دورية أكاديمية
أعرض في EDS

Icaritin Sensitizes Thrombin- and TxA2-Induced Platelet Activation and Promotes Hemostasis via Enhancing PLCγ2-PKC Signaling Pathways.

التفاصيل البيبلوغرافية
العنوان: Icaritin Sensitizes Thrombin- and TxA2-Induced Platelet Activation and Promotes Hemostasis via Enhancing PLCγ2-PKC Signaling Pathways.
المؤلفون: Zhu Z; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China., Luo Y; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China., Liao H; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China., Guo R; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China., Hao D; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China., Lu Z; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China., Huang M; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China., Sun C; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi City, Shandong Province, China., Yao J; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi City, Shandong Province, China., Wei N; Department of Oncology and Cancer Therapeutics Program, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, United States., Zeng K; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China., Tu P; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China., Zhang G; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi City, Shandong Province, China.
المصدر: Thrombosis and haemostasis [Thromb Haemost] 2024 Aug; Vol. 124 (8), pp. 753-769. Date of Electronic Publication: 2024 Jan 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Thieme Country of Publication: Germany NLM ID: 7608063 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2567-689X (Electronic) Linking ISSN: 03406245 NLM ISO Abbreviation: Thromb Haemost Subsets: MEDLINE
أسماء مطبوعة: Publication: 2018- : Stuttgart : Thieme
Original Publication: Stuttgart, Schattauer.
مواضيع طبية MeSH: Phospholipase C gamma*/metabolism , Signal Transduction*/drug effects , Thromboxane A2*/metabolism , Platelet Activation*/drug effects , Hemostasis*/drug effects , Thrombin*/metabolism , Blood Platelets*/metabolism , Blood Platelets*/drug effects , Protein Kinase C*/metabolism , Flavonoids*/pharmacology , Platelet Aggregation*/drug effects , Platelet Glycoprotein GPIIb-IIIa Complex*/metabolism, Animals ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; Hemorrhage/chemically induced ; Hemorrhage/drug therapy ; Bleeding Time
مستخلص: Background:  Vascular injury results in uncontrollable hemorrhage in hemorrhagic diseases and excessive antithrombotic therapy. Safe and efficient hemostatic agents which can be orally administered are urgently needed. Platelets play indispensable roles in hemostasis, but there is no drug exerting hemostatic effects through enhancing platelet function.
Methods:  The regulatory effects of icaritin, a natural compound isolated from Herba Epimedii , on the dense granule release, thromboxane A 2 (TxA 2 ) synthesis, α-granule release, activation of integrin αIIbβ3, and aggregation of platelets induced by multiple agonists were investigated. The effects of icaritin on tail vein bleeding times of warfarin-treated mice were also evaluated. Furthermore, we investigated the underlying mechanisms by which icaritin exerted its pharmacological effects.
Results:  Icaritin alone did not activate platelets, but significantly potentiated the dense granule release, α-granule release, activation of integrin αIIbβ3, and aggregation of platelets induced by thrombin and U46619. Icaritin also shortened tail vein bleeding times of mice treated with warfarin. In addition, phosphorylated proteome analysis, immunoblotting analysis, and pharmacological research revealed that icaritin sensitized the activation of phospholipase Cγ2 (PLCγ2)-protein kinase C (PKC) signaling pathways, which play important roles in platelet activation.
Conclusion:  Icaritin can sensitize platelet activation induced by thrombin and TxA 2 through enhancing the activation of PLCγ2-PKC signaling pathways and promote hemostasis, and has potential to be developed into a novel orally deliverable therapeutic agent for hemorrhages.
Competing Interests: None declared.
(Thieme. All rights reserved.)
معلومات مُعتمدة: 81603361 National Natural Science Foundation of China; ZR2022LZY021 Natural Science Foundation of Shandong Province
المشرفين على المادة: EC 3.1.4.3 (Phospholipase C gamma)
UFE666UELY (icaritin)
57576-52-0 (Thromboxane A2)
EC 3.4.21.5 (Thrombin)
EC 2.7.11.13 (Protein Kinase C)
0 (Flavonoids)
0 (Platelet Glycoprotein GPIIb-IIIa Complex)
تواريخ الأحداث: Date Created: 20240115 Date Completed: 20240719 Latest Revision: 20240724
رمز التحديث: 20240726
DOI: 10.1055/a-2245-8457
PMID: 38224965
قاعدة البيانات: MEDLINE
الوصف
تدمد:2567-689X
DOI:10.1055/a-2245-8457