Pharmacological mechanisms and therapeutic potential of Puerarin in post-stroke rehabilitation: Insights from network pharmacology and experimental validation.

BACKGROUND

Stroke is a leading cause of disability, and promoting post-stroke recovery through endothelial regeneration and angiogenesis is crucial for improving patient outcomes. Puerarin, a flavonoid derived from Pueraria lobata, has shown promise in enhancing angiogenesis and endothelial function. This study investigates the pharmacological mechanisms of Puerarin in post-stroke rehabilitation through network pharmacology and experimental validation.

METHODS

Network pharmacology was used to identify potential gene targets of Puerarin and their association with post-stroke sequelae. A Venn diagram analysis identified 116 common targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify enriched pathways. Molecular docking simulations were used to confirm interactions between Puerarin and key targets. Additionally, in vitro experiments using human umbilical vein endothelial cells (HUVECs) exposed to oxygen-glucose deprivation/re-oxygenation (OGD/R) were conducted to assess Puerarin's effects on cell migration, proliferation, and angiogenesis.

RESULTS

Network pharmacology revealed several key pathways, with the HIF-1α/VEGF signaling pathway identified as a critical target. Experimental validation confirmed that Puerarin enhanced endothelial cell migration, proliferation, and angiogenesis in a concentration-dependent manner. At lower concentrations, Puerarin promoted angiogenesis and endothelial migration. Molecular docking simulations demonstrated favorable binding interactions between Puerarin and key angiogenic targets.

CONCLUSIONS

Puerarin may serve as a therapeutic agent for post-stroke rehabilitation, promoting vascular regeneration through endothelial cell migration and angiogenesis. Its ability to activate the HIF-1α/VEGF pathway underscores its potential in improving functional recovery. Further in vivo studies are required to optimize dosing, assess long-term efficacy, and explore clinical applications.