Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen
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 h...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383524004957 |
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| author | Chuanjing Cheng Kaixin Liu Jinling Zhang Yanqi Han Tiejun Zhang Yuanyuan Hou Gang Bai |
| author_facet | Chuanjing Cheng Kaixin Liu Jinling Zhang Yanqi Han Tiejun Zhang Yuanyuan Hou Gang Bai |
| author_sort | Chuanjing Cheng |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2a7f9b2e899840bda161af20db18d486 |
| institution | DOAJ |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-2a7f9b2e899840bda161af20db18d4862025-08-20T03:07:58ZengElsevierActa Pharmaceutica Sinica B2211-38352025-03-011531497151310.1016/j.apsb.2024.12.038Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagenChuanjing Cheng0Kaixin Liu1Jinling Zhang2Yanqi Han3Tiejun Zhang4Yuanyuan Hou5Gang Bai6State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState 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, ChinaState 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, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China; Corresponding authors.State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2211383524004957PHD2Platelet adhesionCollagenPHD2 inhibitorGinsenoside CKBlood circulation |
| spellingShingle | Chuanjing Cheng Kaixin Liu Jinling Zhang Yanqi Han Tiejun Zhang Yuanyuan Hou Gang Bai Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen Acta Pharmaceutica Sinica B PHD2 Platelet adhesion Collagen PHD2 inhibitor Ginsenoside CK Blood circulation |
| title | Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen |
| title_full | Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen |
| title_fullStr | Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen |
| title_full_unstemmed | Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen |
| title_short | Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen |
| title_sort | ginsenoside ck targets phd2 to prevent platelet adhesion and enhance blood circulation by modifying the three dimensional arrangement of collagen |
| topic | PHD2 Platelet adhesion Collagen PHD2 inhibitor Ginsenoside CK Blood circulation |
| url | http://www.sciencedirect.com/science/article/pii/S2211383524004957 |
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