Related Experiment Video
Updated: Jun 1, 2025
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Polydatin mitigates thrombosis by inhibiting PHD2-induced proline hydroxylation on collagen, reducing platelet
Kaixin Liu1, Chuanjing Cheng1, Jin Yan1
1State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, PR China.
Background:
Platelet adhesion to collagen, a critical initial step in thrombus formation, remains an underexplored therapeutic target in thrombosis. Current disease treatment strategies primarily focus on platelet activation and aggregation, often overlooking the crucial initial adhesion phase. Reynoutria japonica (Huzhang, HZ), utilized in traditional Chinese medicine to enhance blood circulation and resolve blood stasis, lacks comprehensive insights into its active components and their anti-thrombotic mechanisms.
Purpose:
This study investigated the antithrombotic effects and mechanisms of polydatin, a stilbene derived from HZ, with a focus on its effect on platelet adhesion.
Methods:
An acute pulmonary infection model was used, along with metabolomic and proteomic analyses, to investigate the antithrombotic efficacy of the active component polydatin and identify its targets. Chemical biology, protein mass spectrometry analyses, and molecular interaction analysis were performed to investigate its mechanism. Multiple models of circulatory disorders, including disseminated intravascular coagulation (DIC) and atherosclerosis in mice, with or without targeted gene knockdown, were employed to assess the role of polydatin in modulating platelet adhesion.
Results:
Our investigation revealed that polydatin targets prolyl hydroxylase 2 (PHD2), thereby inhibiting hydroxylation of proline residues on collagen. This disruption in collagen assembly and the von Willebrand factor (VWF)-collagen interaction reduces platelet adhesion, significantly impacting circulation in both DIC and atherosclerosis. This represents a novel mechanism of antithrombotic action, distinct from currently available therapies.
Conclusion:
Targeting PHD2 to modulate collagen structure and platelet adhesion presents a promising novel therapeutic strategy for thrombosis-related circulatory disorders.
Insights
Polydatin, derived from Reynoutria japonica, inhibits platelet adhesion by targeting prolyl hydroxylase 2 (PHD2). This novel mechanism offers a promising therapeutic strategy for thrombosis and related circulatory disorders.
Area of Science:
- Biochemistry
- Pharmacology
- Vascular Biology
Background:
- Platelet adhesion to collagen is a critical, yet underexplored, therapeutic target in thrombosis.
- Current treatments focus on platelet activation and aggregation, neglecting the initial adhesion phase.
- Reynoutria japonica (HZ) has traditional uses, but its anti-thrombotic components and mechanisms are not well understood.
Purpose of the Study:
- To investigate the antithrombotic effects and mechanisms of polydatin, an active component of HZ.
- To specifically examine polydatin's impact on platelet adhesion.
Main Methods:
- Utilized acute pulmonary infection, disseminated intravascular coagulation (DIC), and atherosclerosis mouse models.
- Employed metabolomic, proteomic, chemical biology, and mass spectrometry analyses.
- Investigated polydatin's mechanism via molecular interaction analysis and gene knockdown.
Main Results:
- Polydatin targets prolyl hydroxylase 2 (PHD2), inhibiting collagen hydroxylation.
- This action disrupts collagen assembly and von Willebrand factor (VWF)-collagen interaction, reducing platelet adhesion.
- Demonstrated significant impact on circulation in DIC and atherosclerosis models, revealing a novel anti-thrombotic mechanism.
Conclusions:
- Targeting PHD2 to modulate collagen structure and platelet adhesion is a novel therapeutic strategy.
- This approach shows promise for treating thrombosis-related circulatory disorders.
- Polydatin represents a potential therapeutic agent for addressing unmet needs in antithrombotic therapy.
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