Anti-platelet effects of bioactive compounds isolated from the bark of Rhus verniciflua Stokes

It has previously been shown that EtOAc extracts of Rhus verniciflua Stokes (RVS) inhibit the platelet aggregation response. In this report, bioassay-guided fractionation using ADP-, arachidonic acid-, and collagen-induced human platelet aggregation by a whole blood aggregometer yielded the bioactive compounds isomaltol and pentagalloyl glucose from different highly effective fractions. In addition, column chromatography of fractions from RVS yielded another five compounds: butin, fisetin, sulfuretin, butein and 3,4′,7,8-tetrahydroxyflavone. We investigated the effects of bioactive compounds from RVS fractions on several markers of platelet activation using receptor expression on platelet membranes, including glycoprotein IIb/IIIa (CD41), GPIIb/IIIa-like expression (PAC-1) and P-selectin (CD62), and intracelluar calcium mobilization responses by flow cytometry in healthy subjects. Dose-dependent inhibition of platelet aggregation and significantly decreased platelet activation were observed for the isomaltol- and pentagalloyl glucose-treated platelets, respectively. These results show that isomaltol and pentagalloyl glucose from the bark of Rhus verniciflua Stokes have potent anti-platelet activity and emphasize the need to further examine the mechanism of these active compounds for platelet modulation.