Inhibitory effect of the Korean herbal medicine, Dae-Jo-Whan, on platelet-activating factor-induced platelet aggregation

The anti-thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW) were investigated. Water extracts, a 70% methanol (MeOH) extract and an ethyl acetate (EtOAc) soluble fraction (III) from DJW inhibited platelet-activating factor (PAF)-induced platelet aggregation in vitro and in vivo assays. The extracts of DJW and eleven herbs from which it is derived, except for Panax ginseng Meyer, Angelica sinensis (OLIV.) DIELS and Schisandra chinensis Baill., inhibited AA-induced blood platelet aggregation to various extents. The effects observed with total DJW was synergistic over-additive rather that additive since the sum of single contributions was lower than the effect of the total extract. Fraction III was specially protected against the lethality of PAF, while verapamil did not afford any protection. Exogenously applied arachidonic acid (AA) (100 mu M) led to a 89% platelet aggregation, the release of 14 pmol of ATP, and the formation of either 225 pg of thromboxane A2 (TXA2) or 45 pg of prostaglandin E2 (PGE2), each parameter being related to 106 platelets. An application of DJW 5 min before AA, dose-dependently diminished aggregation, ATP-re lease, and the synthesis of TXA2 and PGE2, with IC50 values of 70, 87, 65 and 72 mu g/ml, respectively. The similarity of the IC50 values suggests the inhibition of cyclooxygenase (COX) by DJW as the primary target, thus suppressing the generation of TXA2, which induces platelet aggregation and the exocytosis of ATP by its binding on TXA2-receptors. These results indicate that DJW shows anti-thrombotic action on human platelets and inhibits the action of PAF in vivo by an antagonistic effect on PAR Therefore, it may be useful in treating disorders caused by PAR (c) 2005 Elsevier Ireland Ltd. All rights reserved.