Effects of tannins from Geum japonicum on the catalytic activity of thrombin and factor Xa of blood coagulation cascade
Effects of tannins from Geum japonicum on the catalytic activity of thrombin and factor Xa of blood coagulation cascade
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DOI：
10.1021/np9801458
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发表时间：
1998-11-01
影响因子：
5.1
通讯作者：
Xu, HX
中科院分区：
文献类型：
--
作者：
Dong, H;Chen, SX;Xu, HX
以生物测定为导向的分离方法分离出七种已知的丹宁。经波谱鉴定为5-O-没食子酰基-β-二葡萄糖苷(1)、马钱子素(2)、2，3-(S)-六羟基二苯酰-D-葡萄糖(3)、灯盏花素II(4)、2，6-二-O-没食子酰基-D-葡萄糖(5)、木麻黄素(6)和5-去没食子酰水苏糖苷(7)。化合物1、2、4、6和7通过显著延长兔血浆的凝血时间而显示出强大的抗凝血活性。2对凝血酶的抑制作用是竞争性的。其抑制合成底物和纤维蛋白原上凝血酶活性的IC50值分别为0.18和0.15 mU M。另一方面，化合物1、4、6和7是凝血酶的混合非竞争性抑制剂。其抑制纤维蛋白原水解物的IC50值比抑制合成底物水解物的IC50值低2~7倍。Xa因子被化合物1、2、4、6和7竞争性抑制。活性单宁的酚羟基似乎在它们对酶的抑制作用中起着重要作用。
Bioassay-guided fractionation of the MeOH extract of the whole plant of Geum japonicum led to the isolation of seven known tannins. They were identified by spectroscopic methods as penta-O-galloyl-beta-di-glucoside (1), pedunculagin (2), 2,3-(S)-hexahydroxydiphenoyl-D-glucose (3), tellimagrandin II (4), 2,6-di-O-galloyl-D-glucose (5), casuariin (6), and 5-desgalloylstachyurin (7). Compounds 1, 2, 4, 6, and 7 showed potent anticoagulant activity by significantly prolonging the clotting of rabbit plasma. The inhibitory effect of 2 was competitively directed against thrombin. Its IC50 values for inhibition of the enzymatic activity of thrombin on synthetic substrate and fibrinogen were 0.18 and 0.15 mu M, respectively. On the other hand, compounds 1, 4, 6, and 7 are mixed noncompetitive inhibitors of thrombin. Their IC50 values for inhibition of fibrinogen hydrolysis were twofold to sevenfold lower than those for the inhibition of synthetic substrate hydrolysis. Factor Xa was competitively inhibited by compounds 1, 2, 4, 6, and 7. The phenolic hydroxyl groups of the active tannins appear to play an important role in their inhibitory effect on the enzymes.