Shi Cheng-Cheng, Chen Tian-Ran, Zhang Qi-Hua, Wei Ling-Hua, Huang Chao, Zhu Ya-Di, Liu Hai-Bin, Bai Ya-Kun, Wang Fang-Jun, Guo Wen-Zhi, Zhang Li-Rong, Ge Guang-Bo
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University Zhengzhou Henan China
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine Shanghai China
RSC Adv. 2020 Jan 22;10(7):3626-3635. doi: 10.1039/c9ra09203j.
Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks blocking the formation of blood clots. This study aimed to identify naturally occurring thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhibitory mechanisms. Among all tested licorice constituents, licochalcone A was found as the most efficacious agent against human thrombin (IC = 7.96 μM). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin-mediated -Gly-Gly-Arg-AMC acetate hydrolysis, with a value of 12.23 μM. Furthermore, mass spectrometry-based chemoproteomic assays and molecular docking simulations revealed that licochalcone A could bind to human thrombin at both exosite I and the catalytic site. In summary, our findings demonstrated that the chalcones isolated from licorice were a new class of direct thrombin inhibitors, also suggesting that licochalcone A was a promising lead compound for developing novel anti-thrombotic agents.
凝血酶抑制疗法是一种通过阻止血凝块形成来降低血栓形成和心血管疾病风险的实用策略。本研究旨在从甘草（最受欢迎的可食用草药之一）中鉴定天然存在的凝血酶抑制剂，并研究其抑制机制。在所有测试的甘草成分中，光甘草定被发现是对人凝血酶最有效的抑制剂（IC = 7.96 μM）。抑制动力学分析表明，光甘草定是一种针对凝血酶介导的 -Gly-Gly-Arg-AMC 乙酸盐水解的混合型抑制剂， 值为 12.23 μM。此外，基于质谱的化学蛋白质组学分析和分子对接模拟表明，光甘草定可以在人凝血酶的外位点 I 和催化位点处与之结合。总之，我们的研究结果表明，从甘草中分离出的查耳酮是一类新型的直接凝血酶抑制剂，这也表明光甘草定是开发新型抗血栓药物的一种有前景的先导化合物。
