Inhibitory effects of thromboxane A(2) generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A(2) phosphorylation and arachidonic acid release

BACKGROUND: Thromboxane A(2) (TXA(2)) induces platelet aggregation and promotes thrombus formation. Although ginsenoside Ro (G-Ro) from Panax ginseng is known to exhibit a Ca(2+)-antagonistic antiplatelet effect, whether it inhibits Ca(2+)-dependent cytosolic phospholipase A(2) (cPLA(2α)) activity to prevent the release of arachidonic acid (AA), a TXA(2) precursor, is unknown. In this study, we attempted to identify the mechanism underlying G-Ro-mediated TXA(2) inhibition. METHODS: We investigated whether G-Ro attenuates TXA(2) production and its associated molecules, such as cyclooxygenase-1 (COX-1), TXA(2) synthase (TXAS), cPLA(2α), mitogen-activated protein kinases, and AA. To assay COX-1 and TXAS, we used microsomal fraction of platelets. RESULTS: G-Ro reduced TXA(2) production by inhibiting AA release. It acted by decreasing the phosphorylation of cPLA(2α), 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 TXA(2) production, which may counteract TXA(2)-associated thrombosis.