Antithrombotic ?in vivo? effects of quercetin 3,7,3?,4?-tetrasulfate isolated from Flaveria bidentis in an experimental thrombosis model in mice

Abstract

Thrombotic events are the major causes of morbidity and mortalityworldwide, with venous thromboembolism, heart attack and strokesbeing responsible for one in every four deaths [1]. Effective antithrombotictherapy has long been the basis of treatment for venous/arterialthromboembolic events and has reduced mortality rates from30% to 3-8%. Currently, there are many antithrombotic agents that canselectively interrupt pathological thrombin generation and the exaggeratedplatelet response, thus preventing the consequent thrombosis[2].Plants are abundant sources of novel bioactive compounds and, inparticular, flavonoids, a large group of naturally occurring compoundsisolated from certain plants, have been found to inhibit thrombus formation.This effect is most evident in compounds that contain a quercetinbackbone. Flaveria bidentis (L.) Kuntze, among others, biosynthesizesquercetin 3,7,3?,4?-tetrasulfate isolated (QTS) and quercetinquercetin 3-acetyl-7,3?,4?-trisulfate (ATS), the quercetin derivativeswith the highest degree of sulfation known so far [3]. Preliminarystudies in our laboratory showed that QTS, and to a lesser extent ATS,possess important anticoagulant, antiplatelet and profibrinolytic activities