Leech-Derived Hirudin in Yangyin Tongnao Granules: Network Pharmacology Peels Back the Layers of Its Ischemic Stroke Relief Action

Abstract

Background: This study applied network pharmacology to explore the mechanism of Yangyin Tongnao Granules (YYTN) and its key component hirudin in improving cerebral ischemia-reperfusion injury (CIRI). Methods: From Traditional Chinese Medicine (TCM) Systems Pharmacology and the literature, the active components of 6 herbs of YYTN were obtained; the targets were obtained based on their sources (the target of leech came from GeneCards, and the other 5 TCM came from HERB, totaling 2879); the CIRI targets were obtained from DisGeNet (300) and GeneCards (144, with a score > 1) (a total of 420). The "TCM - component - target" network and protein-protein interaction (PPI) network (Search Tool for the Retrieval of Interaction Gene/Proteins, confidence = 0.4) were constructed. The core targets were screened using the Matthews Correlation Coefficient method; Kyoto Encyclopedia of Genes and Genomes (KEGG)/Gene Ontology (GO) enrichment analysis was performed on the core targets and 13 targets of hirudin. Results: The "TCM - Components - Targets" network contained 6 TCM, 251 components, and 198 targets; the PPI network had 196 nodes and 4760 edges. The top 5 core targets were tumor protein P53 (TP53), Jun proto-oncogene (JUN), Fos proto-oncogene (FOS), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B P65 subunit (RELA); the core targets were enriched in 152 pathways in KEGG, while the hirudin target was enriched in 31 pathways and in 487 GO entries. Conclusions: YYTN can improve CIRI through multiple components, multiple targets and multiple pathways. Hirudin may exert its effect through pathways such as complement and coagulation cascades.