Biomedical subjects
Publications and source records attributed to F N Ko.
Panaxynol and ginsenosides Ro, Rg1, and Rg2 were found to be the main antiplatelet components in the diethyl ether and 1-butanol fractions, respectively, during the activity-guided fractionation of Panax ginseng, Panaxynol inhibited the aggregation, release reaction, and thromboxane formation in rabbit platelets while ginsenosides Ro, Rg1, and Rg2 suppressed the release reaction only.
Osthole, isolated from Chinese herb Angelica pubescens, inhibited platelet aggregation and ATP release induced by ADP, arachidonic acid, PAF, collagen, ionophore A23187 and thrombin in washed rabbit platelets. It showed a weak activity in platelet-rich plasma. Osthole inhibited the thromboxane B2 formation caused by arachidonic acid, collagen, ionophore A23187 and thrombin in washed platelets, and also the thromboxane B2 formation caused by the incubation of lysed platelet homogenate with arachidonic acid. The generation of inositol phosphates in washed platelets caused by collagen, PAF and thrombin was suppressed by osthole. These data indicate that the inhibitory effect of osthole on platelet aggregation and release reaction was due to the inhibition of thromboxane formation and phosphoinositides breakdown.
Xanthones and their glycosides were tested for their antiplatelet activities in washed rabbit platelets. Tripteroside acetate and norathyriol acetate were the most potent inhibitors. Tripteroside acetate inhibited platelet aggregation and ATP release induced by ADP, arachidonic acid, platelet-activating factor (PAF), collagen, ionophore A23187 and thrombin. The IC50 values of tripteroside acetate toward arachidonic acid- (100 microM) and collagen- (10 micrograms/ml) induced platelet aggregation were 10 and 30 micrograms/ml respectively. It inhibited thromboxane B2 formation of washed platelets caused by arachidonic acid, collagen, thrombin and ionophore A23187 and also that caused by the incubation of lysed platelet homogenate with arachidonic acid. Tripteroside acetate decreased the formation of inositolphosphate caused by thrombin, collagen and PAF, whereas it had no direct effect on fibrinogen-platelet interaction. It is concluded that xanthone derivatives inhibited platelet aggregation and release reaction by diminishing thromboxane formation and phosphoinositide breakdown.
Protopine inhibited the aggregation and ATP release of rabbit platelets induced by ADP, arachidonic acid, PAF, collagen and ionophore A23187. Although the platelet aggregation caused by thrombin was not inhibited by protopine (100 micrograms/ml), the release reaction was partially suppressed. In rabbit platelet-rich plasma, protopine also inhibited the platelet aggregation caused by ADP, arachidonic acid, PAF and collagen. The thromboxane B2 formation of washed platelets caused by arachidonic acid, collagen, ionophore A23187 and thrombin was suppressed by protopine. Protopine inhibited the intracellular calcium increase caused by arachidonic acid in quin-2/AM loaded rabbit platelets. In the presence of indomethacin, the intracellular calcium increase caused by collagen and PAF was completely suppressed by protopine, and the intracellular calcium increase caused by thrombin was partially inhibited. The phosphoinositides breakdown caused by collagen and PAF was inhibited by protopine, but that by thrombin was not affected significantly. Protopine did not cause the elevation of cyclic AMP level of platelets. It is concluded that the antiplatelet effects of protopine is due to inhibition on thromboxane formation and phosphoinositides breakdown and then lead to the decrease of intracellular calcium concentration.
The antiplatelet effect of panaxynol isolated from the diethyl ether layer was compared with those of ginsenosides from the butanol layer of Panax ginseng. Panaxynol (0.1 mg/ml) inhibited markedly the aggregation of washed platelets induced by collagen, arachidonic acid, ADP, ionophore A23187, PAF and thrombin while ginsenosides had no significant effect on the aggregation but ginsenoside Ro (1 mg/ml) inhibited the ATP release of platelets. Less inhibitory effect of panaxynol was observed in the aggregation of platelet-rich plasma. Thromboxane B2 formation of platelets was inhibited by panaxynol but not by ginsenosides. The antiplatelet effect of panaxynol was dependent on the incubation time and the aggregability of platelets inhibited by panaxynol could not easily be recovered after washing the platelets. In human platelet-rich plasma, panaxynol prevented secondary aggregation and completely blocked ATP release from platelets induced by epinephrine and ADP. Both panaxynol and ginsenoside Rg2 inhibited the rise of intracellular calcium caused by collagen. It is concluded that panaxynol is the most potent antiplatelet agent in ginseng and its mechanism of action is chiefly due to the inhibition of thromboxane formation.
Magnolol and honokiol are two position isomers isolated from the bark of Magnolia officinalis. Both inhibited the aggregation and ATP release of rabbit platelet-rich plasma induced by collagen and arachidonic acid without affecting that induced by ADP, PAF or thrombin. Aggregation of washed platelets was more markedly inhibited than that of platelet-rich plasma, while the aggregation of whole blood was least affected by both inhibitors. Thromboxane B2 formation caused by collagen, arachidonic acid or thrombin was in each case inhibited by magnolol and honokiol. The rise of intracellular calcium caused by arachidonic acid or collagen was also suppressed by both agents. Collagen-induced intracellular calcium increase in the presence of indomethacin was suppressed by magnolol. It is concluded that the antiplatelet effect of magnolol and honokiol is due to an inhibitory effect on thromboxane formation and also an inhibition of intracellular calcium mobilization.
Platelet aggregation induced by three thrombin-like enzymes of snake venoms was compared with that by thrombin. Acutin was isolated from Agkistrodon acutus venom and thrombocytin and batroxobin were from Bothrops atrox venom. The fibrinogen-clotting activities were 700, 170 and 7 U/mg for batroxobin, acutin and thrombocytin, respectively. They induced aggregation and ATP release of washed rabbit platelets. The aggregating activity of thrombin was 10(2), 10(4) and 10(5) times more potent than those of thrombocytin, acutin and batroxobin, respectively. Platelet-activating potency of the thrombin-like enzymes was correlated with their effectiveness on the retractility and elasticity of the clots. Platelet aggregation induced by thrombin or thrombocytin could be inhibited by heparin with antithrombin III while that by acutin or batroxobin could not. Indomethacin showed weak inhibition on the aggregation while the ADP-scavenging system, creatine phosphate/creatine phosphokinase, inhibited the aggregation induced by the three thrombin-like enzymes but not that by thrombin. Platelet aggregation induced by the thrombin-like enzymes could not be inhibited by PAF antagonists-BN 52021, kadsurenone or L-652,731. In the presence of EGTA, only thrombin could induce ATP release from platelets. Thrombin-like enzymes and low concentration of thrombin did not form thromboxane B2. Nitroprusside and prostaglandin E1 completely inhibited the aggregation, mepacrine and imipramine showed marked inhibition while verapamil had only weak inhibition. It is concluded that the aggregation induced by the thrombin-like enzymes is different from that of thrombin and mainly due to ADP released from platelets.