Inhibitory effects of thromboxane A2 generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A2 phosphorylation and arachidonic acid release

摘要

Background Thromboxane Asub2/sub (TXAsub2/sub) induces platelet aggregation and promotes thrombus formation. Although ginsenoside Ro (G-Ro) from Panax ginseng is known to exhibit a Casup2+/sup-antagonistic antiplatelet effect, whether it inhibits Casup2+/sup-dependent cytosolic phospholipase Asub2/sub (cPLAsub2α/sub) activity to prevent the release of arachidonic acid (AA), a TXAsub2/sub precursor, is unknown. In this study, we attempted to identify the mechanism underlying G-Ro-mediated TXAsub2/sub inhibition. Methods We investigated whether G-Ro attenuates TXAsub2/sub production and its associated molecules, such as cyclooxygenase-1 (COX-1), TXAsub2/sub synthase (TXAS), cPLAsub2α/sub, mitogen-activated protein kinases, and AA. To assay COX-1 and TXAS, we used microsomal fraction of platelets. Results G-Ro reduced TXAsub2/sub production by inhibiting AA release. It acted by decreasing the phosphorylation of cPLAsub2α/sub, p38-mitogen-activated protein kinase, and c-Jun N-terminal kinase1, rather than by inhibiting COX-1 and TXAS in thrombin-activated human platelets. Conclusion G-Ro inhibits AA release to attenuate TXAsub2/sub production, which may counteract TXAsub2/sub-associated thrombosis.