@article{Yang2026, 
author = {Jieru Yang and Lihan Zhang and Jiasen Ye and Ruicheng Yan and Xiancheng Qiu and Lifang Zhang and Yong Jiang and Jianhua Peng},
title = {Integrated network pharmacology reveals the mechanisms of punicalagin in cardiovascular and cerebrovascular diseases treatment},
year = {2026},
journal = {Brain Hemorrhages},
volume = {7},
number = {1},
pages = {7-19},
keywords = {Punicalagin, Coronary Artery disease, Myocardial Infarction, Carotid Atherosclerosis, Cerebral Ischemic Stroke, Network Pharmacology},
url = {https://www.sciopen.com/article/10.1016/j.hest.2025.06.001},
doi = {10.1016/j.hest.2025.06.001},
abstract = {ObjectiveCardiovascular 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.MethodsThis study employed integrated network pharmacology, molecular docking, and experimental validation to identify PU’s multi-target mechanisms.ResultsPU 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.ConclusionOur 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.}
}