淫羊藿苷对乙酰胆碱酯酶的抑制作用

Inhibitory effect of icariin on acetylcholinesterase

乙酰胆碱酯酶(acetylcholinesterase,AChE)抑制剂是目前治疗阿尔茨海默病(Alzheimer’s disease,AD)的主要药物。本文应用酶抑制动力学方法研究了淫羊藿苷对AChE的抑制作用,并利用分子荧光光谱法和分子对接分别研究了淫羊藿苷与AChE之间的结合反应和结合位点。研究发现,淫羊藿苷对AChE的活性具有一定的抑制作用,测得的IC50为3.50×10 8mol.L 1(他克林的IC50测得值为0.75×10 8mol.L 1)。淫羊藿苷对AChE的抑制作用表现为混合型可逆抑制,抑制常数KI和KIS分别为2.67×10 8和4.43×10 8mol.L 1。淫羊藿苷主要通过氢键作用和分子间作用力结合于AChE的外周阴离子位点。

Acetylcholinesterase （ACHE） inhibitors are mainly used in the treatment of Alzheimer＇s disease （AD）. The inhibitory effect of icariin on the activity of AChE was investigated by inhibition kinetics. The binding interaction and binding sites between icariin and AChE were also studied by using fluorimetry and molecular docking, respectively. The results showed that icariin could potently inhibit the activity of ACHE, the IC50 value was determined to be 3.50x10-~ mol.L-~, and the determined ICs0 value to tacrine was 0.75x10-~ mol.L ~. Kinetic analyses showed that icariin is a reversible and mixed type AChE inhibitor. The inhibition constants K1 and K1s were determined to be 2.67×10-8 and 4.43×10-8 mol.L-1, respectively. Icariin binds selectively to the AChE peripheral anionic site via hydrogen bonds and Van der Waals forces.