2026-10-12T00:42:16Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34029624 2026-09-30T04:45:37Z category_696 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_A defined isothiocyanate mixture suppresses platelet signaling and metabolism to limit thrombosis in vivo.docx Jan Yağız Buchholz (25141434) Maria Shoykhet (14435952) Anthea C. Darius (25141437) Tobias Weiser (21231776) Erika Lynn Roberts (25141440) Mohammad Khosravi (9109646) Julie Petry (21231779) Seyedeh Zahra Mousavi (13214017) Babak Mohammadian (25141443) Lina Adams (25141446) Khouloud Hachani (21231782) Carola Eberhagen (1998151) Omid Azimzadeh (193552) Hans Zischka (26601) Gabriele Multhoff (78405) Ali Bashiri Dezfouli (17800277) Barbara Wollenberg (233299) Genetic Immunology antithrombotic therapy isothiocyanates (ITCs) mitochondrial dysfunction oxidative stress platelet activation platelet aggregation <p>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.</p> 2026-09-30T04:45:37Z Dataset Dataset 10.3389/fimmu.2026.1944710.s001 https://figshare.com/articles/dataset/Supplementary_file_1_A_defined_isothiocyanate_mixture_suppresses_platelet_signaling_and_metabolism_to_limit_thrombosis_in_vivo_docx/34029624 CC BY 4.0