Differential effects of ganodermic acid S on the thromboxane A2-signaling pathways in human platelets.

Ganodermic acid S (GAS) [lanosta-7,9(11),24-triene-3beta,15alpha-diacetoxy-26-oic acid], isolated from the Chinese medicinal fungus Ganoderma lucidum (Fr.) Karst (Polyporaceae), exerted a concentration-dependent inhibition on the response of human gel-filtered platelets (GFP) to U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2alpha), a thromboxane (TX) A2 mimetic. GAS at 2 microM inhibited 50% of cell aggregation. GAS at 7.5 microM inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of alpha-granule secretion, and over 95% of aggregation. GAS also strongly inhibited U46619-induced diacylglycerol formation, arachidonic acid release, and TXB2 formation. An immunoblotting study of protein-tyrosine phosphorylation showed that GAS inhibited the formation of phosphotyrosine proteins at the steps involving the engagement of integrin alphaIIbbeta3 and aggregation. However, GAS did not inhibit U46619-induced platelet shape change or the inhibitory effect of U46619 on the prostaglandin E1-evoked cyclic AMP level in GFP. It is concluded that GAS inhibits platelet response to TXA2 on the receptor-Gq-phospholipase Cbeta1 pathway, but not on the receptor-G1 pathway.