Novel anticoagulants and antithrombotic properties from Echinacea purpurea: A pharmacoinformatics and experimental insights

Thromboembolic disorders, including deep vein thrombosis, myocardial infarction, and stroke, remain leading causes of morbidity and mortality. Despite the availability of anticoagulant drugs, their associated bleeding risks and limitations necessitate the search for safer alternatives. Echinacea purpurea has been widely studied for its immunomodulatory properties, but its anticoagulant potential remains underexplored. This study employed metabolomic profiling, in silico analysis, and in vitro enzymatic assays to investigate the anticoagulant and antithrombotic properties of E. purpurea . Molecular docking and network pharmacology analyses were used to predict interactions with coagulation-related targets, while enzymatic assays assessed its effects on Factor IIa (Thrombin), Factor Xa, and Factor XIII. Metabolomic profiling identified bioactive compounds such as campesterol, chicoric acid, and caffeic acid. Campesterol exhibited strong binding affinity to SERPINE1, STAT3, and thromboxane A2 receptor, with a notable overall docking score of -39.4 kcal/mol, surpassing that of aspirin (-25.4 kcal/mol) and heparin (-32.7 kcal/mol). In vitro enzymatic assays confirmed significant and dose-dependent inhibition of thrombin (Factor IIa), Factor Xa, and Factor XIII (transglutaminase), with the E. purpurea extract demonstrating inhibition capacities comparable to heparin. Campesterol specifically exhibited a superior Factor Xa inhibition profile compared to the crude extract , alongside notable COX-2 inhibition and strong antioxidant activity. Echinacea purpurea demonstrates promising anticoagulant and antithrombotic effects via multiple mechanisms, suggesting its potential as a natural alternative to conventional therapies. This study, by integrating pharmacoinformatics, metabolomic profiling, and in vitro validation, offers the first comprehensive mechanistic insights into E. purpurea's direct anticoagulant potential, a novel contribution beyond its previously recognized immunomodulatory properties. Further in vitro and in vivo studies utilizing different animal models are needed to validate and confirm its safety and effective therapeutic applicability in preventing thrombotic diseases . • Metabolomic profiling pins campesterol, chicoric- and caffeic-acid as key Echinacea purpurea anticoagulants. • In-silico docking shows these phytochemicals out-bind aspirin and heparin at thrombin, FXa, FXIII active sites. • Crude extract blocks thrombin, Factor Xa & Factor XIII activities and suppresses COX-2 in cell-free assays. • Network pharmacology links >40 coagulation- and platelet-related targets to the identified compounds. • Findings position E. purpurea as a promising, multi-target nutraceutical for thrombosis prevention.