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Open AccessArticle

Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis

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
*
Author to whom correspondence should be addressed.
Both authors contributed equally and thus share first authorship.
Toxins 2019, 11(7), 382; https://doi.org/10.3390/toxins11070382
Received: 11 April 2019 / Revised: 18 June 2019 / Accepted: 21 June 2019 / Published: 1 July 2019
(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)
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Abstract

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. View Full-Text
Keywords: CRP; platelet activation; degranulation; integrin; cytosolic Ca2+ concentration; caspase; phosphatidylserine translocation CRP; platelet activation; degranulation; integrin; cytosolic Ca2+ concentration; caspase; phosphatidylserine translocation
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Cao, H.; Al Mamun Bhuyan, A.; Umbach, A.T.; Ma, K.; Borst, O.; Gawaz, M.; Zhang, S.; Nürnberg, B.; Lang, F. Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis. Toxins 2019, 11, 382.

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