A network pharmacology-based study on the mechanism of hirudin attenuates renal interstitial fibrosis through Nrf2 and NF-κB signalling pathways

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.

Resumen tomado de PubMed (NCBI) para el registro citado, en el idioma original. La versión de referencia es la de la publicación original.

El resumen se deja sin traducir para conservar la redacción original de los autores.

Using network pharmacology, molecular docking and in vitro validation in TGF-β1-stimulated HK-2 cells, hirudin reduced fibronectin and collagen I and modulated Nrf2 and NF-κB signalling, suggesting antifibrotic effects in renal interstitial fibrosis.

Explore cómo esta investigación se conecta con la práctica clínica

Más estudios revisados por pares en la categoría «Seguridad y control de infecciones».

• 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)
• Efficacy and Safety of Hirudotherapy for Improving Sperm Quality Parameters in Male Infertility: A Randomized Controlled Trial — Abtahi-Forooshani M et al. (2026)
• Improvement of patient care through hirudotherapy and the management of leeches from their reception to their disposal in France — Vaesken C et al. (2023)
• Hirudotherapy in Medicine and Dentistry — Jha K et al. (2015)
• Management of Chronic Non-healing Wounds by Hirudotherapy — Iqbal A et al. (2017)
• La hirudoterapia atenúa el dolor artrítico en pacientes con diversos síndromes de dolor crónico: un análisis retrospectivo — Loeser J et al. (2020)
• Hirudotherapy (medicinal leeches) for treatment of upper airway obstruction in a dog — Trenholme H, Masseau I, Reinero C (2021)
• Análisis de infecciones resistentes a antibióticos asociadas a la hirudoterapia — Brauer P et al. (2024)
• ¡Déjame en paz, sanguijuela! Hemartrosis atraumática tras hirudoterapia — Curcio J, Lloyd C (2020)

Ver toda la investigación analizada por la ASH →