Experimental study on anticoagulant and antiplatelet aggregation activity of a chemically sulfated marine polysaccharide YCP.
A polysaccharide YCP was prepared from a marine filamentous fungus Keissleriella sp. YS4108, which exhibited as a molecular weight (Mw) of 2.4x10(3) kDa and its three sulfated derivatives (YCP-SL, YCP-SM and YCP-SH) were synthesized, the degree of substitution (DS) of which were determined to be 0.13, 0.99 and 1.3, with the average molecular weight 0.64x10(3), 0.57x10(3) and 0.45x10(3) kDa, respectively. Anticoagulant activity and antiplatelet aggregation activity of these sulfated derivates were evaluated by activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and platelet aggregation assay. The results showed that YCP sulfates significantly prolonged APTT, TT and PT. The derivates showed no effects on thrombin in the presence or in the absence of antithrombin III (AT III) or heparin cofactor II (HC II), while the derivates effectively inhibited factor Xa in the presence of AT III. At the same time, YCP-SH also possessed potent antiplatelet aggregation activity in vitro compared with aspirin. YCP sulfates specifically interfered with different stages of the coagulation cascade, and the anticoagulant activity improved with the increasing DS and decreased Mw.
Han
Fang
F
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
Yao
Wenbing
W
Yang
Xiaobing
X
Liu
Xiaoni
X
Gao
Xiangdong
X
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000276:immunology; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry; D005559:Formamides / Q000737:chemistry; D005658:Fungi; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology; D011517:Prothrombin Time; D011725:Pyridines / Q000737:chemistry; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D013431:Sulfates / Q000737:chemistry; D013451:Sulfonic Acids / Q000737:chemistry; D013463:Sulfuric Acid Esters; D013917:Thrombin / Q000737:chemistry; D013918:Thrombin Time
D000906:Antibodies; D000925:Anticoagulants; D005559:Formamides; D011134:Polysaccharides; D011725:Pyridines; D013431:Sulfates; D013451:Sulfonic Acids; D013463:Sulfuric Acid Esters; C013880:chlorosulfonic acid; C031066:formamide; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin; D015951:Factor Xa; C023666:pyridine; D001241:Aspirin