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.
Highlights
Garcinol, a polyisoprenylated benzophenone [1,2] isolated from Garcinia cambogia [2] or Garcinia indica [1,3,4], counteracts oxidative stress and inflammation [3]
Garcinol is effective against cancer in part by stimulating apoptosis [7,8,9,10], an effect paralleled by Toxins 2019, 11, 382; doi:10.3390/toxins11070382
Garcinol further stimulates the suicidal death of erythrocytes or eryptosis, an effect paralleled by oxidative stress and Ca2+ entry [16]
Summary
A polyisoprenylated benzophenone [1,2] isolated from Garcinia cambogia [2] or Garcinia indica [1,3,4], counteracts oxidative stress and inflammation [3]. Garcinol is effective against cancer in part by stimulating apoptosis [7,8,9,10], an effect paralleled by Toxins 2019, 11, 382; doi:10.3390/toxins11070382 www.mdpi.com/journal/toxins. Garcinol has further been shown to counteract lipid peroxidation [2] and lipoxygenase activity [15]. Garcinol further stimulates the suicidal death of erythrocytes or eryptosis, an effect paralleled by oxidative stress and Ca2+ entry [16]. The putative effect on liver injury [6] and neurodegeneration [5] was attributed to inhibition of apoptosis
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