Integrated network pharmacology reveals the mechanisms of punicalagin in cardiovascular and cerebrovascular diseases treatment

Cardiovascular and cerebrovascular diseases, including coronary artery disease (CAD), myocardial infarction (MI), carotid atherosclerosis (CAS), and cerebral ischemic stroke (CIS), continue to impose a significant global health burden due to the limited therapeutic efficacy of current clinical interventions. Punicalagin (PU), a pomegranate-derived polyphenol with antioxidant and anti-inflammatory properties, exhibits therapeutic potential but requires mechanistic clarification.

This study employed integrated network pharmacology, molecular docking, and experimental validation to identify PU’s multi-target mechanisms.

PU has 519 potential targets and shares 185 common targets with CAD, MI, CAS, and CIS. Molecular docking analysis showed that PU had strong binding affinity with HIF-1α, CASPASE3 and TLR4 targets. Experimental validation using the OGD/R model in HT22 cells revealed that PU treatment significantly reduced reactive oxygen species (ROS) levels and apoptosis, while downregulating the expression of HIF-1α, CASPASE3 and TLR4. PU plays a critical role in cardiovascular and cerebrovascular diseases through the modulation of pathways associated with HIF-1α, CASPASE3 and TLR4.

Our study revealed the therapeutic effects and underlying mechanisms of PU on CAD, MI, CAS, and CIS, providing a foundation for subsequent in vivo and clinical studies on PU as a potential therapeutic agent.