The inhibitory mechanism of 6 traditional Chinese medicines on rabbit platelet aggregation in vitro, and the suppressive effect of oral administration of Toki-syakuyakusan on hyper-aggregability of the platelet from rabbit fed high cholesterol diet for 2 months, were investigated. Collagen-induced aggregation was inhibited by Keisi-bukuryogan, Kami-syoyo-san, Dai-saiko-to, Toki-syakuyaku-san, Hatimi-zio-gan and Syo-saiko-to in their lower concentrations than those inhibiting arachidonic acid- and thrombin-induced aggregation. These traditional Chinese medicines inhibited the release of [3H] arachidonic acid from membrane phospholipids by phospholipase A2, in [3H] arachidonic acid-labelled platelets under stimulation with collagen and thrombin in the concentration ranges that inhibited each aggregation. In their higher concentrations to inhibit arachidonic acid-induced aggregation, they suppressed the conversion of arachidonic acid to thromboxane A2 by about 50%. However, they had no effect on diacylglycerol formation induced by thrombin. The oral administration of Toki-syakuyaku-san depressed the increased aggregability of platelets from rabbit fed high cholesterol diet by 20-40% at the period of 1-2 months of feeding, without affecting plasma and platelet cholesterol level. These results indicate that the traditional Chinese medicines used here have an inhibitory effect on platelet phospholipase A2 activation, rather than on cyclooxygenase, and therefore inhibit platelet activation in vitro and ex vivo.
