Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies

doi:10.1039/c9ra09203j

	Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies
	Shi, Cheng-Cheng 2,3; Chen, Tian-Ran 3,4,5; Zhang, Qi-Hua 6; Wei, Ling-Hua 1; Huang, Chao 3; Zhu, Ya-Di 3; Liu, Hai-Bin 4; Bai, Ya-Kun 1; Wang, Fang-Jun 7; Guo, Wen-Zhi 1
刊名	RSC ADVANCES
	2020-01-23
卷号	10 期号:7 页码:3626-3635
DOI	10.1039/c9ra09203j
通讯作者	Guo, Wen-Zhi(guowz66@163.com) ; Zhang, Li-Rong(zhanglirongzzu@126.com) ; Ge, Guang-Bo(geguangbo@dicp.ac.cn)
英文摘要	Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks via 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 (IC50 = 7.96 mu M). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin-mediated Z-Gly-Gly-Arg-AMC acetate hydrolysis, with a K-i value of 12.23 mu M. 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.
资助项目	National Key Research and Development Program of China[2017YFC1700200] ; National Key Research and Development Program of China[2017YFC1702000] ; National Natural Science Foundation of China[81973286] ; National Natural Science Foundation of China[81803489] ; National Natural Science Foundation of China[U1604282] ; National Natural Science Foundation of China[81973393] ; National Natural Science Foundation of China[81922070] ; National Natural Science Foundation of China[81773687] ; Program of Shanghai Academic/Technology Research Leader[18XD1403600] ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation[142300410039] ; TaiShan Industrial Experts Program[tscy20180234]
WOS关键词	TRADITIONAL CHINESE MEDICINE ; BIOACTIVE CONSTITUENTS ; BIOLOGICAL EVALUATION ; CHALCONE DERIVATIVES ; DESIGN ; DISCOVERY ; POTENT ; LICOCHALCONE ; FLAVONOIDS ; ACID
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000509900800001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281654]
专题	中国科学院上海药物研究所
通讯作者	Guo, Wen-Zhi; Zhang, Li-Rong; Ge, Guang-Bo
作者单位	1.Zhengzhou Univ, Henan Key Lab Digest Organ Transplantat, Dept Hepatobiliary & Pancreat Surg, Affiliated Hosp 1, Zhengzhou, Peoples R China 2.Zhengzhou Univ, Sch Basic Med Sci, Dept Pharmacol, Zhengzhou, Henan, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai, Peoples R China 4.Dong E E Jiao Co Ltd, Natl Engn Res Ctr Gelatin Based Tradit Chinese Me, Shandong, Peoples R China 5.Zhengzhou Univ, Affiliated Hosp 5, Dept Gastrointestinal Surg, Zhengzhou, Peoples R China 6.Chinese Acad Sci, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai, Peoples R China 7.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Shi, Cheng-Cheng,Chen, Tian-Ran,Zhang, Qi-Hua,et al. Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies[J]. RSC ADVANCES,2020,10(7):3626-3635.
APA	Shi, Cheng-Cheng.,Chen, Tian-Ran.,Zhang, Qi-Hua.,Wei, Ling-Hua.,Huang, Chao.,...&Ge, Guang-Bo.(2020).Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies.RSC ADVANCES,10(7),3626-3635.
MLA	Shi, Cheng-Cheng,et al."Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies".RSC ADVANCES 10.7(2020):3626-3635.