Biomedical subjects

C M Teng

Publications and source records attributed to C M Teng.

At least 163 records · Page 9Linked to original sources

PubMed1993

Trimucytin: a collagen-like aggregating inducer isolated from Trimeresurus mucrosquamatus snake venom.

Trimucytin is a potent platelet aggregation inducer isolated from Trimeresurus mucrosquamatus snake venom. Similar to collagen, trimucytin has a run of (Gly-Pro-X) repeats at the N-terminal amino acids sequence. It induced platelet aggregation, ATP release and thromboxane formation in rabbit platelets in a concentration-dependent manner. The aggregation was not due to released ADP since it was not suppressed by creatine phosphate/creatine phosphokinase. It was not either due to thromboxane A2 formation because indomethacin and BW755C did not have any effect on the aggregation even thromboxane B2 formation was completely abolished by indomethacin. Platelet-activating factor (PAF) was not involved in the aggregation since a PAF antagonist, kadsurenone, did not affect. However, RGD-containing peptide triflavin inhibited the aggregation, but not the release of ATP, of platelets induced by trimucytin. Indomethacin, mepacrine, prostaglandin E1 and tetracaine inhibited the thromboxane B2 formation of platelets caused by collagen and trimucytin. Forskolin and sodium nitroprusside inhibited both platelet aggregation and ATP release, but not the shape change induced by trimucytin. In quin-2 loaded platelets, the rise of intracellular calcium concentration caused by trimucytin was decreased by 12-O-tetradecanoyl phorbol-13 acetate, imipramine, TMB-8 and indomethacin. In the absence of extracellular calcium, both collagen and trimucytin caused no thromboxane B2 formation, but still induced ATP release which was completely blocked by R 59022. Inositol phosphate formation in platelets was markedly enhanced by trimucytin and collagen. MAB1988, an antibody against platelet membrane glycoprotein Ia, inhibited trimucytin- and collagen-induced platelet aggregation and ATP release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1993

Antiplatelet activity of some prenylflavonoids.

Eight naturally occurring prenylflavonoids were tested for their antiplatelet activities in rabbit platelet suspension. Cyclomorusin and artomunoxanthone showed strong inhibition of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) induced platelet aggregation. Cyclomulberrin, dihydroisocycloartomunin, cyclocommunol and cyclocommunin showed strong inhibition of arachidonic acid (AA)- and collagen-induced platelet aggregation. Cyclomorusin also inhibited markedly collagen-induced platelet aggregation. Cyclocommunin, dihydroisocycloartomunin and cyclomulberrin also showed slight but significant antiplatelet effects on the aggregation induced by PAF. Of the compounds tested, cyclocommunin exhibited the most potent inhibition of platelet aggregation induced by collagen (IC50 = 14.4 microM) and AA (IC50 = 12.5 microM). Thromboxane B2 formation caused by AA was suppressed by cyclocommunin and artomunoxanthone.

Animals↗

PubMed1993

CIS-19, a novel platelet activating factor receptor antagonist: in vitro and in vivo studies.

The effects of CIS-19 (cis-2-(3,4-dimethoxyphenyl)-6-isopropoxy-7-methoxyl-1-(N-methylforma mido)-1,2, 3,4-tetrahydronaphthalene) was determined in vitro in rabbit platelets and in vivo in rats and guinea-pigs. CIS-19 inhibited in a selective and concentration-dependent manner the aggregation and ATP release reaction of rabbit platelets induced by PAF (4 nM). The IC50 values of CIS-19 on PAF-induced aggregation of washed platelets and platelet-rich plasma were 11.3 +/- 2.7 and 16.8 +/- 3.0 microM respectively. BN52021 also inhibited PAF-induced aggregation of washed platelets with an IC50 value of 11.7 +/- 2.8 microM. CIS-19 inhibited [3H]PAF (4 nM) binding to washed rabbit platelets with an IC50 value of 1.5 +/- 0.2 microM. The concentration-response curve of PAF-induced aggregation of washed platelets was shifted rightwards by CIS-19 with pA2 and pA10 values of 7.1 (6.8-7.3 for 95% confidence limit) and 6.1 (5.8-6.2) respectively. The thromboxane B2 formation of washed platelets caused by AA, collagen or thrombin was not affected by CIS-19 of concentrations below 400 microM. CIS-19 (25 microM) completely blocked PAF-induced, but not collagen- or thrombin-induced [3H]inositol monophosphate formation of washed platelets. When CIS-19 (2.5 and 5 mg/kg) was injected i.v. into the femoral vein, it did not affect the blood pressure of rats, but antagonized PAF (2.5 micrograms/kg, i.v.)-induced hypotensive shock either preventively or curatively. CIS-19 (2.5 and 5 mg/kg) also blocked PAF (50 ng/kg)-induced, but not AA (50 micrograms/kg)-induced, bronchoconstriction in guinea-pigs. It is concluded that CIS-19 is an effective PAF receptor antagonist not only in vitro, but also in vivo.

Adenosine Triphosphate↗

PubMed1993

gamma-Pyrone compounds. IV: Synthesis and antiplatelet effects of mono- and dioxygenated xanthones and xanthonoxypropanolamine.

Xanthodilol, mono- and dioxygenated xanthones, and 1,3-, 2,3-, 3,4-, 3,5-, 1,6-, 2,6- and 3,6-dioxygenated xanthones were synthesized from benzophenone precursors by Friedel-Crafts acylation and subsequent base-catalyzed cyclization to eliminate methanol. 3-Hydroxy-xanthone, xanthodilol, 2,3-dihydroxyxanthone diacetate, and 3,4-dihydroxyxanthone and its diacetate showed potent antiplatelet effects on arachidonate- and collagen-induced aggregation. 3,5-Dihydroxyxanthone and its diacetate, 1,6-dimethoxyxanthone, and 3,6-dihydroxyxanthone and its diacetate showed potent antiplatelet effects on arachidonate-induced aggregation.

Adenosine Diphosphate↗

PubMed1993

The inhibitory effect of magnolol on cutaneous permeability in mice is probably mediated by a nonselective vascular hyporeactivity to mediators.

In the present study, we demonstrated the inhibitory effect of magnolol on the plasma leakage in passive cutaneous anaphylactic (PCA) reaction, neurogenic inflammation, dorsal skin and ear edema in mice. Hind-paw skin plasma extravasation caused by antidromic stimulation of the saphenous nerve was reduced in mice pretreated with magnolol, diphenydramine or methysergide, but not with indomethacin. Ear edema formation in the PCA reaction was reduced by magnolol in dose-dependent manner. In addition, histamine-, serotonin-, compound 48/80-, bradykinin- and substance P-induced ear edema in mice was also suppressed by magnolol. A dose- and time-dependency of the inhibitory effect of magnolol was demonstrated in histamine- and compound 48/80-induced dorsal skin edema. The maximal inhibitory effect produced by a single dose of magnolol (10 mg/kg) persisted for 1 h, and significant suppression lasted for at least 3 h. In compound 48/80-pretreated mice, the histamine content of the ear was greatly reduced. Bradykinin- and substance P-induced ear edema in compound 48/80-pretreated mice was less severe than that seen in normal mice, but was still significantly reduced by magnolol pretreatment. Moreover, the inhibitory effect of magnolol was more marked than that of diphenhydramine combined with methysergide. These results suggest that the inhibitory effect of magnolol on local edema formation probably occurs through a nonselective inhibition on vascular tissue to prevent the permeability change caused by various mediators.

Adrenalectomy↗

PubMed1993

Antiplatelet effects and vasorelaxing action of some constituents of Formosan plants.

Various xanthones as well as quercetin have been shown to exhibit antiplatelet activity. A series of anthraquinones analogues structurally related to xanthones and a series of quercetin-related compounds were tested for their antiplatelet effects. Emodin, frangulin B, kaempferol tetraacetate, quercetin-3-O-galactoside octaacetate, rhamnazin triacetate, and rhamnetin tetraacetate were found to be potent antiplatelet agents, and 1,8-dihydroxy-6-methoxy-3-methylanthraquinone 8-O-rhamnosyl-(1-->2)-glucoside, rhamnustrioside undecaacetate, rutin decaacetate, and quercetin-3-O-(6-O-alpha-L-arabinopyranosyl)-beta-D-galactopyranos ide decaacetate showed significant antiplatelet effects. Quercetin showed vasorelaxing action in rat thoracic aorta.

Animals↗

PubMed1993

Inhibition of platelet aggregation by shikonin derivatives isolated from Arnebia euchroma.

Four antiplatelet components were isolated from Arnebia euchroma. They inhibited the aggregation of washed rabbit platelets caused by collagen, arachidonic acid, platelet-activating factor, ADP, or thrombin. The potency of inhibiting collagen-induced platelet aggregation is in the following order: acetylshikonin (IC50 = 2.1 microM), teracrylshikonin (2.8 microM), beta, beta-dimethylacrylshikonin (4.2 microM), and shikonin (10.7 microM). In rat aorta, acetylshikonin and shikonin inhibited high potassium and norepinephrine-induced contractions, while beta, beta-dimethylacrylshikonin and teracrylshikonin potentiated the phasic contraction caused by norepinephrine.

Animals↗

PubMed1993

Triflavin, an Arg-Gly-Asp-containing peptide, inhibits tumor cell-induced platelet aggregation.

In this study, we examined the effect of triflavin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, on human cervical carcinoma (HeLa) cell- and B16-F10 mouse melanoma cell-induced platelet aggregation (TCIPA) in heparinized platelet-rich plasma. TCIPA appears to play an important role in the development of certain experimental tumor metastases. Two ADP-scavenging agents, apyrase (10 U/ml) and creatine phosphate (CP) (5 mM)/creatine phosphokinase (CPK) (5 U/ml) completely inhibited B16-F10 TCIPA, but hirudin (5 U/ml) had no effect. In contrast, apyrase and CP/CPK did not inhibit HeLa TCIPA while hirudin completely inhibited it. Furthermore, HeLa cells initially induced platelet aggregation and then blood coagulation at a later stage. In addition, HeLa cells shortened, in a concentration-dependent manner, the recalcification time of normal as well as factor VIII- and IX-deficient human plasma, but did not affect the recalcification time of factor VII-deficient plasma. This suggests that HeLa TCIPA occurs via activation of the extrinsic pathway, probably owing to tumor cell expression of tissue factor-like activity. HeLa cell-induced thrombin generation was confirmed by detection of amidolytic activity towards a chromogenic substrate, S-2238 (H-D-Phe-Pip-Arg-p-NA). Triflavin and GRGDS inhibited, in a dose-dependent manner, TCIPA caused by either cell line. On a molar basis, triflavin was 10,000-30,000 times more potent than GRGDS in this regard. Moreover, monoclonal antibodies raised against glycoprotein (GP) IIb/IIIa complex (i.e., 7E3 and AP2) and against GP Ib (i.e., AP1) completely inhibited HeLa TCIPA. 7E3 and AP2 inhibited B16-F10 TCIPA by up to 80% whereas AP1 showed only 30% inhibition of B16-F10 TCIPA. In conclusion, the inhibitory effect of triflavin on HeLa and B16-F10 TCIPA may be mediated principally by the binding of triflavin to the fibrinogen receptor associated with GP IIb/IIIa complex on the platelet surface. However, GP Ib is also involved in HeLa TCIPA as thrombin formation is the key factor in triggering platelet aggregation caused by HeLa cells.

Animals↗

PubMed1993

Effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity in hyperlipidaemic rats.

1. The effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity were investigated in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats, fed a high fat-high cholesterol diet. 2. In high fat-high cholesterol (HF-HC) diet fed WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) for 4 weeks caused significant reductions in total plasma cholesterol (CE) by reducing the low density lipoprotein (LDL) fraction, and reductions in total plasma triglyceride (TG) by reducing the very low density lipoprotein (VLDL) fraction. 3. Dicentrine therapy was associated with increased high density lipoprotein (HDL)-cholesterol levels; thus the ratio of total plasma cholesterol to HDL-cholesterol was improved. 4. In HF-HC diet fed conscious WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) also evoked dose-related decreases in mean arterial pressure (MAP) which were of greater magnitude in SH rats. Neither dose of dicentrine caused a significant change in heart rate (HR). 5. The aortic arches from SH rats fed the HF-HC diet for 8 weeks were significantly more affected by the atherosclerotic lesions than the abdominal aortae and renal arteries of WKY and SH rats. Oral administration of dicentrine (5 and 10 mg kg-1) for 4 weeks did not diminish the atherosclerotic lesion areas in WKY and SH rats. 6. In aortae of the hyperlipidaemic rats, significantly attenuated EC50 values and augmented maximal responses for phenylephrine-induced contraction were obtained. Endothelium-dependent relaxation to acetylcholine was abolished, while endothelium-independent relaxation to nitroprusside was well preserved. Dicentrine therapy caused significantly augmented EC50 values and attenuated maximal responses for phenylephrine-induced contraction in hyperlipidaemic rats. However, dicentrine neither prevented the impaired relaxation to acetylcholine, nor affected the relaxation to nitroprusside during atherosclerosis progression.7. It is concluded that dicentrine decreases MAP, plasma CE, LDL-CE, plasma TG, VLDL-TG,vascular hyperreactivity to phenylephrine and increases HDL-CE levels. Dicentrine may thus hold potential for the reduction of two of the major risk factors, hypertension and hyperlipidaemia, for cardiovascular disease.

Animals↗

PubMed1993

Pharmacological activity of (-)-discretamine, a novel vascular alpha-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens.

1. The pharmacological activity of (-)-discretamine, isolated from Fissistigma glaucescens, was determined in rat isolated thoracic aorta, cardiac tissues and ventricular myocytes and guinea-pig isolated trachea. 2. (-)-Discretamine was found to be an alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline (pA2 = 7.20 +/- 0.10)- or phenylephrine (pA2 = 7.60 +/- 0.09)-induced vasoconstriction. It was as potent as phentolamine (pA2 = 7.51 +/- 0.10), but was more potent than yohimbine (pA2 = 6.18 +/- 0.06). Removal of endothelium significantly increased the antagonistic potency of (-)-discretamine on noradrenaline (pA2 = 7.52 +/- 0.09)- or phenylephrine (pA2 = 7.90 +/- 0.09)-induced vasoconstriction. 3. (-)-Discretamine was also an alpha 2-adrenoceptor blocking agent (pA2 = 6.30 +/- 0.15) and a 5-hydroxytryptamine antagonist (pA2 = 6.87 +/- 0.06), both in rat aorta denuded of endothelium. 4. (-)-Discretamine protected alpha-adrenoceptors from alkylation by the irreversible blocking agent, phenoxybenzamine. 5. [3H]-inositol monophosphate formation caused by noradrenaline (3 microM) in rat thoracic aorta was suppressed by (-)-discretamine (10 and 30 microM) and prazosin (3 microM). 6. A high concentration of (-)-discretamine (30 microM) did not affect the contraction induced by the thromboxane receptor agonist U-46619, prostaglandin F2 alpha (PGF2 alpha), angiotensin II, high K+ or endothelin in rat aorta denuded of endothelium. Neither cyclic AMP nor cyclic GMP content of rat thoracic aorta was changed by (-)-discretamine. 7. Contraction of guinea-pig trachea caused by histamine, leukotriene C4 or carbachol was not affected by (-)-discretamine (30 microM). (-)-Discretamine also did not block beta l- or beta2-adrenoceptor-mediated responses induced by isoprenaline in rat right atria and guinea-pig trachea.8. A voltage clamp study in rat ventricular single myocytes revealed that sodium inward current, slow inward Ca2+ current or transient (ItO) and steady state (I800) outward current was not affected by(-)-discretamine (30 microM).9. It is concluded that (-)-discretamine is a selective x-adrenoceptor and 5-HT receptor antagonist in vascular smooth muscle.

Adrenergic alpha-Antagonists↗

PubMed1993

Ca(2+)-channel blockade in rat thoracic aorta by crychine isolated from Cryptocarya chinensis Hemsl.

The pharmacological effects of crychine, isolated from Cryptocarya chinensis Hemsl, on rat thoracic aorta were examined. In the high-K+ medium (60 mM), Ca2+ (0.03-3 mM)-induced vasoconstriction was inhibited by crychine in a concentration-dependent manner (10-100 micrograms mL-1). Increasing the incubation time from 5 to 30 min did not cause more pronounced inhibitory effect on KCl-induced contraction. The tonic contractions elicited by KCl (60 mM) and Bay K 8644 (0.1 microM) were also relaxed by the addition of crychine and were more marked in the 1.9 mM than in the 5 mM Ca2+ medium. The noradrenaline concentration-response curves were antagonized non-competitively by crychine (10-100 micrograms mL-1). At the plateau of noradrenaline-induced tonic contraction, the addition of crychine also caused relaxation. This relaxing effect of crychine was not antagonized by indomethacin (20 microM) or methylene blue (50 microM), and was still present in denuded aorta or in the presence of nifedipine (2 microM). Caffeine (10 mM)-induced contraction and cAMP or cGMP levels were not affected by crychine. It is concluded that crychine relaxes the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1993

Combined use of aspirin and heparin inhibits in vivo acute carotid thrombosis.

BACKGROUND AND PURPOSE: Carotid atherosclerotic thrombosis is an important cause of ischemic stroke in Western countries. The therapeutic efficacy of either aspirin or heparin alone in this setting is still controversial. Recently we developed a simple model, the "clamp" method, to induce acute carotid mural thrombosis in vivo in guinea pigs. In this study, we used this model to evaluate the antithrombotic effects of aspirin, heparin, and their combination. METHODS: Sixty-four male guinea pigs were divided equally into control, aspirin, heparin, and combined groups. Physiological saline, aspirin (5 mg/kg body wt), heparin (200 units/kg body wt), or a combination of aspirin and heparin, respectively, was injected via the jugular vein before the use of the clamp method. Thirty minutes after the injection of saline or drug(s), Péan's forceps was used to clamp the carotid artery at a tangent angle for 3 minutes. One hour later, the carotid artery was resected and prepared for observation under a scanning electron microscope or light microscope to evaluate the degree of mural thrombosis. RESULTS: The results showed that the combination of aspirin and heparin had an excellent effect in inhibiting in vivo acute carotid thrombosis (p < 0.001) and was significantly better than the effect of aspirin alone (p < 0.01) or heparin alone (p < 0.01). CONCLUSIONS: Our study clearly demonstrated that the combined use of aspirin and heparin produced a much better antithrombotic effect than either agent alone at sites of carotid endothelial injury when given before the injury. This combined regimen may be useful clinically in acute carotid thrombosis secondary to carotid diseases or carotid endarterectomy.

Animals↗

PubMed1992

A novel alpha-type fibrinogenase from Agkistrodon rhodostoma snake venom.

By means of CM-Sephadex C-50 column chromatography, gel-filtration on sephadex G-75 and Sephacryl S-200 columns, a purified fibrinogenase, kistomin, was obtained from venom of Agkistrodon rhodostoma. It was a single peptide-chain with a molecular mass of about 21,800 Da containing about 202 amino-acid residues as revealed by amino acid analysis. Kistomin preferentially cleaved A alpha- and subsequently the gamma-chain of fibrinogen, leaving the B beta-chain unaffected. Its fibrinogenolytic activity was estimated to be 36.6 +/- 4.5 mg/min per mg protein and was inhibited by the pretreatment of EDTA, suggesting that it is a metalloproteinase. Its fibrinogenolytic activity in platelet-poor plasma is much less potent as compared to that in purified fibrinogen solution. It inhibited ristocetin-induced aggregation of human platelets in a dose-dependent manner in the presence of von Willebrand factor.

Amino Acids↗

PubMed1992

Triflavin, an RGD-containing antiplatelet peptide, binds to GpIIIa of ADP-stimulated platelets.

Triflavin, an Arg-Gly-Asp-containing snake venom peptide, inhibits platelet aggregation through the blockade of fibrinogen binding to the activated platelets. It binds to fibrinogen receptors associated with the glycoprotein IIb/IIIa complex with a Kd value of 7 x 10(-8) M. In this report, a chemical cross-linking approach was used to further characterize the binding components of triflavin on platelet membrane. 125I-triflavin binding was performed with the aid of a chemical cross-linking reagent, DTSSP. Analysis of the cross-linked products by SDS-PAGE (7.5% gel) and subsequent autoradiogram revealed that 125I-triflavin was cross-linked specifically to a protein with an apparent molecular weight of 1.1 x 10(5), and this reaction was inhibited by GRGDS and excess of non-labeled triflavin. This 110 KDa component was identified to be GpIIIa, recognized by AP3, a mAb against GpIIIa, by immunoblotting technique. These results indicate that the triflavin-binding sites on platelets reside at a site in close proximity to GpIIIa.

Adenosine Diphosphate↗

PubMed1992

Vasorelaxation of rat thoracic aorta caused by osthole isolated from Angelica pubescens.

The pharmacological effects of osthole on isolated rat thoracic aorta were examined. Osthole inhibited norepinephrine (NE, 3 microM)-induced phasic and tonic contractions in rat thoracic aorta in a concentration-dependent manner (40-200 microM). The tonic contraction elicited by NE was also relaxed by the addition of osthole. This relaxing effect of osthole was not affected by indomethacin (20 microM) and was still observed in endothelium-denuded rat aorta. Methylene blue (50 microM) partially antagonized this relaxing effect of osthole. In high-K+ medium (80 mM), the Ca2+ (0.03-3 mM)-induced vasocontraction was inhibited concentration dependently by osthole (20-100 microM). Addition of osthole (100 microM) at the plateau of the K+ (80 mM)-induced contraction caused relaxation. Methylene blue (50 microM) did not antagonize this relaxation. In Ca(2+)-free medium, the caffeine (10 mM)-induced phasic contraction was also suppressed by osthole in a concentration-dependent manner. Although the cAMP level was not changed by osthole, the cGMP level of rat aorta was increased by osthole in a concentration-dependent manner. The increase in cGMP level caused by osthole was completely blocked by methylene blue. [3H]Inositol monophosphate formation caused by NE was not affected by osthole at a concentration of 200 microM. The 45Ca2+ influx elicited by either NE or high K+ was inhibited by osthole in a concentration-dependent manner. It is concluded that osthole relaxes rat thoracic aorta by virtue of its Ca(2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle.

Animals↗

PubMed1992

PAF antagonism in vitro and in vivo by aglafoline from Aglaia elliptifolia Merr.

Aglafoline, isolated from Aglaia elliptifolia Merr, inhibited in a selective and concentration-dependent manner the aggregation and ATP release reaction induced in washed rabbit platelets by PAF (platelet-activating factor). The IC50 values of aglafoline, BN52021 and kadsurenone on PAF (3.6 nM)-induced platelet aggregation were about 50, 12 and 18 microM, respectively. Aglafoline also inhibited [3H]PAF (3.6 nM) binding to washed rabbit platelets with an IC50 value of 17.8 +/- 2.6 microM. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by aglafoline with pA2 and pA10 values of 5.97 and 5.04, respectively. Although thromboxane B2 formation caused by collagen and thrombin was partially suppressed by aglafoline, thromboxane B2 formation caused by ionophore A23187 and arachidonic acid was not affected. Aglafoline inhibited the [3H]inositol monophosphate formation caused by PAF but not that caused by collagen or thrombin in the presence of indomethacin (20 microM). The cAMP content of washed rabbit platelets was not affected by aglafoline. Rat femoral intravenous administration of aglafoline (10 mg/kg) did not affect blood pressure. However, aglafoline (10 mg/kg) both prophylactically and therapeutically antagonized PAF (2.5 micrograms/kg)-induced hypotensive shock in rats. Intravenous PAF (30 ng/kg) caused severe bronchoconstriction in guinea pigs. This effect was completely blocked by aglafoline. This implies aglafoline is an effective PAF antagonist not only in vitro, but also in vivo.

Adenosine Triphosphate↗

PubMed1992

Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line.

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5 U/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on s-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC50, 0.02 microM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC50, 0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E3 and 10 E5) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.

Amino Acid Sequence↗

PubMed1992

Antiplatelet actions of some coumarin compounds isolated from plant sources.

Xanthyletin, xanthoxyletin, suberosin (all from Citrus grandis), aurapten (from Severinia huxifolia) and poncitrin (from Poncirus trifoliata) were isolated and their chemical structures were characterized to be coumarin compounds. All these coumarin compounds except xanthyletin inhibited the aggregation and ATP release of rabbit platelets induced by arachidonic acid, collagen, ADP, platelet-activating factor (PAF) or U46619 (a thromboxane A2 analog). Thrombin-induced ATP release, but not the aggregation, was also inhibited by these compounds. Xanthyletin inhibited only platelet aggregation induced by arachidonic acid and collagen, while poncitrin inhibited that caused by PAF more markedly than other coumarin compounds. The thromboxane B2 formation in washed platelets caused by arachidonic acid and collagen was suppressed by these coumarin compounds. The phosphoinositide breakdown caused by collagen and PAF was also inhibited by these compounds. They did not affect fibrinogen-induced aggregation of elastase-treated platelets. These antiplatelet actions were immediate, reversible by washout and independent on the incubation time (except suberosin). Antiaggregating effect was also studied by an electrical impedance method and the inhibitory effect of coumarin compounds on the whole blood and platelet-rich plasma was much less than that of platelet suspension in the aggregation induced by collagen, PAF and ADP. It is concluded that the antiplatelet actions of these coumarin compounds are due to the inhibition on thromboxane A2 formation and phosphoinositides breakdown.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗