Substanzreferenz

The most potent natural thrombin inhibitor — and the molecular template for three FDA-approved direct thrombin inhibitor drugs.

→ Lepirudin (Refludan)

Factor Xa inhibitor — prototype molecule that inspired the entire DOAC drug class (rivaroxaban, apixaban).

→ Conceptual ancestor: rivaroxaban (Xarelto)

Factor Xa inhibitor with anti-metastatic activity in animal cancer models — translational dual-use compound.

Factor Xa inhibitor with anti-inflammatory properties.

Hirudin variant from Hirudinaria manillensis with distinct kinetics.

Synthetic hirudin variant with improved oral pharmacokinetics — preclinical anticoagulant.

Synthetic 20-amino-acid hirudin analog — FDA-approved direct thrombin inhibitor for PCI anticoagulation ($636M peak revenue).

→ Angiomax / Angiox (FDA approved Dec 2000)

First-generation recombinant hirudin — FDA-approved 1998 for heparin-induced thrombocytopenia (HIT). Withdrawn 2012 by Bayer for commercial reasons.

→ Refludan (FDA approved 1998

Recombinant hirudin variant — FDA-approved 2003 for prophylaxis of DVT after hip replacement surgery.

→ Iprivask / Revasc (FDA approved April 2003)

Oral direct thrombin inhibitor — FDA approved 2010 for stroke prevention in atrial fibrillation. Conceptual descendant of hirudin pharmacology.

→ Pradaxa (FDA approved Oct 2010)

Synthetic small-molecule direct thrombin inhibitor — FDA approved 2000 for HIT and PCI. Designed using hirudin structural insights.

→ Argatroban (FDA approved 2000)

Oral Factor Xa inhibitor — FDA approved 2011. Conceptual descendant of antistasin/leech FXa research.

→ Xarelto (FDA approved July 2011)

Oral Factor Xa inhibitor — FDA approved 2012. Part of the DOAC class inspired by leech antistasin discovery.

→ Eliquis (FDA approved Dec 2012)

Oral Factor Xa inhibitor — FDA approved 2015. Latest of the antistasin-inspired DOAC class.

→ Savaysa / Lixiana (FDA approved Jan 2015)

Leech-derived inhibitor that potentiates host antithrombin III activity — synergistic anticoagulation.

Factor Xa inhibitor from Theromyzon tessulatum — Kunitz-domain analog with novel selectivity profile.

Picomolar-affinity thrombin inhibitor from Indian buffalo leech — distinct mechanism from hirudin.

Factor XIIIa inhibitor — blocks fibrin cross-linking; novel mechanism distinct from hirudin.

Inhibitor of tissue factor / Factor VIIa complex — blocks extrinsic coagulation pathway.

Modulates the thrombin-thrombomodulin axis — implications for protein C pathway.

Direct thrombin inhibitor from the Asian buffalo leech — hirudin homolog described in Hirudinaria manillensis secretome.

Anticoagulant peptide described in the terrestrial Asian leech Haemadipsa zeylanica.

Direct thrombin inhibitor homolog cataloged in the Chinese medicinal leech Whitmania pigra secretome.

Small direct thrombin inhibitor described in the fish leech Piscicola geometra secretome.

Anticoagulant peptide described in the North American medicinal leech Macrobdella decora.

Non-hirudin thrombin inhibitor from the rhynchobdellid leech Theromyzon tessulatum — highest-affinity natural inhibitor identified in a non-Hirudo species.

Small thrombin-inhibitor peptide identified in the Hirudo medicinalis salivary transcriptome — truncated hirudin-family analog.

Salivary protein family from Asian medicinal leeches Hirudo nipponia and Hirudo japonica — putative anticoagulant.

Substrate-mimetic peptide segment identified in leech salivary transcriptome — putative thrombin substrate / competitive inhibitor variant.

Novel cysteine-rich recombinant anticoagulant from Hirudo medicinalis saliva — strong anticoagulant activity in clotting assays; C-terminal motif governs membrane affinity.

Putative hirudin-like factor with RGD motif from African medicinal leech — dual thrombin-inhibitor / integrin-binder mechanism unique to A. fenestrata.

43-amino-acid contact-kinin pathway inhibitor from forest leech Haemadipsa sylvestris — plasma kallikrein + FXIIa dual blocker; preclinical stroke neuroprotection without bleeding tendency.

Thrombin exosite-II-binding 12-residue anticoagulant peptide screened from Whitmania pigra hydrolysates (Hua 2025) via computation-guided strategy.

Five-residue intestinally absorbable anticoagulant peptide from Whitmania pigra trypsin hydrolysate — Fang 2025 peptidomics + everted-gut-sac validation.

Whitmania pigra-derived anticoagulant peptide showing neuroprotection in rat MCAO ischemia-reperfusion model (Liu 2026) — thrombin modulation + fibrinolysis homeostasis.

Bivalent exosite-II thrombin inhibitor from the Malayan land leech Haemadipsa interrupta — Müller 2024 transcriptome identification + recombinant functional characterization.

Whitmania pigra salivary anticoagulant gene family (Huang 2026 transcriptome) — seven coagulation-related transcripts including fibrinolytic enzymes, neutrophil-elastase inhibitors, factor Xa inhibitors.

Tyrosine-sulfated, O-glycosylated hirudin variant from Hirudo medicinalis — Maxwell 2023 chemical-synthesis study reveals sulfation increases thrombin inhibition ~10-fold.

Hirudin-paralog family lacking some structural hirudin features — Müller 2016 phylogenetic characterization across Hirudo and Hirudinaria genera.

Multi-domain hirudin superfamily proteins from H. tianjinensis (Kalatehjari 2026) — two-or-more central globular domains per molecule.

Salivary-gland hirudin variant from H. nipponia (Shi 2023) — recombinant Pichia pastoris expression with documented antithrombin activity (14,000 ATU/mL).

First documented hirudin / hirudin-like factor family in a non-hematophagous leech — Müller 2022 thrombin-inhibitory characterization of W. pigra salivary transcripts.

Non-classical Kazal-type protease inhibitor from Hirudinaria manillensis — prolongs aPTT without inhibiting trypsin, thrombin, FXa, FXIIa, or kallikrein (Cheng 2019).

Bivalent tandem-domain hirudin homolog from Hirudinaria manillensis — two globular domains without C-terminal tail; structurally distinct from kissing-bug / tick analogs (Lukas 2022).

Synthetic phosphotyrosine-63 hirudin analog with higher thrombin affinity than native sulfo-hirudin — Volkova 2023 steered-MD + in vitro plasma assay.

Novel Hirudo medicinalis salivary protein (28% identity to antistasin) with stronger aPTT inhibition than hirudin at equimolar concentration — Manuvera 2024.

11 hirudin / HLF paralogs from the North-African medicinal leech — Ahmed 2024 documents highest hirudin gene diversity within the genus Hirudo and three recombination-derived chimeras.

Four-domain antistasin-like recombinant anticoagulant from H. medicinalis (Brovina 2026) — inhibits intrinsic + extrinsic + common pathway via aPTT / PT / TT.

Three lefaxin paralogs in H. nipponia + W. pigra genomes (Ye 2025) — H. nipponia variants exhibit stronger FXa binding and in vitro anticoagulant activity than W. pigra.

20.8 kDa thermostable anticoagulant protein from Whitmania pigra decoction — active across 20-100°C and pH 2-8 (Zhang 2022).

Eleven-residue anticoagulant + thrombolytic peptide from Whitmania pigra alcalase hydrolysate — Ren 2016 documents activity in aPTT, PT, and TT assays with thrombolytic effect.

Chromosome-level genome of H. bpling (Khan 2025) annotates 20+ anticoagulant gene families including 'Bplins' — a novel species-specific factor family.

Putative hirudin variant from the salivary transcriptome of the African medicinal leech Asiaticobdella fenestrata — Schulz 2025 recombinant characterization in coagulation assays.

Novel anticoagulant factor identified in the Hirudo nipponia salivary-gland transcriptome — Kim 2024 de novo assembly + in situ hybridisation.

Novel ghilanten family anticoagulant in the Hirudo nipponia salivary-gland transcriptome — Kim 2024 spatial expression mapping.

Hirudo nipponia salivary-gland hirudin variant identified by transcriptome + in situ hybridisation — Kim 2024 and Shi 2023 (Pichia pastoris recombinant production, 14,000 ATU/mL).

Recombinant E. coli–expressed Hirudo medicinalis novel anticoagulant protein, 28 % antistasin-identical, exceeding hirudin in aPTT inhibition — Manuvera 2024.

First chromosome-level Hirudo verbana genome (14 pseudomolecules, 0.18 Gb, ERGA-BGE 2026) framing the southern medicinal leech as a primary genomic reference.

Three lefaxin genes in H. manillensis (Hman1/2/3) with stronger Factor Xa binding + anticoagulant activity than non-hematophagous comparators — Ye 2025.

First of five H. manillensis hirudin variants — Liu 2023 demonstrates anticoagulant activity (vs hirudin_Hman3/4 which were inactive).

Second active H. manillensis hirudin paralog — Liu 2023 genome annotation + recombinant activity confirmation.

Fifth-paralog active H. manillensis hirudin variant from the comprehensive genome annotation — Liu 2023.

Computation-guided 12-mer anticoagulant peptide from Whitmania pigra hydrolysate targeting thrombin Exosite II — Hua 2025 in vivo + SPR validation.

Chromosome-level W. pigra genome unexpectedly carries 79 antithrombotic genes — more than the 72 in blood-sucking H. manillensis (Liu 2024).

Hidden hirudin-like factor present in H. medicinalis, H. verbana and H. orientalis whose native form has low anticoagulant activity — Müller 2020.

Paralogous hidden hirudin-like factor in H. medicinalis / verbana / orientalis whose native form has minimal anticoagulant activity — Müller 2020 structure-activity engineering.

Thermostable (20–100 °C, pH 2–8) ~20.8 kDa anticoagulant protein from Whitmania pigra decoction — Zhang 2022 in vivo carrageenan thrombosis model.

Systematic review of hirudin novel drug delivery systems addressing the bioavailability + protease-degradation bottleneck — Mo 2024.

5-residue thrombin-binding anticoagulant peptide from Whitmania pigra hydrolysate — Liu 2024 docking + activity validation.

Early W. pigra anticoagulant cDNA clones with hementin-like / saratin-like activities, compiled by Tang 2020.

Anti-platelet adhesion protein that blocks von Willebrand factor–collagen binding.

Anti-platelet adhesion protein blocking collagen-mediated platelet activation.

RGD-containing peptide inhibiting platelet GP IIb/IIIa receptor — eptifibatide ancestor.

→ Conceptual ancestor: eptifibatide (Integrilin)

RGD-peptide GP IIb/IIIa antagonist — sister molecule to decorsin from a different leech species.

Cyclic heptapeptide GP IIb/IIIa receptor antagonist — FDA approved 1998. Structural inspiration: leech decorsin.

→ Integrilin (FDA approved May 1998)

Platelet GP IIb/IIIa antagonist family member — RGD-motif containing.

ADP-degrading enzyme — prevents platelet aggregation by hydrolyzing ADP at bite site.

Isoform of saratin — collagen-binding anti-platelet protein from Hirudo medicinalis.

Fibrinogenolytic / anti-platelet protein homologous to hementin — disrupts platelet aggregation.

Isoform of LAPP — collagen-binding inhibitor of platelet adhesion.

Salivary protein blocking platelet adhesion to extracellular matrix components.

Collagen-binding antiplatelet variant from the Hirudo medicinalis sialotranscriptome — paralog of saratin and saratin-2.

Antiplatelet peptide identified in leech salivary transcriptome — inhibits platelet aggregation in vitro.

Paralog of gelin identified in the Hirudo medicinalis sialotranscriptome — putative antiplatelet variant.

Antiplatelet protein from Haementeria officinalis — vWF-A1 / collagen-binding inhibitor with reported antithrombotic activity in preclinical models.

Secondary RGD-motif platelet-aggregation inhibitor reported from the leech salivary secretome — family member with decorsin / ornatin.

Thrombospondin-type repeat (TSR)-domain protein identified in leech salivary transcriptome — putative platelet / matrix interactor.

RGD-motif platelet aggregation inhibitor from the African medicinal leech Asiaticobdella fenestrata — N-terminal RGD distinguishes it from decorsin / ornatin paralogs.

Second RGD-motif platelet aggregation inhibitor paralog from Asiaticobdella fenestrata — Schulz 2025 sialotranscriptome.

First oligomeric decorsin-class platelet aggregation inhibitor identified in a haemadipsid leech (Müller 2024) — weak inhibitor in functional assays.

Monomeric + oligomeric decorsin paralogs identified in Asian medicinal leech H. tianjinensis (Kalatehjari 2026) — first recombinant characterization as platelet aggregation inhibitors.

One monomeric + four multimeric decorsin paralogs from Asian buffalo leech — Tolksdorf 2025 demonstrates platelet-aggregation inhibitory activity for all but one paralog.

Selective PAR1 antagonist from non-hematophagous Whitmania pigra — Ren 2019 demonstrates antithrombotic activity in rat without prolonging bleeding time.

30-residue antiplatelet peptide from Whitmania pigra selectively inhibiting thrombin-induced platelet aggregation — Liu 2016 demonstrates rat arterio-venous shunt thrombosis attenuation.

Putative N-terminal-RGD-motif platelet aggregation inhibitor from the African medicinal leech Asiaticobdella fenestrata — Schulz 2025 recombinant characterization.

Hirudo nipponia saratin homolog — Cheng 2023 cloning + recombinant production demonstrates collagen-binding antiplatelet activity.

One monomeric + four multimeric decorsin-encoding genes in the H. manillensis genome — Tolksdorf 2025 recombinant platelet-aggregation-inhibitory characterization.

Monomeric and oligomeric decorsins + hirudins + hirudin-like factors across H. nipponia and H. tianjinensis — Kalatehjari 2026 recombinant platelet-aggregation characterization.

First-described platelet-aggregation-inhibitor decorsin (Seymour 1990) from the North American leech Macrobdella decora — RGD-motif anchor for the leech antiplatelet superfamily.

Lysozyme with isopeptidase activity that dissolves stabilized fibrin clots — including aged thrombi resistant to tPA.

Direct fibrinogenolytic enzyme — degrades fibrinogen independently of plasmin.

Direct fibrinogenolytic enzyme cleaving fibrinogen alpha-chain at unique sites — independent of plasmin.

Isopeptidase domain of destabilase that cleaves cross-linked fibrin — distinct from lysozyme domain.

Second isoform of destabilase — lysozyme / isopeptidase activity targeting cross-linked fibrin.

Alternate fibrin-cleaving enzyme reported in Hirudo medicinalis salivary secretions.

Dual-function protease degrading both fibrin clot scaffolds and collagen extracellular matrix.

Paralog variant of destabilase identified in Hirudo medicinalis sialotranscriptome — isopeptidase/lysozyme bifunctional family member.

Whitmania pigra destabilase ortholog (Huang 2026) — isopeptidase + clot-destabilizing activity; C-terminal IPATETTTEI deletion enhances isopeptidase activity.

Hirudinaria manillensis destabilase / i-type lysozyme (Gao 2025) — isopeptidase + lysozyme activity, salivary-gland-upregulated on blood feeding.

Recombinant H. medicinalis destabilase tested against aged human blood clots resistant to thrombolytics — Bobrovsky 2021 demonstrates dose-response isopeptide-bond cleavage.

Serine proteinase inhibitor targeting tissue kallikrein — anti-inflammatory pathway.

Potent inhibitor of human leukocyte elastase and cathepsin G — anti-inflammatory protein widely used as research tool.

Kazal-type proteinase inhibitor targeting trypsin and plasmin — modulates inflammatory cascade.

Selective inhibitor of human mast cell tryptase — anti-inflammatory pathway.

Inhibitor of TAFI (thrombin-activatable fibrinolysis inhibitor) — synergizes with hirudin's anticoagulant action.

Selective elastase inhibitor from Korean leech — anti-inflammatory potential in COPD and emphysema research.

Plasma kallikrein and trypsin inhibitor from Korean leech — anti-inflammatory and antithrombotic research.

Trypsin and plasmin inhibitor; closely related to bdellins — anti-fibrinolytic modulation.

Plasma kallikrein-kinin system modulator — anti-inflammatory pathway distinct from cyclooxygenase.

Trypsin-plasmin inhibitor of Kazal-type family — sister to Bdellin B3.

Plasmin inhibitor of Kazal-type family — anti-fibrinolytic.

Trypsin and Factor Xa inhibitor with broad-spectrum serine protease activity.

Additional bdellin variant — Kazal-type proteinase inhibitor with trypsin/plasmin specificity.

Sequence variant of LDTI — selective tryptase / trypsin inhibitor relevant to mast-cell pathways.

Leech homolog of pancreatic (Kunitz-type) trypsin inhibitor — broad serine protease inhibition.

Salivary inhibitor of neutrophil elastase — modulates inflammatory tissue damage.

Paralog of LDTI identified in Hirudo medicinalis salivary transcriptome — Kazal-type mast-cell tryptase inhibitor variant.

Additional Kazal-domain serine protease inhibitor reported in the leech salivary transcriptome with mast-cell tryptase selectivity.

Bovine pancreatic trypsin inhibitor (Kunitz)-family homolog identified in Hirudo medicinalis sialotranscriptome — sister to LPTI / LCI.

Additional Kazal-family serine protease inhibitor cataloged in Hirudo medicinalis sialotranscriptome — broad serine-protease specificity.

Cystatin-family cysteine protease inhibitor identified in leech salivary transcriptome — inhibits cathepsin-like host enzymes.

Serpin-family protease inhibitor identified in Hirudo medicinalis salivary transcriptome — large suicide-substrate inhibitor variant.

TIMP / netrin-domain metalloprotease inhibitor variant in leech salivary transcriptome — putative MMP regulator at bite site.

Recombinant cystatin / cysteine protease inhibitor from Haementeria vizottoi leech — Linhares 2021 potent CatL inhibitor (Ki 7.9 nM).

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.

Lineage-specific expansion of LDTI (leech-derived tryptase inhibitor) gene family in H. yanyuanensis (Lin 2025) — candidate mast-cell modulator repertoire.

Comparative LDTI gene family analysis across 4 medicinal leech species (H. nipponia, H. manillensis, W. pigra, H. tianjinensis) — Xiao 2025 documents H. nipponia as optimal therapeutic candidate.

Antistasin-domain dual analgesic + antithrombotic serine protease inhibitor from Poecilobdella manillensis — Wang 2023 explains the painless-bleed phenotype.

48-aa antistasin-type single-domain serine protease inhibitor from Poecilobdella manillensis — anticoagulant + anti-ischemic-stroke preclinical activity (Tang 2018).

Novel bdellin family Kazal-domain trypsin / plasmin inhibitor identified in the Hirudo nipponia salivary-gland transcriptome — Kim 2024.

8.7–25× lineage-specific expansion of the bdellin gene family in the terrestrial blood-feeding leech Haemadipsa yanyuanensis — Lin 2025 chromosome-level genome.

Lineage-specific expansion of the leech carboxypeptidase inhibitor (LCI) family in the terrestrial blood-feeding leech Haemadipsa yanyuanensis — Lin 2025.

Structural determinants (Gln192, Lys218) explaining why eglin C, a classical broad-spectrum chymotrypsin / elastase inhibitor, poorly inhibits human chymotrypsin-like protease — Németh 2024.

Lineage-specific expansion of the leech-derived tryptase inhibitor (LDTI) family in Haemadipsa yanyuanensis terrestrial leech — Lin 2025.

Antimicrobial peptide active against Gram-negative bacteria — innate immunity of leech.

Antimicrobial peptide; structural analogue of mammalian defensin family.

Antimicrobial peptide active against Gram-positive bacteria — amphipathic alpha-helix.

Newly-characterized antimicrobial peptide family (Kumar 2025) — candidate next-generation antibiotics against AMR pathogens.

Lysozyme domain of destabilase — antimicrobial activity against peptidoglycan-containing bacteria.

Anti-Gram-positive peptide isolated from Asian medicinal leech salivary glands.

Isoform of theromycin — leech-derived antimicrobial / anti-inflammatory peptide.

Defensin-family cationic antimicrobial peptide identified in leech salivary tissue.

Cecropin-homolog antimicrobial peptide identified in the leech salivary secretome.

Macin-family broad-spectrum antimicrobial protein identified in leech immune tissue and salivary secretome.

Macin-family antimicrobial protein with reported neuronal-tissue specificity — leech innate immunity component.

Specific hirunipin variant (Kumar 2025) active against multi-drug-resistant Acinetobacter baumannii — biofilm eradication, antibiotic synergy, anti-inflammatory in macrophages.

Novel lumbricin-family antimicrobial peptide from Hirudo medicinalis (Serebrennikova 2025) — N-terminal fragment is unique among known AMPs; active against Bacillus subtilis.

Novel macin-family antimicrobial peptide from Hirudo medicinalis genome — Serebrennikova 2025 high-throughput screen.

Second macin-family antimicrobial peptide candidate from Hirudo medicinalis (Serebrennikova 2025) — paralog of NrlHM1.

Novel antimicrobial peptide from Hirudinaria manillensis salivary transcriptome — MIC 6.25 µg/mL against MRSA, no thrombogenic effect, in vivo efficacy in mice.

Three macin antimicrobial peptide paralogs from Asian buffalo leech — Yu 2025 documents Hman1 functional, Hman2 / Hman3 partly pseudogenized.

Conserved cysteine-stabilized αβ macin from the Asian buffalo leech — Yu 2025 demonstrates retained antimicrobial function while Hman2/Hman3 paralogs degenerate.

Recombinant heterologous-expression screening of candidate Hirudo medicinalis macin paralogs in E. coli — Serebrennikova 2025 (LBrHM1, NrlHM1, NrlHM2, lumbricin/macin families).

11-mer antimicrobial peptide RK22 from Hirudinaria manillensis salivary-gland transcriptome — Lu 2023 demonstrates MRSA killing + biofilm eradication.

Complement system modulator targeting C1q activation — immunological homeostasis.

Modulates prostaglandin and leukotriene cascades — anti-inflammatory pathway.

Putative PLA2 inhibitor identified in leech salivary transcriptome — candidate eicosanoid-cascade modulator.

Putative progranulin gene with 122 cysteine residues and nine tandem repeats — distinctive structural organization (Lin 2025 chromosome-level genome).

Whitmania pigra-derived 15-residue anti-atherosclerosis peptide — Hu 2020 demonstrates inhibition of macrophage migration via JNK + p38 MAPK pathways.

Modulates host NOS activity at bite site — contributes to vasodilation phase of feeding.

Histamine-receptor-acting compound — contributes to local vasodilation at feeding site.

Cholinergic vasodilator contributing to feeding-site vascular dilation.

Salivary factor reported to modulate the bradykinin / kinin-kallikrein vasoactive cascade.

Three angiogenic peptides (DSYVGDEAQSKR, YNELRVAPEEHP, IQFLPEGSPVTM) from a leech + earthworm Shuxuetong (SXT) injection — Sun 2022 hindlimb-ischemia model.

Enzyme that degrades hyaluronic acid in extracellular matrix — 'spreading factor' enhancing diffusion of other SGS compounds.

→ Conceptual relative: human recombinant hyaluronidase (Hylenex)

ECM-degrading enzyme — facilitates spread of salivary compounds at the bite site.

Hyperactive Hirudo medicinalis hyaluronate hydrolase used for HA oligosaccharide industrial production — Liao 2023 yeast-surface-display recombinant biocatalyst.

Salivary factor reported to modulate the substance P / neurokinin-1 nociceptive pathway.

Growth factor and wound-healing modulator — promotes angiogenesis and tissue regeneration.

Vascular endothelial growth factor pathway modulator — angiogenic and wound-healing implications.

Platelet-derived growth factor pathway modulator — implications for wound-healing.

Granulin-family peptide identified in Hirudo medicinalis — putative growth-factor / wound-healing analog (mechanistic only).

Putative neuroactive signaling peptide identified in leech salivary tissue — named by analogy to mollusc buccalin; function speculative.

Carbohydrate-binding lectin reported in Hirudo medicinalis salivary glands — putative agglutinin / immune modulator.

Saposin-like lipid-binding peptide identified in leech salivary transcriptome — putative membrane-active component.

C-type lectin domain protein identified in Hirudo medicinalis salivary transcriptome — putative carbohydrate / glycoprotein binder.

First D-leucine-containing linear peptides discovered in any leech — Zhang 2019 demonstrates neuroprotection in oxygen-glucose deprivation Neuro-2a model with high serum stability.

Previously unrecognized immune-related glioma-pathogenesis-related protein 1 homolog in the Hirudo nipponia salivary gland — Kim 2024.

181 differentially expressed proteins (72 up / 109 down) in starved Hirudo nipponia salivary glands — Cai 2024 proteomic + transcriptomic profiling.

Distinctive progranulin paralog with 122 cysteine residues + nine tandem repeats in the terrestrial blood-feeding leech Haemadipsa yanyuanensis — Lin 2025.

Preclinical demonstration that hirudin attenuates idiopathic-pulmonary-fibrosis fibroblast senescence via the PGC1α / Sirt3 axis — He 2024 mouse model + primary lung fibroblasts.

Molecular-weight-fractionated leech extract (>10 kDa) attenuates pulmonary fibrosis via TGFβ1 / Smad3 / PKM2 / Smad7 — Zhang 2024 bleomycin-induced mouse model.

Nano-liposomal medicinal leech saliva extract (46.23 nm) downregulates VEGFA + induces apoptosis in MCF-7 breast-cancer cells — Shakouri 2021.

Dorsal random skin-flap rat model: medicinal leech application + leech saliva extract injection both increase VEGF, neovascularisation + reduce necrosis vs control — Ünal 2025.

Expanded FBN1 (fibrillin-1) + GLB3 (globin-3) gene families across H. nipponia / H. manillensis vs W. pigra — Zheng 2023 functional-genomic comparison.

Comprehensive review of ~100 chemical constituents + bioactivities of Chinese medicinal leech (Shuizhi) — Liu 2025 covering anticoagulant, antithrombotic, antiatherosclerotic, anti-fibrotic, anti-inflammatory activities.

Mechanistic review of hirudin's anti-coagulant, anti-fibrotic, anti-thrombotic, anti-inflammatory effects in diabetic-nephropathy preclinical + clinical research — Tian 2024.

Review of leech extract's cardiovascular and atherosclerotic pharmacological effects in animal + cell models — May 2022.

Review of leech extract + saliva pharmacological mechanisms relevant to pulmonary fibrosis and other fibrotic diseases — Sarli 2019 (Iranian Group).

Review synthesising leech-extract anti-atherosclerotic pharmacological mechanisms across animal + cell models — Eldor 2019.

2024 reproteomic re-characterisation of medicinal-leech saliva extending the Babenko 2020 proteome — Polishchuk 2024.