Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan, 316022, China.
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen, 361102, China.
Neurochem Res. 2024 Jun;49(6):1592-1602. doi: 10.1007/s11064-024-04107-x. Epub 2024 Feb 2.
In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO)-1→4-α-L-fucp(2,3-SO)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.
在本研究中，通过酶辅助提取法用三种食品级酶消化裙带菜获得了硫酸多糖，并研究了其抗阿尔茨海默病的活性。结果表明，用 AMGSP、CSP 和 VSP 提取的粗硫酸多糖在 Y 迷宫实验中呈剂量依赖性（25-100µg·mL）提高了小鼠的自发交替方式（%），并降低了 Morris 水迷宫试验中的逃逸潜伏期。AMGSP、CSP 和 VSP 还表现出良好的抗 AChE 和适度的抗 BuChE 活性。CSP 对 AChE 的抑制作用最好，IC 值为 9.77µM。此外，CSP 对 AChE 也表现出良好的抑制选择性。接下来，用制备型高效液相色谱法对最佳活性粗提物的 CSP 进行分离，得到硫酸岩藻糖寡糖部分：SFcup（→3-α-L-岩藻糖（2-SO）-1→4-α-L-岩藻糖（2,3-SO）-1→部分），SFcup 对 AChE 的抑制作用最好，IC 值为 4.03µM。动力学研究表明，SFcup 通过双重结合位点抑制 AChE。此外，SFcup 在 AChE 活性部位的分子对接与获得的药理结果一致。
