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Conditions
12Raynaud's Syndrome (Primary)
Tier CInvestigational use for primary Raynaud's phenomenon; mechanism via local vasodilation and rheologic improvement. No RCT evidence.
Livedo Reticularis
Tier CInvestigational use for primary livedo reticularis; very limited evidence. Secondary causes (lupus, APLAS) require rheumatology referral.
Insulin Injection Lipohypertrophy
Tier CInvestigational use to soften and remodel insulin injection-related lipohypertrophy nodules; very limited evidence.
Peyronie's Disease (Stable Phase)
Tier CInvestigational use for stable-phase Peyronie's disease; case-report-level evidence only. Standard treatments (verapamil, collagenase, surgery) remain first-line.
Ménière's Disease (Adjunctive)
Tier CInvestigational adjunctive use for Ménière's disease; very limited evidence. Standard management (diet, betahistine, intratympanic therapy) remains primary.
Peripheral Vertigo (BPPV-Refractory / Vestibular Neuritis Recovery)
Tier CInvestigational adjunct for peripheral vertigo persisting after Epley maneuvers or during prolonged vestibular neuritis recovery; anecdotal.
Tarsal Tunnel Syndrome
Tier CInvestigational use for posterior tibial nerve entrapment at the medial ankle; very limited case-report evidence.
Pubic Symphysis Dysfunction (Non-Pregnancy)
Tier CInvestigational use for non-pregnancy-related pubic symphysis dysfunction including athletic osteitis pubis; anecdotal evidence.
Cluster Headache (Episodic)
Tier CHighly investigational use for episodic cluster headache between attack cycles; very limited anecdotal data, not for active attacks.
Severe Inflammatory Acne Vulgaris
Tier CHighly investigational use for severe nodulocystic acne refractory to isotretinoin; very limited anecdotal evidence and significant scarring risk concerns.
Cutaneous Lichen Planus (Localized)
Tier CInvestigational use for localized cutaneous lichen planus refractory to topical corticosteroid; very limited case-report evidence.
Chronic Anal Fissure (>8 Weeks)
Tier CInvestigational adjunct for chronic anal fissure refractory to medical therapy; very limited case-report evidence; surgical sphincterotomy remains gold standard.
Compounds
52Hyaluronidase
Enzyme that degrades hyaluronic acid in extracellular matrix — 'spreading factor' enhancing diffusion of other SGS compounds.
Ixodegrin (leech homolog)
Platelet GP IIb/IIIa antagonist family member — RGD-motif containing.
Leech Kallikrein Inhibitor
Plasma kallikrein-kinin system modulator — anti-inflammatory pathway distinct from cyclooxygenase.
Leech Nitric Oxide Synthase Modulator
Modulates host NOS activity at bite site — contributes to vasodilation phase of feeding.
Leech Histamine-like Vasodilator
Histamine-receptor-acting compound — contributes to local vasodilation at feeding site.
Leech Acetylcholine
Cholinergic vasodilator contributing to feeding-site vascular dilation.
Leech Collagenase
ECM-degrading enzyme — facilitates spread of salivary compounds at the bite site.
Leech Apyrase
ADP-degrading enzyme — prevents platelet aggregation by hydrolyzing ADP at bite site.
Leech Tissue Factor Pathway Inhibitor
Inhibitor of tissue factor / Factor VIIa complex — blocks extrinsic coagulation pathway.
Leech Thrombomodulin-binding factor
Modulates the thrombin-thrombomodulin axis — implications for protein C pathway.
Leech VEGF Modulator
Vascular endothelial growth factor pathway modulator — angiogenic and wound-healing implications.
Leech PDGF Modulator
Platelet-derived growth factor pathway modulator — implications for wound-healing.
Leech Eicosanoid Modulator
Modulates prostaglandin and leukotriene cascades — anti-inflammatory pathway.
Bufrudin
Direct thrombin inhibitor from the Asian buffalo leech — hirudin homolog described in Hirudinaria manillensis secretome.
Haemadipsin
Anticoagulant peptide described in the terrestrial Asian leech Haemadipsa zeylanica.
Whitmanin
Direct thrombin inhibitor homolog cataloged in the Chinese medicinal leech Whitmania pigra secretome.
Piscicolin
Small direct thrombin inhibitor described in the fish leech Piscicola geometra secretome.
Macrobdellin
Anticoagulant peptide described in the North American medicinal leech Macrobdella decora.
Destabilase-2
Second isoform of destabilase — lysozyme / isopeptidase activity targeting cross-linked fibrin.
Hirudinase
Alternate fibrin-cleaving enzyme reported in Hirudo medicinalis salivary secretions.
Collagenolytic Fibrinolysin
Dual-function protease degrading both fibrin clot scaffolds and collagen extracellular matrix.
Leech Bradykinin Modulator
Salivary factor reported to modulate the bradykinin / kinin-kallikrein vasoactive cascade.
Leech Substance P Modulator
Salivary factor reported to modulate the substance P / neurokinin-1 nociceptive pathway.
Leech Granulin-A
Granulin-family peptide identified in Hirudo medicinalis — putative growth-factor / wound-healing analog (mechanistic only).
Buccalin-Like Peptide
Putative neuroactive signaling peptide identified in leech salivary tissue — named by analogy to mollusc buccalin; function speculative.
Leech Thrombin-Cleavable Peptide
Substrate-mimetic peptide segment identified in leech salivary transcriptome — putative thrombin substrate / competitive inhibitor variant.
Leech Hirudo Lectin
Carbohydrate-binding lectin reported in Hirudo medicinalis salivary glands — putative agglutinin / immune modulator.
Leech Saposin-Like Peptide
Saposin-like lipid-binding peptide identified in leech salivary transcriptome — putative membrane-active component.
Leech Thrombospondin-Like Protein
Thrombospondin-type repeat (TSR)-domain protein identified in leech salivary transcriptome — putative platelet / matrix interactor.
Leech Phospholipase A2 Inhibitor
Putative PLA2 inhibitor identified in leech salivary transcriptome — candidate eicosanoid-cascade modulator.
Leech C-Type Lectin
C-type lectin domain protein identified in Hirudo medicinalis salivary transcriptome — putative carbohydrate / glycoprotein binder.
WP-Anticoagulant Genes (7-Transcript Family)
Whitmania pigra salivary anticoagulant gene family (Huang 2026 transcriptome) — seven coagulation-related transcripts including fibrinolytic enzymes, neutrophil-elastase inhibitors, factor Xa inhibitors.
Hirudin-Like Factors (HLFs)
Hirudin-paralog family lacking some structural hirudin features — Müller 2016 phylogenetic characterization across Hirudo and Hirudinaria genera.
Haemadipsa yanyuanensis Progranulin (Hy-PGRN)
Putative progranulin gene with 122 cysteine residues and nine tandem repeats — distinctive structural organization (Lin 2025 chromosome-level genome).
Haemadipsa yanyuanensis Bdellin Expansion
Lineage-specific 8.7-25-fold expansion of bdellin protease-inhibitor gene family in H. yanyuanensis genome (Lin 2025) — candidate driver of terrestrial-blood-feeding adaptation.
Haemadipsa yanyuanensis LDTI Expansion
Lineage-specific expansion of LDTI (leech-derived tryptase inhibitor) gene family in H. yanyuanensis (Lin 2025) — candidate mast-cell modulator repertoire.
Hirudinaria manillensis Macins (Hman1/Hman2/Hman3)
Three macin antimicrobial peptide paralogs from Asian buffalo leech — Yu 2025 documents Hman1 functional, Hman2 / Hman3 partly pseudogenized.
Hirudinaria bpling Anticoagulant Family
Chromosome-level genome of H. bpling (Khan 2025) annotates 20+ anticoagulant gene families including 'Bplins' — a novel species-specific factor family.
Hni-Antistasin
Novel anticoagulant factor identified in the Hirudo nipponia salivary-gland transcriptome — Kim 2024 de novo assembly + in situ hybridisation.
Hni-Ghilanten
Novel ghilanten family anticoagulant in the Hirudo nipponia salivary-gland transcriptome — Kim 2024 spatial expression mapping.
Hni-Bdellin
Novel bdellin family Kazal-domain trypsin / plasmin inhibitor identified in the Hirudo nipponia salivary-gland transcriptome — Kim 2024.
Hni-GLIPR1
Previously unrecognized immune-related glioma-pathogenesis-related protein 1 homolog in the Hirudo nipponia salivary gland — Kim 2024.
H. nipponia Starvation-Induced Salivary Proteome
181 differentially expressed proteins (72 up / 109 down) in starved Hirudo nipponia salivary glands — Cai 2024 proteomic + transcriptomic profiling.
H. yanyuanensis Bdellin Family Expansion (2025)
8.7–25× lineage-specific expansion of the bdellin gene family in the terrestrial blood-feeding leech Haemadipsa yanyuanensis — Lin 2025 chromosome-level genome.
H. yanyuanensis LCI Family Expansion (2025)
Lineage-specific expansion of the leech carboxypeptidase inhibitor (LCI) family in the terrestrial blood-feeding leech Haemadipsa yanyuanensis — Lin 2025.
H. yanyuanensis Progranulin (122-Cys Variant)
Distinctive progranulin paralog with 122 cysteine residues + nine tandem repeats in the terrestrial blood-feeding leech Haemadipsa yanyuanensis — Lin 2025.
H. verbana ERGA Chromosome-Level Anticoagulant Repertoire
First chromosome-level Hirudo verbana genome (14 pseudomolecules, 0.18 Gb, ERGA-BGE 2026) framing the southern medicinal leech as a primary genomic reference.
W. pigra Chromosome-Level Genome (79 Antithrombotic Genes)
Chromosome-level W. pigra genome unexpectedly carries 79 antithrombotic genes — more than the 72 in blood-sucking H. manillensis (Liu 2024).
Bloodsucking Leech FBN1 / GLB3 Expansion (Comparative)
Expanded FBN1 (fibrillin-1) + GLB3 (globin-3) gene families across H. nipponia / H. manillensis vs W. pigra — Zheng 2023 functional-genomic comparison.
Eglin C CTRL-Resistance Determinants
Structural determinants (Gln192, Lys218) explaining why eglin C, a classical broad-spectrum chymotrypsin / elastase inhibitor, poorly inhibits human chymotrypsin-like protease — Németh 2024.
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