College of Food and Biological Engineering, Jimei University, Xiamen 361021, China.
Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China.
Mar Drugs. 2022 Mar 31;20(4):247. doi: 10.3390/md20040247.
Alzheimer´s disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was evaluated by a chemical-based method in vitro and cell assay model. The results show that all-trans astaxanthin was a reversible competitive inhibitor and exhibited a strong inhibition effect with half inhibitory concentration (IC value) of 8.64 μmol/L. Furthermore, all-trans astaxanthin inhibited oxidative stress through reducing malondialdehyde content and increasing the activity of superoxide dismutase as well as catalase. All-trans astaxanthin could induce the changes of the secondary structure to reduce acetylcholinesterase activity. Molecular-docking analysis reveals that all-trans astaxanthin prevented substrate from binding to acetylcholinesterase by occupying the space of the active pocket to cause the inhibition. Our finding suggests that all-trans astaxanthin might be a nutraceutical supplement for Alzheimer´s disease prevention.
阿尔茨海默病是一种全球性的神经退行性健康问题。为了预防这种疾病,同时抑制乙酰胆碱酯酶和氧化应激是一种有效的方法。在这项研究中,通过体外化学方法和细胞测定模型评估了全反式虾青素(主要来自海洋生物)对乙酰胆碱酯酶和氧化应激的抑制作用。结果表明,全反式虾青素是一种可逆的竞争性抑制剂,具有很强的抑制作用,半数抑制浓度(IC 值)为 8.64 μmol/L。此外,全反式虾青素通过降低丙二醛含量和增加超氧化物歧化酶和过氧化氢酶的活性来抑制氧化应激。全反式虾青素可以诱导二级结构的变化,从而降低乙酰胆碱酯酶的活性。分子对接分析表明,全反式虾青素通过占据活性口袋的空间来阻止底物与乙酰胆碱酯酶结合,从而导致抑制。我们的研究结果表明,全反式虾青素可能是预防阿尔茨海默病的营养补充剂。