Multi-Target Anticoagulant Regulation by Peptides from Medicinal Leeches: A Unique Natural Strategy against Thrombosis
Research article published in Pharmaceutical research (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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Multi-Target Anticoagulant Regulation by Peptides from Medicinal Leeches: A Unique Natural Strategy against Thrombosis.
Why This Matters for Hirudotherapy
This review systematically examines published biochemical, structural, functional, and omics studies on anticoagulant peptides derived from medicinal leeches, categorizing them by molecular targets and antithrombotic mechanisms. The abstract details how these peptides act synergistically at multiple points of the coagulation cascade, including inhibiting platelet adhesion and aggregation, directly targeting proteases such as thrombin and factor Xa, and interfering with fibrin stabilization and dissolution. This work is directly relevant to ASH's domain as it addresses the bioactive peptide components of medicinal leech secretions and their multi-target anticoagulant properties. However, the paper discusses leech-derived peptides as promising drug leads and discovery platforms rather than providing evidence regarding the clinical efficacy of hirudotherapy itself; as a review, it synthesizes existing literature without generating new experimental data.
Citation
Multi-Target Anticoagulant Regulation by Peptides from Medicinal Leeches: A Unique Natural Strategy against Thrombosis
Shi P et al. · Pharmaceutical research, 2025
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