American Society of Hirudotherapy

The Salivary Gland Complex

434+ identified proteins across anticoagulant, anti-inflammatory, and antimicrobial functional groups

Last Updated: March 5, 2026Reviewed by: Andrei Dokukin, MD

Last updated: March 14, 2026

The medicinal leech salivary system consists of paired salivary glands with unicellular secretory cells distributed along each jaw. This is the most extensively studied invertebrate secretome, containing a complex arsenal of bioactive molecules.

Discovery timeline

YearMilestoneSignificance
1884Haycraft identifies anticoagulant activity in leech extractFirst evidence of salivary bioactivity
1955Markwardt isolates and purifies hirudinFirst characterized salivary compound
1984Dodt et al. sequence the hirudin geneEnabled recombinant production
1990sAdditional compounds identified (calin, saratin, destabilase, eglin c)Revealed multi-target pharmacology
2020Kvist et al. — comprehensive transcriptomic/proteomic analysis434+ proteins identified across 3 Hirudo species

Scale of Discovery

Liu et al. (2019, Journal of Proteomics) identified 434+ full-length protein sequences in leech SGS using LC-MS/MS proteomic analysis. Complementing this, Kvist et al. (2020, Scientific Reports) used combined transcriptomic and proteomic approaches to characterize the salivary secretome. Of these, 39 orthologous clusters are shared across the three primary Hirudo species (H. medicinalis, H. verbana, H. orientalis), suggesting core functional conservation despite millions of years of divergent evolution.

The study employed RNA-seq of salivary gland tissue combined with mass spectrometry (LC-MS/MS) of secreted proteins, providing both transcript-level and protein-level confirmation. This dual-evidence approach increases confidence in the identified secretome.

Functional Groups

CompoundFunctionTargetMW
HirudinDirect thrombin inhibitorThrombin active site + exosite I~7 kDa
CalinPlatelet adhesion inhibitorCollagen/vWF binding~65 kDa
ApyraseADP hydrolysisADP-dependent platelet aggregation~45 kDa
DestabilaseFibrinolysis + antimicrobialε(γ-Glu)-Lys bonds, peptidoglycan~12 kDa
HyaluronidaseTissue penetrationHyaluronic acid in ECM~28.5 kDa
Eglin cProtease inhibitorElastase, cathepsin G, chymase~8 kDa
Bdellins A/BProtease inhibitorsTrypsin, plasmin, acrosin~6-7 kDa
SaratinAnti-adhesionPlatelet-collagen adhesion~12 kDa
AcetylcholineVasodilationMuscarinic receptors146 Da
Histamine-likeVasodilation + itchH1/H2 receptors~111 Da

Cross-species comparison

The three primary medicinal leech species share a conserved core secretome but also express species-specific variants. H. verbana, the most commonly used species in U.S. clinical practice, shows the highest expression levels for hirudin and destabilase. H. medicinalis produces a broader range of protease inhibitor variants. H. orientalis, used primarily in Eastern European and Asian practice, has a distinct profile of antimicrobial peptides.

These differences have practical implications: the choice of species may influence the pharmacological profile delivered during therapy, though clinical significance remains an open research question.

Functional Groups — Deep Dive

Regulatory Disclaimer

Mechanism discussion ≠ efficacy claims. Biological properties do not imply therapeutic benefit outside FDA-cleared contexts.

Related Resources

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.