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Updated: Dec 15, 2025
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation
Yue Ming1, Guang Xin1, Beihong Ji2
1Laboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract:
Platelet activation is the primary cause of thrombosis. The P2X7 receptor (P2X7R) is a therapeutic target of thrombosis. However, it is still unknown whether P2X7R activation affects platelet thrombus. Our molecular docking results showed that entecavir as a P2X7R antagonist interacted perfectly with the human P2X7R (hP2X7R) in silico simulation studies. Furthermore, our experimental data revealed that entecavir could act as a P2X7R antagonist to exert cytoprotective effects against platelet activation via protecting mitochondrial function, improving lipid peroxidation and increasing antioxidant activity. Correlated with this, entecavir inhibited platelet aggregation, dense-granule secretion, P-selectin expression, integrin activation and Ca2+ increase. In experimental mouse model, entecavir could significantly inhibit arteriovenous thrombosis and prolong the bleeding time. Furthermore, we found that entecavir had no significant effect on prothrombin time (PT), activated partial thrombin time (APTT), thrombin time (TT), fibrinogen (FIB), mean platelet volume (MPV) and platelet counts (PLT). This study demonstrates that entecavir markedly prevents platelet activation and thrombosis through inhibiting P2X7R without affecting coagulation system. Therefore, entecavir may be a potential candidate for treating thrombosis disease.
Insights
Entecavir, a P2X7 receptor antagonist, effectively inhibits platelet activation and thrombosis by protecting mitochondrial function. This study suggests entecavir as a potential treatment for thrombosis without impacting the coagulation system.
Area of Science:
- Biochemistry
- Pharmacology
- Hematology
Background:
- Platelet activation is central to thrombosis, a major health concern.
- The P2X7 receptor (P2X7R) is a potential therapeutic target for thrombosis.
- The role of P2X7R activation in platelet thrombus formation requires further investigation.
Purpose of the Study:
- To investigate the potential of entecavir as a P2X7R antagonist in preventing platelet activation and thrombosis.
- To elucidate the mechanisms by which entecavir affects platelet function and thrombosis.
- To evaluate the safety and efficacy of entecavir in a mouse model of thrombosis.
Main Methods:
- In silico molecular docking to assess entecavir's interaction with human P2X7R (hP2X7R).
- In vitro experiments measuring platelet aggregation, dense-granule secretion, P-selectin expression, integrin activation, and intracellular calcium increase.
- In vivo assessment using an experimental mouse model of arteriovenous thrombosis and bleeding time analysis.
- Evaluation of entecavir's effect on coagulation parameters (PT, APTT, TT, FIB) and platelet indices (MPV, PLT).
Main Results:
- Molecular docking confirmed entecavir's perfect interaction with hP2X7R.
- Entecavir demonstrated cytoprotective effects against platelet activation by preserving mitochondrial function, reducing lipid peroxidation, and enhancing antioxidant activity.
- Entecavir significantly inhibited platelet aggregation, secretion, P-selectin expression, integrin activation, and Ca2+ influx.
- In vivo, entecavir markedly reduced arteriovenous thrombosis and prolonged bleeding time.
- Entecavir did not significantly affect key coagulation parameters or platelet counts.
Conclusions:
- Entecavir acts as a P2X7R antagonist, effectively inhibiting platelet activation and thrombosis.
- The mechanism involves protection of mitochondrial function and antioxidant properties.
- Entecavir shows potential as a therapeutic agent for thrombosis without compromising the coagulation system.
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