Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke
Basic science / preclinical published in Cell Mol Life Sci (2022)
Abstract
Ischemic stroke is a leading cause of death and disability worldwide. Increasing evidence indicates that ischemic stroke is a thromboinflammatory disease in which the contact-kinin pathway has a central role by activating pro-coagulant and pro-inflammatory processes. The blocking of distinct members of the contact-kinin pathway is a promising strategy to control ischemic stroke. Here, a plasma kallikrein and active FXII (FXIIa) inhibitor (sylvestin, contained 43 amino acids, with a molecular weight of 4790.4 Da) was first identified from forest leeches (Haemadipsa sylvestris). Testing revealed that sylvestin prolonged activated partial thromboplastin time without affecting prothrombin time. Thromboelastography and clot retraction assays further showed that it extended clotting time in whole blood and inhibited clot retraction in platelet-rich plasma. In addition, sylvestin prevented thrombosis in vivo in FeCl3-induced arterial and carrageenan-induced tail thrombosis models. The potential role of sylvestin in ischemic stroke was evaluated by transient and permanent middle cerebral artery occlusion models. Sylvestin administration profoundly protected mice from ischemic stroke by counteracting intracerebral thrombosis and inflammation. Importantly, sylvestin showed no signs of bleeding tendency. The present study identifies sylvestin is a promising contact-kinin pathway inhibitor that can proffer profound protection from ischemic stroke without increased risk of bleeding.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Identification of sylvestin, a 43-aa contact-kinin inhibitor from forest leeches Haemadipsa sylvestris. Inhibits plasma kallikrein and FXIIa, prolongs APTT, reduces thrombosis in FeCl/carrageenan models, and protects against ischemic stroke without bleeding tendency.
Por qué esto importa para la hirudoterapia
Este estudio identificó la silvestina, un inhibidor de la calicreína plasmática y del FXIIa de 43 aminoácidos (4.790,4 Da) procedente de sanguijuelas de bosque (Haemadipsa sylvestris), como un nuevo inhibidor de la vía de contacto-cininas. La silvestina prolongó el aPTT sin afectar el TP, extendió el tiempo de coagulación en sangre total, inhibió la retracción del coágulo, previno la trombosis en modelos arteriales inducidos por FeCl3 y modelos de cola inducidos por carragenina, y protegió profundamente a los ratones del accidente cerebrovascular isquémico en modelos de MCAO transitorio y permanente, sin tendencia hemorrágica. Para el ámbito de ASH, esto es directamente relevante: la silvestina es una nueva molécula antitrombótica/anti-tromboinflamatoria aislada de una especie de sanguijuela, lo que amplía el repertorio farmacológico de compuestos derivados de la sanguijuela. Caveat: se trata de un estudio preclínico (modelos en ratón); no se presentan datos en humanos, formulación ni ensayos clínicos; el resumen no reporta signos hemorrágicos en modelos animales, pero la seguridad y eficacia en humanos aún no están establecidas.
Citación
Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke.
Zhang Z et al. · Cellular and molecular life sciences, 2022
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026