Effects of Native Fucosylated Glycosaminoglycan, Its Depolymerized Derivatives on Intrinsic Factor Xase, Coagulation, Thrombosis, and Hemorrhagic Risk
Zhou, Lutan1,2,3; Gao, Na4; Sun, Huifang2,3; Xiao, Chuang5,6; Yang, Lian2; Lin, Lisha2,3; Yin, Ronghua2; Li, Zi2; Zhang, Hongbin1; Ji, Xu1,7; Zhao, Jinhua2,4
Corresponding AuthorZhang, Hongbin(zhanghb@ynu.edu.cn) ; Ji, Xu(jixu@ynu.edu.cn) ; Zhao, Jinhua(zhao.jinhua@yahoo.com)
2020-04-01
Source PublicationTHROMBOSIS AND HAEMOSTASIS
ISSN0340-6245
Volume120Issue:4Pages:607-619
AbstractA native fucosylated glycosaminoglycan from sea cucumber Holothuria fuscopunctata (nHG), mainly branched with Fuc (3S4S) , exhibited potent anticoagulant activity by intrinsic tenase iXase (FIXa-FVIIIa complex) and antithrombin-dependent factor IIa (FIIa) inhibition, but also had the effects of FXII activation and platelet aggregation. For screening a selective iXase inhibitor, depolymerized nHG (dHG-1 similar to -6) and a pure octasaccharide (oHG-8) were prepared. Like nHG, dHG-1 similar to -6 and oHG-8 could potently inhibit iXase, and competitive binding assay indicated that dHG-5 and oHG-8 could bind to FIXa. Nevertheless, dHG-5 and oHG-8 had no effects on FXII and platelet activation. nHG, dHG-5, and oHG-8 could significantly prolong the activated partial thromboplastin time of human, rat, and rabbit plasma. In the rat deep venous thrombosis model, dHG-5 and oHG-8 showed potent antithrombotic effects in a dose-dependent manner, while the thrombus inhibition rate of nHG at high dose was markedly reduced. Additionally, dHG-5 and oHG-8 did not increase bleeding at the doses up to 10-fold of the effectively antithrombotic doses compared with nHG and low molecular weight heparin in the mice tail-cut model. Considering that dHG-5 possesses strong anti-iXase and antithrombotic activities, and its preparation process is simpler and its yield is higher compared with oHG-8, it might be a promising antithrombotic candidate.
KeyworddHG-5 iXase anticoagulant antithrombotic hemorrhagic risk
DOI10.1055/s-0040-1708480.
Indexed BySCI ; SCI
Language英语
WOS Research AreaHematology ; Cardiovascular System & Cardiology
WOS SubjectHematology ; Peripheral Vascular Disease
WOS IDWOS:000526907600009
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/71608
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorZhang, Hongbin; Ji, Xu; Zhao, Jinhua
Affiliation1.Yunnan Univ, Sch Chem Sci & Technol, Minist Educ & Yunnan Prov, Key Lab Med Chem Nat Resource, Kunming 650091, Yunnan, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, 132 Lanhei Rd, Kunming 650201, Yunnan, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.South Cent Univ National, Sch Pharmaceut Sci, Wuhan, Peoples R China
5.Kunming Med Univ, Sch Pharmaceut Sci, Kunming, Yunnan, Peoples R China
6.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming, Yunnan, Peoples R China
7.Suzhou Banbutang Biol Technol Co LTD, Suzhou, Peoples R China
Recommended Citation
GB/T 7714
Zhou, Lutan,Gao, Na,Sun, Huifang,et al. Effects of Native Fucosylated Glycosaminoglycan, Its Depolymerized Derivatives on Intrinsic Factor Xase, Coagulation, Thrombosis, and Hemorrhagic Risk[J]. THROMBOSIS AND HAEMOSTASIS,2020,120(4):607-619.
APA Zhou, Lutan.,Gao, Na.,Sun, Huifang.,Xiao, Chuang.,Yang, Lian.,...&Zhao, Jinhua.(2020).Effects of Native Fucosylated Glycosaminoglycan, Its Depolymerized Derivatives on Intrinsic Factor Xase, Coagulation, Thrombosis, and Hemorrhagic Risk.THROMBOSIS AND HAEMOSTASIS,120(4),607-619.
MLA Zhou, Lutan,et al."Effects of Native Fucosylated Glycosaminoglycan, Its Depolymerized Derivatives on Intrinsic Factor Xase, Coagulation, Thrombosis, and Hemorrhagic Risk".THROMBOSIS AND HAEMOSTASIS 120.4(2020):607-619.
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