A novel integrated strategy for discovering absorbable anticoagulant bioactive peptides: a case study on leech protein hydrolysates
Discovery pipeline published in Molecules (2025)
Abstract
Medicinal plants and animal-derived proteins represent valuable natural sources of bioactive components with pharmaceutical potential. Whilst some medicinal plants and animal-derived proteins also offer rich sources of anticoagulant bioactive peptides, their development faces multiple challenges: anticoagulant evaluation relies on single-parameter assays with limited reliability, native proteins demonstrate suboptimal activity without enzymatic treatment, and few researchers investigate bioavailable peptides. Our study establishes an innovative framework using the leech as a case study to overcome these barriers. A novel anticoagulant evaluation model was first established with the Critic-G1 weighting method. And we optimized the enzymatically hydrolyzed extracts with high activity using Box-Behnken response surface methodology. Subsequently, the everted gut sac model was implemented to simulate intestinal absorption and screen for absorbable peptide fractions. Furthermore, peptidomics was employed to identify the bioactive peptides. Lastly, we identified the bioactivity using anticoagulation assays. Results indicated that the optimal hydrolysis conditions were achieved with trypsin at 50.48 °C, an enzyme-to-substrate ratio of 6.78%, 7.51 h, and pH of 8.06. The peptide DLRWM was identified through integrated peptidomics and molecular docking approaches, with subsequent activity validation demonstrating its potent anticoagulant effects. This study has successfully identified a novel anticoagulant peptide (DLRWM) with confirmed intestinal absorption properties and provides a template for unlocking the pharmaceutical potential of medicinal animal proteins.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Integrated discovery strategy combining enzymatic hydrolysis, fractionation, in vitro assays, and bioinformatic screening to identify orally absorbable anticoagulant peptides from Whitmania pigra.
Por qué esto importa para la hirudoterapia
Este estudio estableció un marco integrado para descubrir péptidos anticoagulantes absorbibles utilizando la sanguijuela como caso de estudio, combinando hidrólisis enzimática optimizada (tripsina, 50,48 °C, relación enzima-sustrato 6,78 %, 7,51 h, pH 8,06), un modelo de saco intestinal evertido para la absorción intestinal simulada, peptidómica y acoplamiento molecular. Los investigadores identificaron un nuevo pentapéptido, DLRWM, con efectos anticoagulantes validados y propiedades de absorción intestinal confirmadas, proporcionando una plantilla para desbloquear el potencial farmacéutico de las proteínas de animales medicinales. Este trabajo es relevante para el dominio de ASH, ya que explora sistemáticamente las proteínas derivadas de sanguijuelas como fuente de péptidos anticoagulantes biodisponibles por vía oral. Sin embargo, la actividad anticoagulante se validó únicamente mediante ensayos in vitro y modelos de absorción simulada; no se presentan datos de eficacia in vivo, farmacocinéticos ni clínicos.
Citación
A novel integrated strategy for discovering absorbable anticoagulant bioactive peptides: a case study on leech protein hydrolysates.
Fang KX et al. · Molecules, 2025
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026