A network pharmacology-based study on the mechanism of hirudin attenuates renal interstitial fibrosis through Nrf2 and NF-κB signalling pathways
Mechanism study published in Naunyn-Schmiedeberg's Archives of Pharmacology (2026)
Abstract
This study was aimed at elucidating the therapeutic effects of hirudin on renal interstitial fibrosis (RIF) and at delineating the molecular mechanisms underlying its antifibrotic actions. A comprehensive research approach was adopted, integrating network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experimental validation, to explore the mechanisms through which hirudin alleviates RIF. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 185 enriched signalling pathways, with the primary ones being the VEGF signalling pathway, TNFA signalling pathway and NF-κB signalling pathway. Gene Ontology (GO) analysis revealed that hirudin's antifibrotic effects were associated with inflammatory responses, canonical NF-κB signal transduction, and cellular responses to oxidative stress. Protein-protein interaction (PPI) network analysis identified TNF, HIF1A, HO-1, CASP3, IKBA, KEAP1, and RELA as key hub proteins. Experimental validation demonstrated that hirudin significantly reduced the protein levels of fibronectin (FN) and collagen I (Col I) in TGF-β1-stimulated HK-2 cells. Additionally, hirudin downregulated pro-inflammatory markers (TNF-α, MCP-1, p-P65, and p-IκBα) while upregulating antioxidant proteins (Nrf2, HO-1, and SOD-1). These findings suggest that hirudin mitigates TGF-β1-induced inflammation and oxidative stress in HK-2 cells by modulating the Nrf2 and NF-κB signalling pathways, thereby impeding the progression of RIF.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Network pharmacology and in vivo validation showing leech-derived hirudin attenuates renal interstitial fibrosis via Nrf2 and NF-κB signaling pathways — extends hirudin into nephrology.
Why This Matters for Hirudotherapy
This study used network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experiments to investigate how hirudin attenuates renal interstitial fibrosis (RIF) by modulating the Nrf2 and NF-κB signaling pathways. Hirudin reduced fibrosis markers (fibronectin, collagen I) and pro-inflammatory markers while upregulating antioxidant proteins in TGF-β1-stimulated HK-2 cells, suggesting it mitigates inflammation and oxidative stress. The abstract does not describe hirudin as leech-derived, nor does it reference traditional anticoagulant use or hirudotherapy, so the relevance to ASH is limited to the pharmacological study of a compound named hirudin. The main caveat is that findings are based on computational analysis and a cultured cell line, with no human or animal data.
Citation
A network pharmacology-based study on the mechanism of hirudin attenuates renal interstitial fibrosis through Nrf2 and NF-κB signalling pathways.
Yang K et al. · Naunyn-Schmiedeberg's archives of pharmacology, 2026
Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026