α- and γ-mangostin cause shape changes, inhibit aggregation and induce cytolysis of rat platelets.
α- and γ-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 α- and γ-mangostin on platelets were investigated based on their possible antiplatelet activity. Treatment of isolated platelets with α-mangostin resulted in attenuation of platelet aggregatory response to collagen, thrombin or ADP. Such antiaggregatory effects were concentration-dependent in ranges of 1-10 μM. Interestingly, α-mangostin alone induced shape changes in platelets at the same concentration, and higher levels, 25 and 50 μM caused platelet lysis. Similarly, γ-mangostin induced shape changes and inhibited aggregation at 2.5-25 μM, while 50 and 100 μM γ-mangostin exhibited cytotoxicity. Platelet shape change induced by α- and γ-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 Ca(2+) chelating with BAPTA-AM and extracellular Ca(2+) removal. Cytolysis by both α- and γ-mangostin was abolished in the absence of extracellular Ca(2+). Taken together, α- and γ-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 Ca(2+) influx. These results suggest that mangosteen consumption may have potential platelet effects, although the in vivo or clinical consequences have yet to be assessed.
College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, Republic of Korea.
Yingqiu
Y
Liu
College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, Republic of Korea.
Jung-Min
JM
Park
College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, Republic of Korea.
Kyung-Hwa
KH
Chang
College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, Republic of Korea.
Young-Won
YW
Chin
College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, Republic of Korea. Electronic address: mlee@dongguk.edu.
Moo-Yeol
MY
Lee
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002449:Cell Aggregation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D044004:Xanthones / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D044004:Xanthones; C021053:mangostin
Aggregation; Cytotoxicity; Platelets; Shape change; α-Mangostin; γ-Mangostin