Molecular docking-assisted screening reveals tannic acid as a natural protein disulphide isomerase inhibitor with antiplatelet and antithrombotic activities.
Molecular docking-assisted screening reveals tannic acid as a natural protein disulphide isomerase inhibitor with antiplatelet and antithrombotic activities.
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分子对接辅助筛选揭示单宁酸是一种天然蛋白质二硫化物异构酶抑制剂，具有抗血小板和抗血栓形成活性
DOI：
10.1111/jcmm.16043
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发表时间：
2020-12
影响因子：
5.3
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Ren L;You T;Li Q;Chen G;Liu Z;Zhao X;Wang Y;Wang L;Wu Y;Tang C;Zhu L
蛋白二硫异构酶（PDI）促进血小板活化和构成一个新的抗血栓靶点。在这项研究中，我们报道了一种结合PDI的植物多酚，单宁酸（TA），抑制PDI活性，血小板活化和血栓形成。利用具有心血管益处的膳食来源的植物多酚进行分子对接，发现TA是与PDI活性中心最有效的结合分子。表面等离子体共振表明TA与PDI具有高亲和力。利用二-伊红-谷胱甘肽二硫荧光法和PDI检测试剂盒，我们发现TA抑制PDI活性。在分离的血小板中，TA抑制GPVI或ITAM途径激动剂刺激的血小板聚集。流式细胞术显示TA抑制凝血酶或CRP刺激的血小板活化，反映在减少颗粒分泌和整合素活化上。在流动条件下，TA还能减少血小板在固定纤维蛋白原上的扩散和血小板粘附。在激光诱导的血管损伤小鼠模型中，腹腔注射TA可显著降低微动脉血栓的大小。给药后小鼠颈静脉未见延长，尾出血时间未见延长。因此，我们从天然多酚中鉴定出TA作为PDI功能的新型抑制剂。TA抑制血小板活化和血栓形成，提示它是一种潜在的抗血栓药物。
Protein disulphide isomerase (PDI) promotes platelet activation and constitutes a novel antithrombotic target. In this study, we reported that a PDI‐binding plant polyphenol, tannic acid (TA), inhibits PDI activity, platelet activation and thrombus formation. Molecular docking using plant polyphenols from dietary sources with cardiovascular benefits revealed TA as the most potent binding molecule with PDI active centre. Surface plasmon resonance demonstrated that TA bound PDI with high affinity. Using Di‐eosin‐glutathione disulphide fluorescence assay and PDI assay kit, we showed that TA inhibited PDI activity. In isolated platelets, TA inhibited platelet aggregation stimulated by either GPVI or ITAM pathway agonists. Flow cytometry showed that TA inhibited thrombin‐ or CRP‐stimulated platelet activation, as reflected by reduced granule secretion and integrin activation. TA also reduced platelet spreading on immobilized fibrinogen and platelet adhesion under flow conditions. In a laser‐induced vascular injury mouse model, intraperitoneal injection of TA significantly decreased the size of cremaster arteriole thrombi. No prolongation of mouse jugular vein and tail‐bleeding time was observed after TA administration. Therefore, we identified TA from natural polyphenols as a novel inhibitor of PDI function. TA inhibits platelet activation and thrombus formation, suggesting it as a potential antithrombotic agent.
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影响因子：
3.2
作者：
Essex DW;Wu Y
通讯作者：
Wu Y
DOI：
10.1161/atvbaha.114.303410
发表时间：
2015-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Flaumenhaft R;Furie B;Zwicker JI
通讯作者：
Zwicker JI
影响因子：
14.9
作者：
Kim S;Thiessen PA;Bolton EE;Chen J;Fu G;Gindulyte A;Han L;He J;He S;Shoemaker BA;Wang J;Yu B;Zhang J;Bryant SH
通讯作者：
Bryant SH
影响因子：
7.2
作者：
Hu, Xitian;Wang, Hua;Cui, Wei
通讯作者：
Cui, Wei
影响因子：
20.3
作者：
Kim, Kyungho;Hahm, Eunsil;Cho, Jaehyung
通讯作者：
Cho, Jaehyung