A defined isothiocyanate mixture suppresses platelet signaling and metabolism to limit thrombosis in vivo
5 affiliations
- 1Department of Otorhinolaryngology, TUM School of Medicine and Health, Technical University of Munich (TUM) , ,
- 2Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz , ,
- 3Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health , ,
- 4Section Radiation Biology, Federal Office for Radiation Protection (BfS) , ,
- 5Central Institute for Translational Cancer Research, Technical University of Munich (TranslaTUM), Klinikum rechts der Isar , ,
Abstract
Pathological platelet activation drives thrombosis and is a major contributor to morbidity and mortality. Current antiplatelet therapies reduce thrombotic risk but target a limited range of signaling pathways, have minimal impact on established platelet aggregates, and are frequently associated with bleeding complications. These drawbacks have prompted interest in alternative antiplatelet strategies. Isothiocyanates (ITCs), phytochemicals from cruciferous plants, have been reported to inhibit platelet function; however, their mechanisms and translational relevance remain incompletely defined. The effects of a defined mixture of allyl-, benzyl-, and phenethyl-isothiocyanate on platelet function were evaluated using ex vivo human platelets and an in vivo murine model of carrageenan-induced thrombosis. Platelet aggregation, intracellular signaling, calcium mobilization, redox balance, and mitochondrial function were assessed using functional assays, kinome profiling, flow cytometry, respirometry, and electron microscopy. The ITC mixture was administered before or after the carrageenan challenge. The ITC mixture inhibited platelet activation and aggregation induced by multiple agonists. It reduced peptide phosphorylation across multiple platelet signaling pathways, reduced intracellular calcium mobilization and the activation-associated oxidant signal, and impaired mitochondrial function. When the ITC mixture was added shortly after activation, aggregometry signals consistent with destabilization of early platelet aggregates were observed whereas granule secretion was irreversible once initiated. In vivo , ITC mixture administration before or after the carrageenan challenge reduced thrombus formation and tissue injury, prolonged bleeding times, and reduced tail-necrosis length to a similar extent as the heparin reference group in this model. These findings identify the ITC mixture as a modulator of platelet signaling and metabolism, provide mechanistic insight into ITC-mediated antithrombotic effects, and support further evaluation of ITC-based interventions in thrombotic disease.
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BibTeX
@article{buchholz2026defined,
title = {{A defined isothiocyanate mixture suppresses platelet signaling and metabolism to limit thrombosis in vivo}},
author = {Jan Yağız Buchholz and Maria Shoykhet and Anthea C. Darius and Tobias Weiser and Erika Lynn Roberts and Mohammad Khosravi and Julie Petry and Seyedeh Zahra Mousavi and Babak Mohammadian and Lina Adams and Khouloud Hachani and Carola Eberhagen and Omid Azimzadeh and Hans Zischka and Gabriele Multhoff and Ali Bashiri Dezfouli and Barbara Wollenberg},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1944710},
url = {https://europepmc.org/article/PMC/PMC13661427},
note = {CC BY},
}
RIS
TY - JOUR
TI - A defined isothiocyanate mixture suppresses platelet signaling and metabolism to limit thrombosis in vivo
AU - Jan Yağız Buchholz
AU - Maria Shoykhet
AU - Anthea C. Darius
AU - Tobias Weiser
AU - Erika Lynn Roberts
AU - Mohammad Khosravi
AU - Julie Petry
AU - Seyedeh Zahra Mousavi
AU - Babak Mohammadian
AU - Lina Adams
AU - Khouloud Hachani
AU - Carola Eberhagen
AU - Omid Azimzadeh
AU - Hans Zischka
AU - Gabriele Multhoff
AU - Ali Bashiri Dezfouli
AU - Barbara Wollenberg
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1944710
UR - https://europepmc.org/article/PMC/PMC13661427
AB - Pathological platelet activation drives thrombosis and is a major contributor to morbidity and mortality. Current antiplatelet therapies reduce thrombotic risk but target a limited range of signaling pathways, have minimal impact on established platelet aggregates, and are frequently associated with bleeding complications. These drawbacks have prompted interest in alternative antiplatelet strategies. Isothiocyanates (ITCs), phytochemicals from cruciferous plants, have been reported to inhibit platelet function; however, their mechanisms and translational relevance remain incompletely defined. The effects of a defined mixture of allyl-, benzyl-, and phenethyl-isothiocyanate on platelet function were evaluated using ex vivo human platelets and an in vivo murine model of carrageenan-induced thrombosis. Platelet aggregation, intracellular signaling, calcium mobilization, redox balance, and mitochondrial function were assessed using functional assays, kinome profiling, flow cytometry, respirometry, and electron microscopy. The ITC mixture was administered before or after the carrageenan challenge. The ITC mixture inhibited platelet activation and aggregation induced by multiple agonists. It reduced peptide phosphorylation across multiple platelet signaling pathways, reduced intracellular calcium mobilization and the activation-associated oxidant signal, and impaired mitochondrial function. When the ITC mixture was added shortly after activation, aggregometry signals consistent with destabilization of early platelet aggregates were observed whereas granule secretion was irreversible once initiated. In vivo , ITC mixture administration before or after the carrageenan challenge reduced thrombus formation and tissue injury, prolonged bleeding times, and reduced tail-necrosis length to a similar extent as the heparin reference group in this model. These findings identify the ITC mixture as a modulator of platelet signaling and metabolism, provide mechanistic insight into ITC-mediated antithrombotic effects, and support further evaluation of ITC-based interventions in thrombotic disease.
SN - 1664-3224
ER -