Biomedical subjects

C M Teng

Publications and source records attributed to C M Teng.

At least 73 records · Page 4Linked to original sources

PubMed1998

Effect of PP1D-1, a synthetic antiplatelet compound, on rabbit platelets.

The antiplatelet mechanism of a synthetic compound, 2-chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D-1), was studied by employing washed rabbit platelets in vitro. PP1D-1 concentration-dependently inhibited thrombin (0.1 U/ml)-, platelet-activating factor (2 ng/ml)-, collagen (10 microg/ml)-, arachidonic acid (100 microM)- and U46619 (1 microM)-induced aggregation and ATP release in washed rabbit platelets. The IC50 values of PP1D-1 for aggregation induced by the above inducers are 17.9+/-1.7, 9.8+/-1.1, 3.9+/-0.4, 1.8+/-0.3 and 1.7+/-0.3 microM, respectively. PP1D-1 did not affect platelet thromboxane B2 or prostaglandin D2 formation induced by arachidonic acid, indicating that it did not affect cyclooxygenase and thromboxane synthase activities. PP1D-1 significantly inhibited the formation of inositol 1,4,5-trisphosphate caused by these five platelet stimulators. Moreover, PP1D-1 inhibited the increase in intracellular calcium concentration induced by these agents. On the contrary, PP1D-1 did not inhibit thapsigargin-elevated intracellular calcium concentration in indomethacin-pretreated platelets, indicating it did not influence the effect of thapsigargin. According to these data, PP1D-1 exerts antiplatelet effects mainly by inhibiting phosphoinositide turnover.

Adenosine Triphosphate↗

PubMed1998

Antiplatelet agents isolated from medicinal plants.

Platelet-vessel wall interaction is an important process in physiological hemostasis and pathological thrombosis. In oriental countries, some medicinal plants have been claimed for uses to improve circulation, induce fibrinolysis or prevent thrombosis. In cooperation with chemists using bioassay-based step-by-step purification, some antiplatelet agents were isolated from plant sources. According to their effects on platelet aggregation, release reaction and signal transductions involved, these antiplatelet agents can be classified into eight groups: 1. platelet-activating factor (PAF) antagonists, 2. collagen-receptor antagonists, 3. thromboxane-receptor antagonists, 4. ADP-receptor agonists, 5. inhibitors of phosphoinositide breakdown, 6. inhibitors of thromboxane formation, 7. agents increasing cyclic nucleotides, and 8. protein kinase C activators. These new pharmacological agents derived from medicinal plant sources may be useful as leads to develop as effective cardiovascular drugs.

Animals↗

PubMed1997

Inhibition of platelet adhesion to collagen by cGMP-elevating agents.

In the present study, we examined the effects and action mechanisms of cGMP-elevating agents on platelet adhesion to collagen fiber. YC-1, a nitric oxide (NO)-independent activator of soluble guanylate cyclase, inhibited both initial and long-term platelet adhesion to collagen, and the inhibitory effect was potentiated by dipyridamole, a selective inhibitor of cGMP-specific phosphodiesterase. Sodium nitroprusside (SNP), a NO-donor, and 8-bromo-cGMP also inhibited the initial platelet adhesion, but inhibited long-term adhesion only in the presence of dipyridamole. Collagen-induced intracellular Ca2+ mobilization and actin polymerization were prevented by YC-1, SNP and 8-bromo-cGMP. Since blockade of Ca2+ mobilization and actin polymerization caused by collagen led to decrease of platelet adhesion, we suggest that the inhibitory activity of cGMP-elevating agents on the adhesion of platelets to collagen is resulting from interference of these signaling pathways.

Actins↗

PubMed1997

YC-1, a nitric oxide-independent activator of soluble guanylate cyclase, inhibits platelet-rich thrombosis in mice.

YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole), a nitric oxide (NO)-independent activator of soluble guanylate cyclase, has been shown to inhibit platelet activation and aggregation in vitro through the generation of cGMP. In the present study, we assessed the antithrombotic effect of YC-1 in models of experimental thrombosis in mice. YC-1 (10, 30 micrograms/g, i.p.)-treated mice showed a prolonged tail bleeding time 30 min after injection (from control 91.0 +/- 6.4 s to 208.6 +/- 22.7 s and 291.8 +/- 42.4 s, respectively). In contrast, aspirin at a dose of 30 micrograms/g (i.p.) prolonged the bleeding time to more than 600 s. Platelet-rich thrombus formation was induced by irradiation of the mesenteric venule with filtered light in mice pretreated intravenously with fluorescein sodium. YC-1 (30 micrograms/g, i.p.) markedly prolonged the occlusion time of irradiated venules (from control 146.1 +/- 19.0 s to 275.6 +/- 24.5 s) in heparinized (1 U/g) mice. In the same condition, aspirin (100 micrograms/g) only slightly prolonged the time required for occlusion (193.2 +/- 13.2 s). In a model of fatal pulmonary thromboembolism induced by intravenous injection of ADP (300 micrograms/g), YC-1 was effective in reducing mortality when administered intraperitoneally at doses of 10-30 micrograms/g. The antithrombotic effect of YC-1 was correlated with the inhibition of ADP-induced platelet aggregation ex vivo. In contrast, aspirin (30, 100 micrograms/g) did not inhibit ADP-induced pulmonary thromboembolism in vivo or platelet aggregation ex vivo. YC-1 (3, 10 micrograms/g) also exhibited profibrinolytic activity ex vivo, as revealed by shortening of the euglobulin clot lysis time. Therefore, YC-1 is an effective antithrombotic agent in preventing thrombosis in animal models, and its antiaggregating and additional profibrinolytic effects may be of potential clinical benefit in the treatment of thromboembolic diseases.

Adenosine Diphosphate↗

PubMed1997

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs.

We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methyl-formamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5-5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 micrograms/kg, i.v.) or substance P (6.5 micrograms/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5-5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 micrograms/kg, i.v.)- or substance P (6.5 micrograms/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs, CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge.

Airway Resistance↗

PubMed1997

Synthesis and antiplatelet, antiinflammatory, and antiallergic activities of 2-substituted 3-chloro-1,4-naphthoquinone derivatives.

A series of 2-substituted 3-chloro-1,4-naphthoquinones was synthesized, and the antiplatelet, antiinflammatory, and antiallergic activities of these compounds were evaluated. The structure-activity relationships in this series were also examined. Most of the 2-alkyl/arylcarboxamido derivatives of 3-chloro-1,4-naphthoquinone showed potent activities with similar trends in each of the activities evaluated.

Animals↗

PubMed1997

A new flavone C-glycoside and antiplatelet and vasorelaxing flavones from Gentiana arisanensis.

A new flavone C-glycoside, isovitexin 6"-O-glucoside (1), and three known flavonoids, quercetin, isovitexin, and luteolin-7-O-beta-D-glucoside, have been further isolated from the whole plant of Gentiana arisanensis Hayata. The new compound was characterized by spectral methods and chemical reactions. The antiplatelet effects of isovitexin 6"-O-glucoside (1), isoorientin (2), 2 peracetate (3), isovitexin (4), luteolin 7-O-beta-D-glucoside (5), luteolin (6), isoorientin 6"-O-glucoside (7), and 7 peracetate (8) were studied using washed rabbit platelets. Of the compounds tested, 6 showed potent antiplatelet effects on arachidonic acid (AA)-induced platelet aggregation (IC50 = 43.5 microM). The effect of 2, 5, and 6 on the contraction of rat thoracic aorta was also studied. Compound 6 depressed markedly the contraction induced by Ca2+ (1.9 mM) in high-K+ (80 mM) medium, with an IC50 of about 156 microM and also inhibited noradrenaline (3 microM)-induced phasic and tonic contractions, with an IC50 of about 68 and 72 microM, respectively.

Animals↗

PubMed1997

Bioactive alkaloids from Illigera luzonensis.

Using antiplatelet aggregation as a guide to fractionation, seven aporphines, actinodaphnine (1), N-methylactinodaphnine (2), launobine (3), dicentrine (4), O-methylbulbocapnine (5), hernovine (7), and bulbocapnine (9), and two oxoaporphines, dicentrinone (6) and liriodenine (8), were isolated from the stems of Illigera luzonensis. Among them, compounds 2, 4, 5, 8, and 9 were isolated for the first time from this species. Moreover, compounds 1-5, and 8 showed significant antiplatelet aggregation and compounds 1 and 6 exhibited significant vasorelaxant activities, respectively.

Alkaloids↗

PubMed1997

Cytotoxic and antiplatelet aggregation principles from Aglaia elliptifolia.

Two related 1H-2,3,3a,8b-tetrahydrocyclopenta[b]benzofurans, aglafolin (1a) and rocaglamide (2), isolated from the stems of Aglaia elliptifolia, showed significant cytotoxicity in six cancer cell lines. Aglafolin (1a) was also found to completely block platelet aggregation caused by arachidonic acid and platelet-activating factor at 100 microM and 2 ng/mL, respectively.

Animals↗

PubMed1997

Bioactive constituents of Morus australis and Broussonetia papyrifera.

The biological activities of the active principles of two plants in the Moraceae have been investigated. A new prenylflavonoid, australone A (1), and a new triterpenoid, 3 beta-[(m-methoxybenzoyl)oxy]urs-12-en-28-ioc acid (2) were isolated from the root bark of Morus australis, and their structures determined by spectroscopic methods. Also isolated from this plant were seven known compounds, morusin (3), kuwanon C (4), betulinic acid, beta-amyrin, quercetin, ursolic acid, and compound A. Morusin (3) showed significant effects on arachidonic acid-, collagen-, and PAF-induced platelet aggregation, while kuwanon C (4) was active in the arachidonic acid- and PAF-induced platelet aggregation assays. In biological work on a second plant, Broussonetia papyrifera, broussoflavonols F (5) and G (6), broussoflavan A (7), and broussoaurone A (8) potently inhibited Fe(2+)-induced lipid oxidation in rat-brain homogenate. Compounds 5-7 also significantly inhibited the proliferation of rat vascular smooth muscle cells.

Animals↗

PubMed1997

Activation by high potassium of a novel voltage-operated Ca2+ channel in rat spleen.

1. High potassium produced a concentration-dependent contraction in rat isolated spleen. 2. The high potassium-induced contraction of rat spleen was abolished in Ca(2+)-free Krebs solution containing 1 mM EGTA, and the subsequent addition of 3 mM Ca2+ restored the high potassium-induced contraction to the control level. 3. Nifedipine, verapamil, diltiazem, Cd2+, Ni2+, Co2+, R-(+)-Bay K 8644 and pimozide inhibited and relaxed high potassium-induced contraction of rat spleen with IC50 and EC50 values much higher than those values in rat aorta. 4. In addition, high potassium-stimulated contraction of rat spleen was insensitive to omega-conotoxin GVIA, omega-conotoxin MVIIC and omega-agatoxin IVA. 5. The high potassium-induced contraction of rat spleen was also unaffected by tetrodotoxin (TTX), prazosin, chloroethylclonidine (CEC), yohimbine, propranolol, atropine, diphenhydramine, cimetidine, ketanserin, 3-tropanyl-indole-3-carboxylate, saralasin, indomethacin, nordihydroguaiaretic acid, GR32191B, domperidone, naloxone, chlorpromazine, suramin, (+/-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione (DNQX), L-659,877, L-703,606, lorglumide, PD 135,158 N-methyl-D-glucamine, benextramine, amiloride, dantrolene, TMB-8, econazole, staurosporine and neomycin. 6. Forskolin and sodium nitroprusside relaxed high potassium-induced contraction of rat spleen with EC50 values of 0.55 +/- 0.04 and 20.0 +/- 2.7 microM, respectively. 7. It is concluded that high potassium may activate a novel, pharmacologically uncharacterized voltage-operated Ca2+ channel in rat spleen.

Animals↗

PubMed1997

Bakkenolide G, a natural PAF-receptor antagonist.

Because platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) participates in many physiopathological responses, including inflammatory reaction, endotoxic shock, allergic diseases and platelet aggregation, PAF-receptor antagonists are important in the treatment of these diseases. A biologically active compound, bakkenolide G, extracted from the plant Petasites formosanus selectively and concentration-dependently inhibited PAF-induced platelet aggregation and ATP release. The IC50 of bakkenolide G for PAF (2 ng mL(-1))-induced platelet aggregation was 5.6 +/- 0.9 microM. Bakkenolide G also concentration-dependently inhibited PAF-induced intracellular signal transductions, including thromboxane B2 formation, and increased intra-cellular calcium concentration and phosphoinositide breakdown without affecting those caused by thrombin (0.1 units mL(-1)), collagen (10 microg mL(-1)), arachidonic acid (100 microM) and U46619 (1 microM). Bakkenolide G shifted the concentration-response curves of PAF-induced platelet aggregation parallel to the right; the Schild plot slope and the pA2 value were 1.31 +/- 0.31 and 6.21 +/- 0.75, respectively. Moreover, bakkenolide G concentration-dependently competed with [3H]PAF binding to platelets, with an IC50 value of 2.5 +/- 0.4 microM. These data strongly indicate that bakkenolide G is a specific PAF-receptor antagonist as an antiplatelet aggregatory agent.

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

PubMed1997

Antiplatelet effects of some aporphine and phenanthrene alkaloids in rabbits and man.

Two aporphines (boldine and laurolitsine) and five phenanthrene alkaloids (litebamine, secoboldine, N-cyanosecoboldine, N-methylsecoglaucine and N-methylsecopredicentrine) were evaluated in-vitro for their ability to inhibit platelet aggregation. All seven alkaloids inhibited aggregation of rabbit platelets and inhibited the release of ATP induced by arachidonic acid and collagen in rabbit platelets. Those aggregations induced by platelet-activating factor (PAF), thrombin, U46619 and ADP were inhibited by the three N-substituted secoboldine derivatives only. Thromboxane B2 formation caused by arachidonic acid was also suppressed by these compounds. They did not affect the generation of [3H]inositol monophosphate caused by collagen, PAF and thrombin in the presence of indomethacin. Platelet cyclic AMP level was unaffected by litebamine, but was increased by N-methylsecoglaucine. Litebamine suppressed the secondary aggregation, but not the primary aggregation, induced by ADP and adrenaline in platelet-rich plasma from man, whereas N-methylsecoglaucine inhibited both primary and secondary aggregation. It is concluded that the antiplatelet effect of these seven aporphine and phenanthrene alkaloids is mainly a result of inhibition of thromboxane A2 formation; N-methylsecoglaucine has additional antiplatelet activity as a result of increasing the levels of platelet cyclic AMP.

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

PubMed1997

2',5'-Dihydroxychalcone as a potent chemical mediator and cyclooxygenase inhibitor.

Eleven chalcone derivatives have been tested for their inhibitory effects on platelet aggregation in rabbit platelet suspension and the activation of mast cells and neutrophils. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the compounds and some also had a potent inhibitory effect on collagen-induced platelet aggregation and cyclooxygenase. Some hydroxychalcone derivatives showed strong inhibitory effects on the release of beta-glucuronidase and lysozyme, and on superoxide formation by rat neutrophils stimulated with the peptide fMet-Leu-Phe (fMLP). We found that the anti-inflammatory effect of 2',5'-dihydroxychalcone was greater than that of trifluoperazine. 2'5'-Dihydroxy and 2',3,4,5'-tetrahydroxyl chalcones, even at low concentration (50 microM), tested in platelet-rich plasma from man almost completely inhibited secondary aggregation induced by adrenaline. These results suggest that the anti-platelet effects of the chalcones are mainly a result of inhibition of thromboxane formation.

Animals↗

PubMed1997

Synthesis and antiplatelet evaluation of alpha-methylene-gamma-butyrolactone bearing 2-methylquinoline and 8-hydroxyquinoline moieties.

In a search for inhibitors of platelet aggregation, some alpha-methylene-gamma-butyrolactones bearing 2-methylquinoline and 8-hydroxyquinoline moieties were synthesized and evaluated for antiplatelet activities against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. With the exception of 2-[[2,3,4,5-tetrahydro-4-methylene-5-oxo-2-(4-phenylphenyl)-2 -furanyl]methoxy]-8-hydroxyquinoline (8f), these alpha-methylene-gamma-butyrolactones completely inhibited the platelet aggregation induced by AA and Col. The 2-methylquinoline derivatives were also active against Thr- and PAF-induced aggregation, while their 8-hydroxyquinoline counterparts were relatively inactive.

4-Butyrolactone↗

PubMed1997

Pharmacological evaluation of ocoteine, isolated from Cassytha filiformis, as an alpha 1-adrenoceptor antagonist in rat thoracic aorta.

Ocoteine, isolated from Cassytha filiformis, was found to be an alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of phenylephrine-induced vasoconstriction (pA2 = 7.67 +/- 0.09). Removal of endothelium from the aorta did not affect its antagonistic potency (pA2 = 7.97 +/- 0.07). [3H]-Inositol monophosphate formation caused by noradrenaline (3 microM) was suppressed by ocoteine (10 microM) and prazosin (3 microM). Ocoteine did not affect the contraction induced by U-46619, prostaglandin F2 alpha or angiotensin II, but inhibited slightly those by high K+ and endothelin I. Neither the cyclic AMP nor cyclic GMP content of rat thoracic aorta was changed by ocoteine (10 microM). Comparing the EC50 values, the potency of ocoteine against 5-hydroxytryptamine (5-HT) was about 60 times less than that against phenylephrine. Ocoteine (10 microM) also slightly antagonized the clonidine-induced inhibition of the twitch response evoked by field stimulation in rat vas deferens. In guinea pig trachea, the contraction caused by carbachol, histamine, neurokinin A or leukotriene C4 and beta 2-adrenoceptor-mediated relaxing responses induced by isoprenaline were not affected by ocoteine (10 microM). The voltage clamp study in rat ventricular single myocytes revealed that ocoteine (3, 10 microM) inhibited steady state outward currents, but not transient outward currents or slow inward Ca2+ currents. It is concluded that ocoteine is a selective alpha 1-adrenoceptor antagonist in isolated rat thoracic aorta. At high concentrations, it also blocks 5-HT receptors and Na+ and steady state outward currents in rat ventricular myocytes.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1997

ADP-mimicking platelet aggregation caused by rugosin E, an ellagitannin isolated from Rosa rugosa Thunb.

Among the nine ellagitannins, rugosin E was the most potent platelet aggregating agent with an EC50 of 1.5 +/- 0.1 microM in rabbit platelets and 3.2 +/- 0.1 microM in human platelets. The aggregations caused by rugosin E and ADP were inhibited by EGTA, PGE1, mepacrine, sodium nitroprusside and neomycin, but not by indomethacin, verapamil, TMB-8, BN52021 and GR32191B. Rugosin E-induced thromboxane formation was suppressed by indomethacin, EGTA, PGE1, verapamil, mepacrine, TMB-8 and neomycin. ADP-scavenging agents, such as CP/CPK and apyrase inhibited concentration-dependently ADP (20 microM)-, but not rugosin E (5 microM)-induced platelet aggregation. In thrombin (0.1 U/ml)-treated and degranulated platelets, rugosin E and ADP still caused 63.5 +/- 3.0% and 61.2 +/- 3.5% of platelet aggregation, respectively. Selective ADP receptor antagonists, ATP and FSBA inhibited rugosin E- and ADP-induced platelet aggregations in a concentration-dependent manner. Both rugosin E and ADP did not induce platelet aggregation in ADP (1 mM)-desensitized platelets. In contrast to ADP, rugosin E did not decrease cAMP formation in washed rabbit platelets. Both rugosin E and ADP did not cause phosphoinositide breakdown in [3H]myo-inositol-labeled rabbit platelets. In fura-2/AM-load platelets, both rugosin E and ADP induced increase in intracellular calcium concentration and these responses were inhibited by ATP and PGE1. All these data suggest that rugosin E may be an ADP receptor agonist in rabbit platelets.

Adenosine↗

PubMed1996

Antioxidant properties of isotorachrysone isolated from Rhamnus nakaharai.

Isotorachrysone inhibited iron-induced lipid peroxidation with an IC50 value of 1.64 +/- 0.08 microM in rat brain homogenates, and was comparable in potency to butylated hydroxytoluene and was more potent than alpha-tocopherol or desferrioxamine. The mechanism of antioxidant properties were then examined. Isotorachrysone could scavenge the stable free radical diphenyl-p-picrylhydrazyl. And it was an efficient direct scavenger of water-soluble peroxyl radicals with stoichiometry factor of 0.53 +/- 0.05 in the aqueous phase and also toward lipid-soluble peroxyl radicals in tissue homogenates. The oxygen consumption during peroxidation induced by radicals on human erythrocyte ghosts was suppressed by isotorachrysone. Furthermore, it was reactive towards superoxide anion with a second-order rate constant of 5.06 +/- 0.65 x 10(5) M-1 S-1. But it did not react with hydrogen peroxide detected within the sensitivity limit of our assay. Using ascorbate/iron ion/H2O2 as a hydroxyl radical generating system and deoxyribose as a probe, isotorachrysone was effective with hydroxyl radicals with a second-order rate constant of 3.88 +/- 0.54 x 10(11) M-1 S-1 under stimulation by iron-EDTA. On the other hand, isotorachrysone retarded the peroxidation of human low density lipoprotein (LDL) initiated by both aqueous and lipophilic peroxyl radicals. And it also suppressed copper-catalyzed human LDL oxidation, as measured by fluorescence intensity, electrophoretic mobility, and thiobarbituric acid-reactive substances formation in a concentration-dependent manner. Our results show that isotorachrysone is potentially an effective and versatile antioxidant, and can help protecting LDL against oxidation.

Animals↗