Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen.
10.1016/j.apsb.2024.12.038
- Author:
Chuanjing CHENG
1
;
Kaixin LIU
1
;
Jinling ZHANG
1
;
Yanqi HAN
2
;
Tiejun ZHANG
2
;
Yuanyuan HOU
1
;
Gang BAI
1
Author Information
1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.
2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Key Laboratory of Quality Markers of Traditional Chinese Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin 300462, China.
- Publication Type:Journal Article
- Keywords:
Blood circulation;
Collagen;
Ginsenoside CK;
PHD2;
PHD2 inhibitor;
Platelet adhesion;
Thrombotic diseases;
Von willebrand factor
- From:
Acta Pharmaceutica Sinica B
2025;15(3):1497-1513
- CountryChina
- Language:English
-
Abstract:
Platelets are indispensable for physiological hemostasis and pathological thrombus formation, and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation, often overlooked in current antiplatelet therapies. This study aims to elucidate how ginsenoside CK enhances hemodynamic circulation, alleviates stasis, and proposes therapeutic mechanisms. Inspired by the effects on improving microcirculatory disturbances in an acute soft tissue injury model, CK was identified as a PHD2 inhibitor, effectively suppressing platelet adhesion to collagen. It was proposed that targeting PHD2 regulates collagen hydroxylation modification, thereby influencing the formation of its three-dimensional structure, reducing the binding affinity between VWF and collagen, and ultimately suppressing thrombotic events. The efficacy of this mechanism was subsequently confirmed through a mouse DIC model, demonstrating the feasibility of CK in alleviating circulatory disorders. It is worth noting that when Phd2 was knocked down in mice's lungs, pulmonary embolism was significantly reduced. Additionally, PHD2 inhibitors approved for other diseases have exhibited similar anti-thrombotic effects. Moreover, when PHD2 inhibitors were combined with aspirin, they more effectively inhibited arterial thrombosis in rats. The findings offer valuable insights into potential targets for developing antiplatelet drugs or expanding therapeutic applications for existing PHD2 inhibitors in treating thrombotic diseases.
