机构：[1]Department of Pharmacology & Experimental Therapy, University of Tübingen, 72074 Tübingen, Germany[2]Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, 72076 Tübingen, Germany[3]Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China[4]Department of Vegetative & Clinical Physiology, University of Tübingen, 72074 Tübingen, Germany
Garcinol, an anti-inflammatory and anti-carcinogenic polyisoprenylated benzophenone isolated from Garcinia plants, stimulates tumor cell apoptosis and suicidal erythrocyte death, but supports the survival of hepatocytes and neurons. The present study explored whether the substance influences platelet function and/or apoptosis. To this end, we exposed murine blood platelets to garcinol (33 µM, 30 min) without and with activation by collagen-related peptide (CRP) (2-5 µg/mL) or thrombin (0.01 U/mL); flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance from annexin-V-binding, relative platelet volume from forward scatter, and aggregation utilizing staining with CD9-APC and CD9-PE. As a result, in the absence of CRP and thrombin, the exposure of the platelets to garcinol did not significantly modify [Ca2+]i, P-selectin abundance, activated αIIbβ3 integrin, annexin-V-binding, cell volume, caspase activity, and aggregation. Exposure of platelets to CRP or thrombin was followed by a significant increase of [Ca2+]i, P-selectin abundance, αIIbβ3 integrin activity, annexin-V-binding, caspase activity, and aggregation, as well as significant cell shrinkage. All effects of CRP were strong and significant; those of thrombin were only partially and slightly blunted in the presence of garcinol. In conclusion, garcinol blunts CRP-induced platelet activity, apoptosis and aggregation.
基金：
This project was supported by the Deutsche Forschungsgemeinschaft (Klinische Forschungsgruppe-
KFO-274: “Platelets-Molecular Mechanisms and Translational Implications”) and by the Deutsche
Forschungsgemeinschaft (DFG, German Research Foundation)—Project number 374031971—TRR 240, by the
DFG grant “Gi proteins and platelets” (NU 53/13-1), by the Institutional Strategy of the University of Tuebingen
(Deutsche Forschungsgemeinschaft, ZUK63), and by the Open Access Publishing Fund of Tuebingen University.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|2 区医学
小类|2 区食品科技2 区毒理学
最新[2023]版：
大类|3 区医学
小类|2 区食品科技2 区毒理学
第一作者：
第一作者机构：[1]Department of Pharmacology & Experimental Therapy, University of Tübingen, 72074 Tübingen, Germany
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Cao Hang,Al Mamun Bhuyan Abdulla,Umbach Anja T,et al.Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis.[J].Toxins.2019,11(7):doi:10.3390/toxins11070382.
APA：
Cao Hang,Al Mamun Bhuyan Abdulla,Umbach Anja T,Ma Ke,Borst Oliver...&Lang Florian.(2019).Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis..Toxins,11,(7)
MLA：
Cao Hang,et al."Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis.".Toxins 11..7(2019)
