected twice daily into 5xFAD mice for 7 days. N-Acetylneuraminic acid replicated the effects of a high-fat diet on CD4⁺ T cells and accelerated recognition memory impairment[7]. N-Acetylneuraminic acid (60mg/kg/day) was intraperitoneally injected into high-fat diet-induced ApoE⁻/⁻ mice for five consecutive weeks. N-Acetylneuraminic acid significantly aggravated atherosclerotic lesions in mice, including increased lipid deposition, enlarged plaque necrotic core area, enhanced expression of pro-inflammatory cytokines and oxidative stress, and drove macrophage polarization toward a pro-inflammatory M1 phenotype[8].
References:
[1] Zhang L, Wei TT, Li Y, et al. Functional Metabolomics Characterizes a Key Role for N-Acetylneuraminic Acid in Coronary Artery Diseases. Circulation. 2018 Mar 27;137(13):1374-1390.
[2] Yida Z, Imam MU, Ismail M, et al. High fat diet-induced inflammation and oxidative stress are attenuated by N-acetylneuraminic acid in rats. J Biomed Sci. 2015 Oct 24;22:96.
[3] Kiefel MJ, Beisner B, Bennett S, et al. Synthesis and biological evaluation of N-acetylneuraminic acid-based rotavirus inhibitors. J Med Chem. 1996 Mar 15;39(6):1314-20.
[4] Bian D, Wang X, Huang J, et al. Maternal Neu5Ac Supplementation During Pregnancy Improves Offspring Learning and Memory Ability in Rats. Front Nutr. 2021 Oct 13;8:641027.
[5] Ji C, Zuo Z, Wang J, et al. N-acetylneuraminic acid promotes ferroptosis of H9C2 cardiomyocytes with hypoxia/reoxygenation injury by inhibiting the Nrf2 axis. Nan Fang Yi Ke Da Xue Xue Bao. 2025 Jan 20;45(1):72-79.
[6] Chen L, Qiu H, Chen Q, et al. N-acetylneuraminic acid modulates SQSTM1/p62 sialyation-mediated ubiquitination degradation contributing to vascular endothelium dysfunction in experimental atherosclerosis mice. IUBMB Life. 2024 Mar;76(3):161-178.
[7] Suzzi S, Croese T, Ravid A, et al. N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer's disease mouse model. Nat Commun. 2023 Mar 9;14(1):1293.
[8] Huang D, Yin C, Wang D. Neu5Ac promotes high-fat diet-induced progression of atherosclerosis in Apoe-deficient mice. Exp Anim. 2025 Dec 3.
N-Acetylneuraminic acid是一种天然存在于结肠中的唾液酸。N-Acetylneuraminic acid作为细胞表面糖蛋白和糖脂的关键组成成分，参与细胞识别、信号传导与黏附。N-Acetylneuraminic acid能够与病原体结合阻止其黏附和入侵宿主细胞，从而发挥抗病毒和抗菌作用，同时通过调节免疫细胞活性增强机体免疫功能。N-Acetylneuraminic acid可用于婴幼儿配方食品、功能性食品与保健品，以及抗流感药物和冠心病相关研究[1-4]。
在体外，缺氧缺糖8h后，在复氧的条件下，N-Acetylneuraminic acid（30mM）处理H9C2心肌细胞3h。N-Acetylneuraminic acid显著提高超氧化物歧化酶（SOD）活性，增加细胞内Fe²⁺和脂质过氧化物水平，降低核因子E2相关因子2（Nrf2）、谷胱甘肽过氧化物酶4（GPX4）、胱氨酸/谷氨酸反向转运体（xCT）、血红素加氧酶-1（HO-1）和铁死亡抑制蛋白1（FSP1）蛋白的表达，并促进心肌细胞发生铁死亡[5]。N-Acetylneuraminic acid（20mM）处理HUVECs细胞24小时。N-Acetylneuraminic acid显著抑制细胞活力并增加细胞凋亡率，同时上调炎症标志物ICAM-1和IL-1β的蛋白及mRNA表达，并降低自噬相关蛋白LC3 II和SQSTM1/p62的水平[6]。
在体内，N-Acetylneuraminic acid（500mg/kg）每天两次皮下注射于5xFAD小鼠，持续7天。N-Acetylneuraminic acid重现了高脂饮食对CD4+ T细胞的影响并加速了识别记忆障碍[7]。N-Acetylneuraminic acid（60mg/kg/day）腹腔注射于高脂饮食诱导的ApoE-/-小鼠，连续五周。N-Acetylneuraminic acid显著加重了小鼠动脉粥样硬化病变，增加脂质沉积、扩大斑块坏死核心面积、增强促炎细胞因子表达和氧化应激，并驱动巨噬细胞向促炎M1表型极化[8]。