Differential effects of ganodermic acid S (cas 112430-63-4) on the thromboxane A2-signaling pathways in human platelets

Add time:07/23/2019    Source:sciencedirect.com

ganodermic acid S (cas 112430-63-4) (GAS) [lanosta-7,9(11),24-triene-3β,15α-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-9α,11α-methanoepoxyprostaglandin F2α), a thromboxane (TX) A2 mimetic. GAS at 2 μM inhibited 50% of cell aggregation. GAS at 7.5 μM inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of α-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 αIIbβ3 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 Cβ1 pathway, but not on the receptor-Gi pathway.

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