Axel Brahmantyo Maynardo Nugroho, Vincent Lau, Arditya Damarkusuma, Nurpudji Astuti Taslim, Juan Leonardo, Vito Anggarino Damay, Rony Abdi Syahputra, Happy Kurnia Permatasari, Raymond Rubianto Tjandrawinata, Evhy Apryani, Antonello Santini, Fahrul Nurkolis
Background/objectives: 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. Methods: 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. Results: 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. Conclusions: 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. © 2025 The Authors
Cardiac, Thoracic, and Vascular Surgery Study Program, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia; Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; Medical Research Center of Indonesia, Surabaya, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada-RS Sardjito, Yogyakarta, Indonesia; Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia; Citra Deli Kreasitama Ltd, Banten, 15124, Indonesia; Department of Cardiovascular Medicine, Universitas Pelita Harapan, Banten, Tangerang, 15811, Indonesia; Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia; Department of Biochemistry and Biomolecular, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Center for Pharmaceutical and Nutraceutical Research and Policy, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia; Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, 60131, Indonesia; Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano, 49 – 80131, Napoli, Italy; State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, Indonesia; Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
