Salvianolic acid B inhibits thrombosis and directly blocks the thrombin catalytic site

作者：Miguel A. D. Neves, Tiffany Ni, Daniel Thomas MacKeigan, Aron A. Shoara, Xi Lei, Sladjana Slavkovic, Siyang Yu, Tyler W. Stratton, Reid C. Gallant, Dan Zhang, Xiaohong Xu, Cheryl Fernandes, Guangheng Zhu, Xudong Hu, Noa Chazot, Logan W. Donaldson, Philip E. Johnson, Kim A. Connelly, Margaret L. Rand, Yiming Wang, Heyu Ni · 发表于：Research and Practice in Thrombosis and Haemostasis · 年份：2024 · DOI：10.1016/j.rpth.2024.102443 · 被引用次数：19 · 研究领域：Traditional Chinese Medicine Analysis、Plant-based Medicinal Research、Ginseng Biological Effects and Applications

Background Salvianolic acid B (SAB) is a major component of Salvia miltiorrhiza root (Danshen), widely used in East/Southeast Asia for centuries to treat cardiovascular diseases. Danshen depside salt, 85% of which is made up of SAB, is approved in China to treat chronic angina. Although clinical observations suggest that Danshen extracts inhibited arterial and venous thrombosis, the exact mechanism has not been adequately elucidated. Objective To delineate the antithrombotic mechanisms of SAB. Methods We applied platelet aggregation and coagulation assays, perfusion chambers, and intravital microscopy models. The inhibition kinetics and binding affinity of SAB to thrombin are measured by thrombin enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. We used molecular in silico docking models to predict the interactions of SAB with thrombin. Results SAB dose-dependently inhibited platelet activation and aggregation induced by thrombin. SAB also reduced platelet aggregation induced by adenosine diphosphate and collagen. SAB attenuated blood coagulation by modifying fibrin network structures and significantly decreased thrombus formation in mouse cremaster arterioles and perfusion chambers. The direct SAB-thrombin interaction was confirmed by enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. Interestingly, SAB shares key structural similarities with the trisubstituted benzimidazole class ...