Synthetic anticoagulant octaparin targets mitochondrial cardiolipin-GSDMD axis to rescue redox homeostasis in sepsis

Sepsis, characterized by dysregulated immune responses and mitochondrial dysfunction, currently has few effective therapies that directly target these cellular mechanisms, and conventional heparin and related analogues provide inadequate immunomodulatory benefits. Here, we investigated the synthetic heparin analogue octaparin, which exhibits enhanced anticoagulant safety, for its potential to mitigate sepsis by targeting mitochondrial and redox pathways. Using murine models of lipopolysaccharide (LPS)-induced endotoxemia and Salmonella typhimurium-induced sepsis, along with in vitro studies performed using murine bone marrow-derived macrophages (BMDMs) and the human acute monocytic leukemia THP-1 cell line, we demonstrate that octaparin significantly improves survival and attenuates multi-organ (lung, liver, kidney) damage. Octaparin outperformed heparin, enoxaparin, and fondaparinux in suppressing systemic inflammation including TNF-α, IL-6, IL-1β and bacterial burden. Transcriptomic analysis revealed octaparin reprograms macrophage immunometabolism, suppressing pro-inflammatory pathways while enhancing phagocytosis. Crucially, octaparin inhibited both canonical and non-canonical inflammasome activation, reduced generation of the pyroptotic executor GSDMD-N-terminal fragment (GSDMD-NT), and specifically diminished mitochondrial localization of GSDMD-NT by downregulating key cardiolipin synthesis and transport genes. Furthermore, octaparin uniquely reversed LPS-induced mitochondrial dysfunction. This restoration was accompanied by improvements in mitochondrial quality and the reestablishment of redox homeostasis. Collectively, octaparin confers multifaceted protection in sepsis, positioning it as a promising redox-targeted therapeutic for sepsis.

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

Peer-reviewed research on safety and infection-control considerations relevant to leech therapy and anticoagulation. Indexed in PubMed and verified against the NCBI record.

Erfahren Sie, wie diese Forschung mit der klinischen Praxis verknüpft ist

More peer-reviewed studies in Sicherheit & Infektionskontrolle.

• Leech-Assisted Flap Salvage — Systematic Review of 277 Cases — Whitaker et al. (2012)
• Effects of hirudotherapy on liver functions, lipid profile, and insulin sensitivity in rats with metabolic syndrome — Bilden A et al. (2026)
• AIF-1 and RNASET2 Play Complementary Roles in the Innate Immune Response of Medicinal Leech — Baranzini N et al. (2019)
• [Hirudo medicinalis-leech applications in plastic and reconstructive microsurgery--a literature review] — Knobloch K et al. (2007)
• Bacterial symbioses of the medicinal leech Hirudo verbana — Nelson M, Graf J (2012)
• Leech related Aeromonas complex infection after reconstruction with a microvascular forearm flap — Beger B, von Loewenich F, Goetze E, Moergel M, Walter C (2016)
• Aeromonas septicemia after medicinal leech use following replantation of severed digits — Levine SM, Frangos SG, Hanna B, Colen K, Levine JP (2009)
• Outcomes of flap salvage with medicinal leech therapy — Nguyen MQ et al. (2012)
• The role of leech water sampling in choice of prophylactic antibiotics in medical leech therapy — Wilmer A et al. (2013)
• The development and application of mini-barcodes from mitochondrial DNA for identifying medicinal leeches from traditional medicines — Liu Y et al. (2025)

Browse all ASH-analysed research →