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.
Summary
Integrated network pharmacology and experimental validation showing hirudin suppresses myocardial hypertrophy via TNF-α and MAPK pathway inhibition.
Why This Matters for Hirudotherapy
This study combined network pharmacology prediction with in vitro validation to examine hirudin's effect on myocardial hypertrophy, demonstrating that hirudin inhibited AngII-induced hypertrophy in H9c2 cells and primary rat cardiomyocytes, reducing STAT3, MAPK1, and IL-6 expression, with PI3K/AKT identified as a key pathway. For ASH's domain, this is relevant as it explores a leech-derived peptide in cardiovascular disease. However, the work is entirely in vitro (cell lines and primary cardiomyocytes) with no animal or human data, and network pharmacology predictions require further biological validation. The therapeutic relevance to actual hirudotherapy or leech secretome application remains unestablished and indirect.
Citation
Network pharmacology and experimental verification reveal the mechanism of hirudin in suppressing myocardial hypertrophy.
Liu M et al. · Frontiers in pharmacology, 2022
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