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.
Resumen
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.
Por qué esto importa para la hirudoterapia
Este estudio empleó farmacología de redes, acoplamiento molecular, simulaciones de dinámica molecular y experimentos in vitro para investigar cómo la hirudina atenúa la fibrosis intersticial renal (FIR) mediante la modulación de las vías de señalización Nrf2 y NF-κB. La hirudina redujo los marcadores de fibrosis (fibronectina, colágeno I) y los marcadores proinflamatorios, al mismo tiempo que reguló al alza las proteínas antioxidantes en células HK-2 estimuladas con TGF-β1, lo que sugiere que mitiga la inflamación y el estrés oxidativo. El resumen no describe la hirudina como derivada de sanguijuela, ni hace referencia al uso anticoagulante tradicional ni a la hirudoterapia, por lo que la relevancia para ASH se limita al estudio farmacológico de un compuesto denominado hirudina. La principal salvedad es que los hallazgos se basan en análisis computacional y en una línea celular cultivada, sin datos en humanos ni en animales.
Citación
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
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026