American Society of Hirudotherapy

Inhibition of coagulation activation and inflammation by a novel Factor Xa inhibitor synthesized from the earthworm Eisenia andrei

Comparative biochemistry published in Biological & Pharmaceutical Bulletin (2009)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportDrug DevelopmentSalivary PharmacologyJoo SS et al. · Biological & pharmaceutical bulletin, 2009

Abstract

We have cloned an earthworm-derived Factor Xa (FXa) inhibitor, with an excellent inhibitory specificity from the midgut of the Eisenia andrei. We designate this inhibitor eisenstasin. An eisenstasin-derived small peptide (ESP) was synthesized and we examined whether ESP played an essential role in FXa inhibition. Compared to antistasin-derived small peptides (ASP) originating from leech, ESP primarily exhibited a high level of FXa inhibition in chromogenic peptide substrate assays and revealed an approximately 2-fold greater inhibition of FXa cleavage of a target protein than ASP. This suggests that ESP could be an effective anti-coagulant that targets FXa during the propagation step of coagulation. ESP also inhibited proteinase-activated receptor 2-mediated FXa activation, which may trigger endothelial inflammation. Endothelial nitric oxide (NO) was significantly reduced by ESP (p<0.0001), indicating that protease-activated receptor-2 (PAR-2) was effectively inactivated. We also found that ESP reduced the expressions of pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-8, IL-16, MCP-1, MIP-1alpha and MIP-1beta) by cultured cells treated with both ESP and FXa. Our results provide the first evidence that ESP might interrupt coagulation cascades by inhibiting FXa, and thereby may effectively control the bidirectional alternation between coagulation and inflammation.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsAnimalsAnti-Inflammatory Agents, Non-SteroidalAnticoagulantsAntineoplastic AgentsBlotting, WesternCell LineCytokinesDrug Screening Assays, AntitumorExtracellular Signal-Regulated MAP KinasesFactor XaFactor Xa InhibitorsHumans

Summary

Earthworm-derived Factor Xa inhibitor mirrors leech antistasin-type pharmacology — comparative annelid-derived antithrombotic research relevant to ASH catalog.

Why This Matters for Hirudotherapy

This study cloned a Factor Xa (FXa) inhibitor called eisenstasin from the earthworm Eisenia andrei and synthesized a derived small peptide (ESP). ESP showed higher FXa inhibition than leech-derived antistasin small peptides (ASP) in chromogenic substrate assays and greater inhibition of FXa cleavage of a target protein. ESP also inhibited PAR-2-mediated FXa activation, reduced endothelial nitric oxide (p<0.0001), and reduced expression of multiple pro-inflammatory cytokines in cell culture. This work is relevant to ASH's domain as a direct comparison with leech-derived antistasin peptides, situating earthworm-derived inhibitors within the same anticoagulant peptide class. However, the study is in vitro and involves no leeches or leech-derived material beyond the ASP comparator.

Citation

Inhibition of coagulation activation and inflammation by a novel Factor Xa inhibitor synthesized from the earthworm Eisenia andrei.

Joo SS et al. · Biological & pharmaceutical bulletin, 2009

DOI

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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