American Society of Hirudotherapy

Bioactive Science

Molecular pharmacology of the medicinal leech salivary system

Last Updated: May 26, 2026Reviewed by: Andrei Dokukin, MD
Biology, biochemistry, mechanism — not clinical evidenceMechanism does NOT establish clinical efficacy outside FDA-cleared contexts

For molecular profiles of 201 characterized leech-derived compounds (with explicit drug-vs-leech distinction and clinical-translation-limit statements), see the Compound Reference. The Cycle 05 audit identified that every science / pharmacology / mechanistic-research page must clearly distinguish mechanism from clinical indication — this is now systemically enforced.

What does the science actually cover? Out of 440+ catalogued salivary proteins, only a small fraction has clinical evidence. See the Coverage Map for what is and isn't studied per organ system, and the Research Roadmap for how ASH is filling the gaps.

The medicinal leech salivary gland secretion (SGS) contains over 440 identified protein sequences — expanded from the 434 reported by Liu et al. (2019) with novel compounds identified in 2025 including a new cysteine-rich anticoagulant (Manuvera et al., 2025), three novel antimicrobial peptides (Serebrennikova et al., 2025), and the antimicrobial peptide hirunipin-2 (2025). These are organized into functional groups targeting anticoagulation, anti-inflammation, antimicrobial defense, and tissue remodeling. This section presents the molecular science underlying hirudotherapy — biological mechanisms, not therapeutic claims.

Educational Context

Discussion of biological mechanisms does not imply therapeutic efficacy outside FDA-cleared contexts. The science presented here informs our understanding of how the leech salivary system works at the molecular level.

Science Topics

Salivary Gland Secretion

Detailed overview of the 440+ protein secretome — functional groups, discovery timeline, and research field including 2025 discoveries.

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Hemostasis & Coagulation

Multi-target anticoagulant system: hirudin, calin, destabilase, antistasin, and the complete hemostatic cascade.

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Proteinase Inhibitors

14 characterized inhibitors including eglins, bdellins, LDTI, and LCI — roles in inflammation and tissue protection.

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Atherosclerosis Mechanisms

Lipid metabolism, endothelial function, platelet aggregation, and leech-derived compounds targeting vascular pathology.

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Neurotrophic Effects

BDNF-related activity, immunomodulatory factors, and complement system interactions.

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Anti-Inflammatory Mechanisms

Cytokine modulation, complement inhibition, and multi-pathway anti-inflammatory effects.

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Mechanisms of Action

Three interconnected therapeutic pathways: local humoral, neuroreflexive, and systemic humoral.

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Key Numbers

440+

Proteins Identified

Liu et al., 2019; expanded by Manuvera et al., Serebrennikova et al., 2025

39

Conserved Ortholog Clusters

Shared across 3 Hirudo species

6

FDA-Approved Derivatives

Including 3 from leech biology

Related Resources

Leech Biology

Anatomy, taxonomy, species, and thorough biological reference.

Pharmacology

From leech SGS to FDA-approved pharmaceuticals.

Clinical Specialties

How these mechanisms translate to clinical applications.

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.

Bioactive Science — Leech Salivary Pharmacology | ASH