alpha- and gamma-mangostin cause shape changes, inhibit aggregation and induce cytolysis of rat platelets

Abstract

alpha- and gamma-mangostin are natural xanthones isolated from mangosteen (Garcinia mangostana) and the major constituents responsible for the plant's diverse biological activities. In this study, the effects of alpha- and gamma-mangostin on platelets were investigated based on their possible antiplatelet activity. Treatment of isolated platelets with alpha-mangostin resulted in attenuation of platelet aggregatory response to collagen, thrombin or ADP. Such antiaggregatory effects were concentration-dependent in ranges of 1-10 mu M. Interestingly, alpha-mangostin alone induced shape changes in platelets at the same concentration, and higher levels, 25 and 50 mu M caused platelet lysis. Similarly, gamma-mangostin induced shape changes and inhibited aggregation at 2.5-25 mu M, while 50 and 100 mu M gamma-mangostin exhibited cytotoxicity. Platelet shape change induced by alpha- and gamma-mangostin was accompanied by increases in myosin light chain (MLC) phosphorylation. MLC phosphorylation and subsequent shape changes were prevented by pretreatment with Rho kinase (ROCK) inhibitor Y-27632, but not by the intracellular Ca2+ chelating with BAPTA-AM and extracellular Ca2+ removal. Cytolysis by both alpha- and gamma-mangostin was abolished in the absence of extracellular Ca2+. Taken together, alpha- and gamma-mangostin have differential effects on platelets depending on their concentration, which includes inducing shape change, inhibiting aggregation and causing cytolysis. Platelet shape change is attributed to stimulation of the Rho/ROCK signaling pathway, while platelet lysis is presumably mediated by extracellular Ca2+ influx. These results suggest that mangosteen consumption may have potential platelet effects, although the in vivo or clinical consequences have yet to be assessed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.