Network pharmacology and experimental verification reveal the mechanism of hirudin in suppressing myocardial hypertrophy
Mechanism study published in Frontiers in Pharmacology (2022)
Abstract
Background: Myocardial hypertrophy is a complex pathological process, which is a common manifestation during the development of various cardiovascular diseases. Hirudin has been shown to have therapeutic effects on a variety of cardiovascular diseases, however, its therapeutic effect on myocardial hypertrophy is still unknown, and its chemical and pharmacological characteristics remain to be elucidated. Methods: In this study, the network pharmacology method was used to characterize the mechanism of hirudin on myocardial hypertrophy. The potential protein targets of hirudin and myocardial hypertrophy were both obtained from the Genecards database, and potential pathways associated with genes were identified by Gene Ontology and pathway enrichment analysis, and the data were displayed in a visual manner. Subsequently, the potential mechanism of action of hirudin on myocardial hypertrophy predicted by network pharmacology analysis was verified by molecular docking, and finally, the main findings were further verified by in vitro experiments by molecular biology techniques. Based on the results obtained from the study of H9c2 cell line, the inhibitory effect of hirudin on myocardial hypertrophy was further proved in the primary rat cardiomyocytes. Results: A total of 250 targets of hirudin, and 5,376 targets related to myocardial hypertrophy after deduplication were collected. The drug-disease network showed the relationship between hirudin, myocardial hypertrophy, and the targets. Further, systematic analysis from the PPI network indicated that blood coagulation, vesicle lumen, and signaling receptor activator activity may be the potential mechanisms of hirudin in the treatment of myocardial hypertrophy, and the PI3K/AKT signaling pathway may be the most relevant to the therapeutic effect of hirudin. Then, three therapeutic targets that were highly related to myocardial hypertrophy were extracted. Hirudin can be highly bound to STAT3, IL-6, and MAPK1 and found by molecular docking, which may be the basis for its inhibitory effect on myocardial hypertrophy. In addition, in vitro experiments showed that hirudin could inhibit AngII-induced hypertrophy and death of H9c2 cells, and significantly reduce the mRNA and protein expression levels of STAT3, MAPK1, and IL-6. The above conclusions were verified in primary rat cardiomyocytes. Conclusion: Hirudin can be used to treat myocardial hypertrophy through a complex mechanism. The application of network pharmacology and experimental validation can promote the application of hirudin in cardiovascular diseases and the interpretation and understanding of molecular biological mechanisms.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Integrated network pharmacology and experimental validation showing hirudin suppresses myocardial hypertrophy via TNF-α and MAPK pathway inhibition.
Por qué esto importa para la hirudoterapia
Este estudio combinó predicción mediante farmacología de redes con validación in vitro para examinar el efecto de la hirudina sobre la hipertrofia miocárdica, demostrando que la hirudina inhibió la hipertrofia inducida por AngII en células H9c2 y en cardiomiocitos primarios de rata, reduciendo la expresión de STAT3, MAPK1 e IL-6, e identificando la vía PI3K/AKT como una vía clave. Para el dominio de la ASH, esto es relevante, ya que explora un péptido derivado de la sanguijuela en enfermedad cardiovascular. Sin embargo, el trabajo es enteramente in vitro (líneas celulares y cardiomiocitos primarios), sin datos animales ni humanos, y las predicciones de la farmacología de redes requieren validación biológica adicional. La relevancia terapéutica para la hirudoterapia real o para la aplicación del secretoma de la sanguijuela sigue sin establecerse y es indirecta.
Citación
Network pharmacology and experimental verification reveal the mechanism of hirudin in suppressing myocardial hypertrophy.
Liu M et al. · Frontiers in pharmacology, 2022
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026