Multi-target anticoagulant regulation by peptides from medicinal leeches: a unique natural strategy
Review published in Pharm Res (2025)
Abstract
BACKGROUND: Thrombotic diseases remain a major global health burden. Current anticoagulants are often limited by bleeding risks and narrow therapeutic windows, largely due to their single-target mechanisms. In contrast, medicinal leeches secrete diverse peptides that naturally and synergistically modulate multiple steps of the hemostatic system. METHODS: This paper systematically reviews published biochemical, structural, functional, and omics studies on leech-derived anticoagulant peptides, classifying them according to their molecular targets and antithrombotic mechanisms. RESULTS: Leech-derived peptides act synergistically at multiple key points of the coagulation cascade: (1) they inhibit platelet adhesion and aggregation by blocking the vWF-collagen interaction or suppressing GPIIb/IIIa; (2) they directly inhibit core coagulation proteases, such as thrombin and factor Xa; and (3) they interfere with fibrin stabilization and promote its dissolution by inhibiting factor XIIIa or modulating the fibrinolytic and intrinsic protease systems. From a molecular perspective, multispecies omics analyses have revealed a significant expansion of antithrombotic gene families and identified numerous novel peptide candidate genes. CONCLUSIONS: Leech-derived peptides provide a unique natural platform for multi-target anticoagulation and represent promising leads for next-generation antithrombotic agents. Combining traditional purification with genomics-guided discovery will accelerate mechanism elucidation, structural optimization, and translational development.
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Resumen
Review of multi-target anticoagulant regulation by leech-derived peptides as a unique natural strategy with drug-development implications.
Por qué esto importa para la hirudoterapia
This review systematically examines published biochemical, structural, functional, and omics studies on anticoagulant peptides derived from medicinal leeches, classifying them by molecular target and antithrombotic mechanism. The authors describe how these peptides act synergistically at multiple points—including platelet adhesion/aggregation inhibition, direct protease inhibition (thrombin, factor Xa), and interference with fibrin stabilization—proposing them as promising leads for next-generation antithrombotic agents. This is directly relevant to ASH's domain, as it synthesizes the molecular basis underlying the leech secretome's anticoagulant properties and highlights genomics-guided discovery of novel peptide candidates. As a review of existing literature, it provides no new primary experimental or clinical data, and the described peptides are characterized as leads rather than clinically validated therapies.
Citación
Multi-target anticoagulant regulation by peptides from medicinal leeches: a unique natural strategy.
Shi et al. · Pharmaceutical research, 2025
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026