DICP OpenIR
Biflavones from Ginkgo biloba as inhibitors of human thrombin
Chen, Tian-Ran1,2,3,4,5; Wei, Ling-Hua5,8; Guan, Xiao-Qing5; Huang, Chao5; Liu, Zhe-Yi7; Wang, Fang-Jun7; Hou, Jie6; Jin, Qiang5; Liu, Yi-Fan1,2,3,4; Wen, Pei-Hao1,2,3,4; Zhang, Shui-Jun1,2,3,4; Ge, Guang-Bo5; Guo, Wen-Zhi1,2,3,4
Corresponding AuthorGe, Guang-Bo(geguangbo@dicp.ac.cn) ; Guo, Wen-Zhi(guowz66@163.com)
KeywordGinkgo biloba Thrombin Proteolytic activity Biflavones Inhibitory effects
Source PublicationBIOORGANIC CHEMISTRY
2019-11-01
ISSN0045-2068
DOI10.1016/j.bioorg.2019.103199
Volume92Pages:10
Funding ProjectNational 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
Funding OrganizationNational 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
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Organic
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS KeywordPLATELET-ACTIVATING-FACTOR ; MOLECULAR-MECHANISMS ; EXTRACT ; CONSTITUENTS ; FLAVONOIDS ; BN-52021
AbstractGinkgo 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.
Language英语
Funding OrganizationNational 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
WOS IDWOS:000489699400008
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/172443
Collection中国科学院大连化学物理研究所
Corresponding AuthorGe, Guang-Bo; Guo, Wen-Zhi
Affiliation1.Zhengzhou Univ, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Zhengzhou, Henan, Peoples R China
2.Henan Key Lab Digest Organ Transplantat, Zhengzhou, Henan, Peoples R China
3.Zhengzhou Key Lab Hepatobiliary & Pancreat Dis &, Zhengzhou, Henan, Peoples R China
4.Open & Key Lab Hepatobiliary & Pancreat Surg & Di, Zhengzhou 450001, Henan, Peoples R China
5.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China
6.Dalian Med Univ, Coll Basic Med Sci, Dalian 116044, Peoples R China
7.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
8.Taixing Peoples Hosp, 1 Changzheng Rd, Taixing 225400, Jiangsu, Peoples R China
Recommended Citation
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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