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Biflavones from Ginkgo biloba as inhibitors of human thrombin

文献类型：期刊论文

作者Chen, Tian-Ran2,3,4,5,6; Wei, Ling-Hua1,6; Guan, Xiao-Qing6; Huang, Chao6; Liu, Zhe-Yi8; Wang, Fang-Jun8; Hou, Jie7; Jin, Qiang6; Liu, Yi-Fan2,3,4,5; Wen, Pei-Hao2,3,4,5
刊名BIOORGANIC CHEMISTRY
出版日期2019-11-01
卷号92页码:10
关键词Ginkgo biloba Thrombin Proteolytic activity Biflavones Inhibitory effects
ISSN号0045-2068
DOI10.1016/j.bioorg.2019.103199
通讯作者Ge, Guang-Bo(geguangbo@dicp.ac.cn) ; Guo, Wen-Zhi(guowz66@163.com)
英文摘要Ginkgo Biloba leaf extract has been widely used for the prevention and treatment of thrombosis and cardiovascular disease in both eastern and western countries, but the bioactive constituents and the underlying mechanism of anti-thrombosis have not been fully characterized. The purpose of this study was to investigate the inhibitory effects of major constituents in Ginkgo biloba on human thrombin, a key serine protease regulating the blood coagulation cascade and the processes of thrombosis. To this end, a fluorescence-based biochemical assay was used to assay the inhibitory effects of sixteen major constituents from Ginkgo biloba on human thrombin. Among all tested natural compounds, four biflavones (ginkgetin, isoginkgetin, bilobetin and amentoflavone), and five flavonoids (luteolin, apigenin, quercetin, kaempferol and isorhamnetin) were found with thrombin inhibition activity, with the IC50 values ranging from 8.05 mu M to 82.08 mu M. Inhibition kinetic analyses demonstrated that four biflavones were mixed inhibitors against thrombin-mediated Z-GGRAMC acetate hydrolysis, with the K-i values ranging from 4.12 mu M to 11.01 mu M. Molecular docking method showed that the four biflavones could occupy the active cavity with strong interactions of salt bridges and hydrogen bonds. In addition, mass spectrometry-based lysine labeling reactivity assay suggested that the biflavones could bind on human thrombin at exosite I rather than exosite II. All these findings suggested that the biflavones in Ginkgo biloba were naturally occurring inhibitors of human thrombin, and these compounds could be used as lead compounds for the development of novel thrombin inhibitors with improved efficacy and high safety profiles.
WOS关键词PLATELET-ACTIVATING-FACTOR ; MOLECULAR-MECHANISMS ; EXTRACT ; CONSTITUENTS ; FLAVONOIDS ; BN-52021
资助项目National Natural Science Foundation of China[81922070] ; National Natural Science Foundation of China[81973286] ; National Natural Science Foundation of China[81671958] ; National Natural Science Foundation of China[U1604282] ; National Natural Science Foundation of China[U1504804] ; National Natural Science Foundation of China[81773687] ; National Natural Science Foundation of China[81571947] ; National Key Research and Development Program of China[2017YFC1700200] ; National Key Research and Development Program of China[2017YFC1702000] ; Program of Shanghai Academic/Technology Research Leader[18XD1403600] ; Shuguang Program[18SG40] ; Shanghai Education Development Foundation ; Technological and Innovative Project of Talent Support of University in Henan Province[19HASTIT003] ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation[142300410039] ; Medical Science and Technology Program of Henan Province[SBGJ2018002] ; Medical Science and Technology Program of Henan Province[SBGJ2018023] ; Shanghai Municipal Education Commission
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000489699400008
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
资助机构National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; Shuguang Program ; Shuguang Program ; Shanghai Education Development Foundation ; Shanghai Education Development Foundation ; Technological and Innovative Project of Talent Support of University in Henan Province ; Technological and Innovative Project of Talent Support of University in Henan Province ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Medical Science and Technology Program of Henan Province ; Medical Science and Technology Program of Henan Province ; Shanghai Municipal Education Commission ; Shanghai Municipal Education Commission ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; Shuguang Program ; Shuguang Program ; Shanghai Education Development Foundation ; Shanghai Education Development Foundation ; Technological and Innovative Project of Talent Support of University in Henan Province ; Technological and Innovative Project of Talent Support of University in Henan Province ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Medical Science and Technology Program of Henan Province ; Medical Science and Technology Program of Henan Province ; Shanghai Municipal Education Commission ; Shanghai Municipal Education Commission ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; Shuguang Program ; Shuguang Program ; Shanghai Education Development Foundation ; Shanghai Education Development Foundation ; Technological and Innovative Project of Talent Support of University in Henan Province ; Technological and Innovative Project of Talent Support of University in Henan Province ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Medical Science and Technology Program of Henan Province ; Medical Science and Technology Program of Henan Province ; Shanghai Municipal Education Commission ; Shanghai Municipal Education Commission ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; Shuguang Program ; Shuguang Program ; Shanghai Education Development Foundation ; Shanghai Education Development Foundation ; Technological and Innovative Project of Talent Support of University in Henan Province ; Technological and Innovative Project of Talent Support of University in Henan Province ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Basic and Frontier Technology Research Program of Henan Science and Technology Commission Foundation ; Medical Science and Technology Program of Henan Province ; Medical Science and Technology Program of Henan Province ; Shanghai Municipal Education Commission ; Shanghai Municipal Education Commission
源URL[http://cas-ir.dicp.ac.cn/handle/321008/172442]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Ge, Guang-Bo; Guo, Wen-Zhi
作者单位1.Taixing Peoples Hosp, 1 Changzheng Rd, Taixing 225400, Jiangsu, Peoples R China
2.Zhengzhou Univ, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Zhengzhou, Henan, Peoples R China
3.Henan Key Lab Digest Organ Transplantat, Zhengzhou, Henan, Peoples R China
4.Zhengzhou Key Lab Hepatobiliary & Pancreat Dis &, Zhengzhou, Henan, Peoples R China
5.Open & Key Lab Hepatobiliary & Pancreat Surg & Di, Zhengzhou 450001, Henan, Peoples R China
6.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China
7.Dalian Med Univ, Coll Basic Med Sci, Dalian 116044, Peoples R China
8.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		 Chen, Tian-Ran,Wei, Ling-Hua,Guan, Xiao-Qing,et al. Biflavones from Ginkgo biloba as inhibitors of human thrombin[J]. BIOORGANIC CHEMISTRY,2019,92:10.
APA Chen, Tian-Ran.,Wei, Ling-Hua.,Guan, Xiao-Qing.,Huang, Chao.,Liu, Zhe-Yi.,...&Guo, Wen-Zhi.(2019).Biflavones from Ginkgo biloba as inhibitors of human thrombin.BIOORGANIC CHEMISTRY,92,10.
MLA Chen, Tian-Ran,et al."Biflavones from Ginkgo biloba as inhibitors of human thrombin".BIOORGANIC CHEMISTRY 92(2019):10.

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来源：大连化学物理研究所

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