期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 134, 期 -, 页码 622-630出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2019.04.181
关键词
Thrombin; Proteolytic activity; Hypericin; St. John's wort; Inhibitory effects
资金
- National Key Research and Development Program of China [2016YFC1303900, 2017YFC1700200, 2017YFC1702000]
- National Natural Science Foundation of China [81671958, 81803489, U1604282, 81773687]
- Program of Shanghai Academic/technology Research Leader [18XD1403600]
- Shanghai Education Development Foundation [18SG40]
- Shanghai Municipal Education Commission [18SG40]
- Scientific and Technological Project of Science and Technology Department of Henan Province [340600531842, 152300413242]
- Medical Science and Technological Program of Henan Province [201401003, SBGJ2018002, SBGJ2018023]
- The Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation [142300410039]
Thrombin, a multifunctional serine protease responsible for the proteolytic hydrolysis of soluble fibrinogen, plays a pivotal role in the blood coagulation cascade. Currently, thrombin inhibitor therapy has been recognized as an effective therapeutic strategy for the prevention and treatment of thrombotic diseases. In this study, the inhibitory effects of natural constituents in St. John's Wort against human thrombin are carefully investigated by a fluorescence-based biochemical assay. The results clearly demonstrate that most of naphthodianthrones, flavonoids and biflavones exhibit strong to moderate inhibition on human thrombin. Among all tested compounds, hypericin shows the most potent inhibitory capability against thrombin, with the IC50 value of 3.00 mu M. Further investigation on inhibition kinetics demonstrates that hypericin is a potent and reversible inhibitor against thrombin-mediated Z-GGRAMC acetate hydrolysis, with the K-i value of 2.58 mu M. Inhibition kinetic analyses demonstrate that hypericin inhibits thrombin-mediated Z-GGRAMC acetate hydrolysis in a mixed manner, which agrees well with the results from docking simulations that hypericin can bind on both catalytic cavity and anion binding exosites. All these findings suggest that hypericin is a natural thrombin inhibitor with a unique dianthrone skeleton, which can be used as a good candidate to develop novel thrombin inhibitors with improved properties. (C) 2019 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据