Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation
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 wit...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861320300669 |
| _version_ | 1818112824653643776 |
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| author | Yue Ming Guang Xin Beihong Ji Chengji Ji Zeliang Wei Boli Zhang Junhua Zhang Kui Yu Xiaoyu Zhang Shiyi Li Youping Li Zhihua Xing Hai Niu Wen Huang |
| author_facet | Yue Ming Guang Xin Beihong Ji Chengji Ji Zeliang Wei Boli Zhang Junhua Zhang Kui Yu Xiaoyu Zhang Shiyi Li Youping Li Zhihua Xing Hai Niu Wen Huang |
| author_sort | Yue Ming |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T03:25:05Z |
| format | Article |
| id | doaj.art-3241a1d8e1fc41fab36cdf44175cc715 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-11T03:25:05Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-3241a1d8e1fc41fab36cdf44175cc7152022-12-22T01:22:32ZengElsevierJournal of Pharmacological Sciences1347-86132020-09-0114414351Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formationYue Ming0Guang Xin1Beihong Ji2Chengji Ji3Zeliang Wei4Boli Zhang5Junhua Zhang6Kui Yu7Xiaoyu Zhang8Shiyi Li9Youping Li10Zhihua Xing11Hai Niu12Wen Huang13Laboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pennsylvania, United StatesClinical Laboratory, Hospital of University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Corresponding author. Keyuan Road 4 No.1, Gaopeng Avenue, Gaoxin District, Chengdu, Sichuan, 610041, China. Fax: +86 028 85164073.Laboratory of Ethnopharmacology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Corresponding author. Keyuan Road 4 No.1, Gaopeng Avenue, Gaoxin District, Chengdu, Sichuan, 610041, China. Fax: +86 028 85164073.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.http://www.sciencedirect.com/science/article/pii/S1347861320300669EntecavirPlateletP2X7 receptorMitochondriaOxidative stress |
| spellingShingle | Yue Ming Guang Xin Beihong Ji Chengji Ji Zeliang Wei Boli Zhang Junhua Zhang Kui Yu Xiaoyu Zhang Shiyi Li Youping Li Zhihua Xing Hai Niu Wen Huang Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation Journal of Pharmacological Sciences Entecavir Platelet P2X7 receptor Mitochondria Oxidative stress |
| title | Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation |
| title_full | Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation |
| title_fullStr | Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation |
| title_full_unstemmed | Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation |
| title_short | Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation |
| title_sort | entecavir as a p2x7r antagonist ameliorates platelet activation and thrombus formation |
| topic | Entecavir Platelet P2X7 receptor Mitochondria Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S1347861320300669 |
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