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Triflavin, a potent aggregation inhibitor, purified from Trimeresurus flavoviridis snake venom
276
ABSTRACTS;
CHINESE-JAPANESE
SYMP. 1990
Vol. 63, No. 2
TRIFLAVIN, A POTENT AGGREGATION INHIBITOR, PURIFIED FROM TRIMERESURUS FLAVOVIRIDIS SNAKE VENOM T.F. HJ&ZW and J.R. Pharmacological Institute, college of Medicine, National Taiwan University, Taipei, Taiwan, ROC By means of gel filtrations, CM-Sephadex C-50 column and reverse-phase HPLC, a potent platelet aggregation inhibitor, was purified from Trimeresurus flavoviridis snake venom. It was a cysteine-rich single chain polypeptide, consisting of 71 amino acid residues with a molecular weight of 7,600 daltons. It inhibited aggregation of human platelets stimulated by ADP, epinephrine, thrombin, collagen and U46619, in preparations of platelet-rich plasma or washed platelet suspension (IC50, 50-80 nM) . Triflavin did not inhibit the intracellular mobilization of Qui 2-AM loaded platelets or affect the thromboxane B2 formation of platelets,stimulated by thrombin. Accordingly, Triflavin apparently did not inhibit the shape change and ATP release reaction of platelets stimulated by thrombin. Triflavin completely inhibited fibrinogen-induced aggregation of elastasetreated platelets (ICSO, 40 nM). In addition, it dose-dependently inhibited the binding of 1251-rhodostomin, which has been shown to be a specific binding ligand of the fibrinogen receptor of platelets, to ADP-stimulated platelets. In conclusion, Triflavin inhibits platelet aggregation by interferring with the fibrinogen binding to the activated platelets. It belongs to the trigraminlike peptides existing in snake venoms.
MECHANISMS OF THE ANTIPLATELET ACTIONS OF SOME COUMARIN DERIVATIVES ISOLATED FROM PLANT SOURCES C.M. Tena. H.L. J0i and *T.S. rdu Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, and *Department of Chemistry, National ChengKung Univ., Tainan, Taiwan, ROC Xanthyletin, xanthoxyletin, suberosin (from Citrus grandis), auraptene (from Severinia huxifolia) and poncitrin (from Poncitrus and characterized to be coumarin trifoliata) were isolated These coumarin compounds inhibited the aggregation derivatives. and ATP release of rabbit platelets induced by arachidonic acid, factor (PAF) and U46619 (a collagen, ADP, platelet-activating Thrombin-induced ATP release, thromboxane A2 receptor agonist). The antiplatelet actions but not the aggregation was inhibited. than that of compounds were more potent coumarin of these The thromboxane B2 formations in washed platelets dicumarol. caused by arachidonic acid, collagen and thrombin were suppressed. The phosphoinositides breakdown caused by collagen and PAF was They did not inhibit also inhibited by these coumarin compounds. fibrinogen-induced aggregation of elastase-treated platelets. It is concluded that the antiplatelet actions of these coumarin derivatives are due to the inhibition on thromboxane A2 formation and phosphoinositides breakdown.
ABSTRACTS;
CHINESE-JAPANESE
SYMP. 1990
Vol. 63, No. 2
TRIFLAVIN, A POTENT AGGREGATION INHIBITOR, PURIFIED FROM TRIMERESURUS FLAVOVIRIDIS SNAKE VENOM T.F. HJ&ZW and J.R. Pharmacological Institute, college of Medicine, National Taiwan University, Taipei, Taiwan, ROC By means of gel filtrations, CM-Sephadex C-50 column and reverse-phase HPLC, a potent platelet aggregation inhibitor, was purified from Trimeresurus flavoviridis snake venom. It was a cysteine-rich single chain polypeptide, consisting of 71 amino acid residues with a molecular weight of 7,600 daltons. It inhibited aggregation of human platelets stimulated by ADP, epinephrine, thrombin, collagen and U46619, in preparations of platelet-rich plasma or washed platelet suspension (IC50, 50-80 nM) . Triflavin did not inhibit the intracellular mobilization of Qui 2-AM loaded platelets or affect the thromboxane B2 formation of platelets,stimulated by thrombin. Accordingly, Triflavin apparently did not inhibit the shape change and ATP release reaction of platelets stimulated by thrombin. Triflavin completely inhibited fibrinogen-induced aggregation of elastasetreated platelets (ICSO, 40 nM). In addition, it dose-dependently inhibited the binding of 1251-rhodostomin, which has been shown to be a specific binding ligand of the fibrinogen receptor of platelets, to ADP-stimulated platelets. In conclusion, Triflavin inhibits platelet aggregation by interferring with the fibrinogen binding to the activated platelets. It belongs to the trigraminlike peptides existing in snake venoms.
MECHANISMS OF THE ANTIPLATELET ACTIONS OF SOME COUMARIN DERIVATIVES ISOLATED FROM PLANT SOURCES C.M. Tena. H.L. J0i and *T.S. rdu Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, and *Department of Chemistry, National ChengKung Univ., Tainan, Taiwan, ROC Xanthyletin, xanthoxyletin, suberosin (from Citrus grandis), auraptene (from Severinia huxifolia) and poncitrin (from Poncitrus and characterized to be coumarin trifoliata) were isolated These coumarin compounds inhibited the aggregation derivatives. and ATP release of rabbit platelets induced by arachidonic acid, factor (PAF) and U46619 (a collagen, ADP, platelet-activating Thrombin-induced ATP release, thromboxane A2 receptor agonist). The antiplatelet actions but not the aggregation was inhibited. than that of compounds were more potent coumarin of these The thromboxane B2 formations in washed platelets dicumarol. caused by arachidonic acid, collagen and thrombin were suppressed. The phosphoinositides breakdown caused by collagen and PAF was They did not inhibit also inhibited by these coumarin compounds. fibrinogen-induced aggregation of elastase-treated platelets. It is concluded that the antiplatelet actions of these coumarin derivatives are due to the inhibition on thromboxane A2 formation and phosphoinositides breakdown.