CHARACTERIZATION OF THE ANTIPLATELET EFFECTS OF (2S)-5-METHOXY-6-METHYLFLAVAN-7-OL FROM DRACONIS RESINA

(2S)-5-methoxy-6-methylflavan-7-ol (MMF) was purified from Draconis Re sina and its in vitro effects on various aspects of platelet reactivit y were examined. Results indicated that MMF dose dependently inhibited aggregation of washed rabbit platelets induced by collagen, arachidon ic acid, ADP, U46619 or platelet-activating factor (PAF), with IC50 va lues of 17.2, 49.8, 179.8, 109.6, and 189.2 mu M, respectively. Concom itantly, MMF also dose dependently suppressed ATP release by platelets activated by these stimulants. The increase in intracellular free cal cium ([Ca2+](i)), elicited by these activating agents, was inhibited b y MMF as reflected by fura-2 fluorescence measurements. However, MMF h ad no effects on the cyclic AMP level of platelets. In addition, MMF i nhibited the arachidonic acid-induced thromboxane B-2 and prostaglandi n D-2 formation in intact platelet suspensions or homogenized platelet lysates. This study provided evidence that MMF is an antiplatelet age nt whose activity is likely related to cyclooxygenase inhibition and s uppression of[Ca2+](i) increase. (C) 1998 Elsevier Science B.V.