Biomedical subjects

C M Teng

Publications and source records attributed to C M Teng.

At least 109 records · Page 6Linked to original sources

PubMed1996

Antiplatelet effect of demethyldiisoeugenol.

A semisynthetic chemical compound, demethyldiisoeugenol, concentration dependently inhibited platelet aggregation and ATP release stimulated by thrombin (0.1 U/mL), platelet-activating factor (2 ng/mL), arachidonic acid (100 microM), collagen (10 micrograms/mL), and U46619 (1 microM) in rabbit washed platelets. The IC50 values of demethyldiisoeugenol on the inhibition of platelet aggregation induced by these five agonists were 157.3 +/- 22.3, 156.2 +/- 12.9, 53.6 +/- 4.7, 54.5 +/- 3.9, and 87.7 +/- 3.2 microM, respectively. Demethyldiisoeugenol also inhibited thromboxane B2 formation induced by thrombin, platelet-activating factor, arachidonic acid, and collagen, and prostaglandin D2 formation was induced by arachidonic acid. The rising intracellular Ca2+ concentration stimulated by these five platelet aggregation inducers was inhibited by demethyldiisoeugenol, while formation of inositol monophosphate was unaffected. Platelet cAMP and cGMP levels were unchanged by demethyldiisoeugenol. It is concluded that demethyldiisoeugenol may directly inhibit both intracellular calcium mobilization and cyclooxygenase activity in platelets.

Adenosine Triphosphate↗

PubMed1996

Pharmacological characteristics of BDTI, a new isoquinoline-derived beta 2-adrenoceptor agonist, in canine trachea and rat heart.

The tracheal relaxing effects and beta 2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other beta-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 +/- 0.08) > BDTI (6.11 +/- 0.06) approximately salbutamol (6.14 +/- 0.08). ICI-118,551 (a selective beta 2-antagonist) and atenolol (a selective beta 1-antagonist) inhibited the relaxant action of BDTI with pKB values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The Kd values of radioligand ([3H]-CGP12177) were 453.3 +/- 30.8 and 563.4 +/- 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the Bmax values were 64.6 +/- 10.7 and 245.7 +/- 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (Ki 0.73 +/- 0.15, 0.75 +/- 0.21 and 0.24 +/- 0.05 mumol/l, respectively) and rat cardiomyocytes (Ki 2.76 +/- 0.36, 2.31 +/- 0.26 and 0.22 +/- 0.03 mumol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to beta 2-adrenoceptors as judged from the Ki (heart)/Ki (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 +/- 0.2 and 0.4 +/- 0.1 mumol/l, respectively) and rat cardiomyocytes (EC50 6.2 +/- 0.5 and 5.7 +/- 0.6 mumol/l, respectively). The selectivity of BDTI and salbutamol for beta 2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a beta 2-selective adrenoceptor agonist.

Adrenergic beta-2 Receptor Agonists↗

PubMed1996

Synthesis and antiplatelet, antiinflammatory and antiallergic activities of 2,3-disubstituted 1,4-naphthoquinones.

Modification of 2-acetamido-3-chloro-1,4-naphthoquinone, which has potent antiplatelet, antiallergic and antiinflammatory activities, led to a series of 2,3-disubstituted 1,4-naphthoquinones. Some of these compounds showed significant antiplatelet, antiallergic and antiinflammatory activities. Among them, 2-methoxy-3-chloro-1,4-naphthoquinone (15) and 2-ethoxy-3-chloro-1,4-naphthoquinone (17) exhibited potent inhibitory effects on neutrophil and mast cell degranulation. 2-Methoxy-1,4-naphthoquinone (20) and 2-ethoxy-1,4-naphthoquinone (21) exhibited potent inhibitory effect on neutrophil superoxide formation. These four compounds were thus selected for further evaluation.

Animals↗

PubMed1996

Synthesis and evaluation of coumarin alpha-methylene-gamma-butyrolactones: a new class of platelet aggregation inhibitors.

In a search for new inhibitors of platelet aggregation, certain coumarin-bearing alpha-methylene-gamma-butyrolactones were synthesized and evaluated for inhibitory activity against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. These compounds were efficiently synthesized from commercially available 7-hydroxycoumarin or its derivatives. Among them, 7-[(2,3,4,5-tetrahydro-4-methylene-5-oxo-2-phenyl-2-furanyl) methoxy]-2H-1-benzopyran-2-one (3d) showed the most potent inhibition of AA- and PAF- induced aggregation, with IC50 values of 3.65 and 16.36 microM respectively.

Adenosine Triphosphate↗

PubMed1995

Inhibition on platelet activation by shikonin derivatives isolated from Arnebia euchroma.

Acetylshikonin, teracrylshikonin, beta,beta-dimethylacrylshikonin and shikonin, isolated from Arnebia euchroma, inhibited collagen (10 micrograms/ml)-induced aggregation of washed rabbit platelets in a concentration-dependent manner with IC50 values of 2.1 +/- 0.2, 2.8 +/- 0.3, 4.2 +/- 0.5 and 10.7 +/- 0.7 microM, respectively. Acetylshikonin also inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA, 100 microM), U46619 (1 microM), platelet-activating factor (PAF, 3.6 nM) and thrombin (0.1 U/ml) in a concentration-dependent manner. The IC50 values of acetylshikonin on the inhibition of these four agonists-induced platelet aggregation were 3.1 +/- 0.4, 2.2 +/- 0.2, 8.0 +/- 0.6 and 12.7 +/- 1.0 microM, respectively. The thromboxane B2 formation caused by collagen, PAF and thrombin was inhibited by acetylshikonin, while formations of thromboxane B2 and prostaglandin D2 caused by AA were not inhibited. Acetylshikonin did not inhibit cyclooxygenase activity since it did not attenuate prostaglandin E2 formation after incubation of sheep vesicular gland microsomes with AA. Acetylshikonin suppressed both the rise of intracellular Ca2+ concentration and the generation of [3H]inositol monophosphate caused by these five aggregation inducers. Platelet cyclic AMP level was unaffected by acetylshikonin. These data indicate that acetylshikonin inhibits platelet activation by suppression of phosphoinositide breakdown.

Animals↗

PubMed1995

Pharmacological evaluation of N-methyl-actinodaphnine, a new vascular alpha-adrenoceptor antagonist, isolated from Illigera luzonensis.

The pharmacological activity of N-methyl-actinodaphnine, isolated from Illigera luzonensis, was determined by functional and binding experiments with peripheral tissues. In a functional study, N-methyl-actinodaphnine was a simple competitive antagonist of contractions elicited by phenylephrine (pA2 = 7.11) in rat thoracic aorta; it also competitively antagonised the clonidine-induced inhibition of the twitch response of rat vas deferens (pA2 = 5.01). In addition, [3H]inositol monophosphate formation caused by noradrenaline (3 microM) in rat isolated thoracic aorta was concentration dependently inhibited by N-methyl-actinodaphnine (1 and 10 microM); however, it had no effect on cyclic AMP and cyclic GMP contents. Additionally, N-methyl-actinodaphnine had extremely low affinity for thromboxane receptors, prostaglandin receptors, Ca2+ channels, muscarinic receptors, histamine receptors, beta-adrenoceptors, neurokinin and leukotriene receptors in vitro. However, N-methyl-actinodaphnine also possessed 5-hydroxytryptamine (5-HT) receptor blocking activity. Its potency for blocking 5-HT receptors was about 14 times less than that for blocking alpha 1-adrenoceptors. In binding experiments, N-methyl-actinodaphnine displaced biphasically the binding of 0.2 nM [3H]prazosin to cultured A10 cells. The selectivity for alpha 1-adrenoceptor subtypes was also investigated in rat vas deferens and spleens. The contractile response in rat vas deferens to noradrenaline was competitively inhibited by N-methyl-actinodaphnine with a pA2 value of 6.58; N-methyl-actinodaphnine also competitively antagonized the phenylephrine-induced contraction in rat spleen with a pA2 value of 7.38. These results indicate that N-methyl-actinodaphnine is a selective alpha 1-adrenoceptor antagonist. Furthermore, it is more selective for the alpha 1B- than for the alpha 1A-adrenoceptor subtype.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1995

Daphnoretin-induced respiratory burst in rat neutrophils is, probably, mainly through protein kinase C activation.

Daphnoretin, a dicoumarin isolated from Wikstroemia indica C.A. Mey. (Thymelaceae), induced superoxide anion (O2-) formation in rat neutrophils in a concentration-dependent manner. Addition of staurosporine reduced daphnoretin-induced respiratory burst. Removal of extracellular free Ca2+ by EGTA did not affect the respiratory burst of neutrophils in response to daphnoretin. Prior exposure of neutrophils to phorbol 12-myristate 13-acetate (PMA) or daphnoretin reduced the O2- formation caused by a subsequent challenge with PMA and daphnoretin, but potentiated the response caused by a subsequent addition of formyl-Met-Leu-Phe (fMLP). Like PMA, daphnoretin did not increase the [Ca2+]i during cell activation. In neutrophil suspension, daphnoretin increased the membrane associated protein kinase C activity. In the presence of Ca2+ and phosphatidyl-serine, daphnoretin also activated protein kinase C isolated from cytosolic fraction of resting neutrophils. Staurosporine inhibited the direct activation of protein kinase C caused by daphnoretin as well as by PMA. Daphnoretin reduced the [3H]Phorbol-12,13-dibutyrate ([3H]PDB) binding to the neutrophil cytosolic protein kinase C in a concentration-dependent manner with an IC50 value of 1.77 +/- 0.37 microM. These results indicate that daphnoretin, like PMA, may direct activation of protein kinase C which in turn activated NADPH oxidase and elicited respiratory burst.

Animals↗

PubMed1995

Effects of CIS-19, a novel PAF receptor antagonist, on PAF-induced eosinophil recruitment and enhancement of superoxide anion generation in guinea-pigs.

We examined the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3,4-dimethoxyphenyl)-6-isopropoxy-7-methoxyl-1-(N-methylforma mido)- 1,2,3,4-tetrahydronaphthalene], on PAF-induced inflammatory cells recruitment into airways and enhancement of superoxide anion (O2-) generation from cells retrieved by bronchoalveolar lavage (BAL) in urethane-anesthetized guinea-pigs. Administration of PAF (30 ng/kg, i.v.) produced a selective increase of eosinophils into airways, but no significant increase of the number of macrophages, neutrophils or lymphocytes. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited the eosinophil recruitment induced by PAF. In vitro, PAF, phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) directly stimulated generation of O2- from BAL cells in a concentration-dependent manner. CIS-19 (10(-7)-10(-4) M) inhibited production of O2- induced by PAF (10(-7) M) in a concentration-dependent manner with an EC50 value of 0.84 microM, but not induced by PMA (0.5 microgram/ml) or FMLP (10(-7) M). Administration of PAF (5 ng/kg, i.v.) enhanced markedly PMA (0.5 microgram/ml) and FMLP (10(-7) M)-induced generation of O2- by 80.2% and 51.3%, respectively. The enhancing effect of PAF was maximal in cells harvested 5 min after the addition of PAF and then declined to baseline level at 60 min. These responses were inhibited by administration of CIS-19 (0.5-2.5 mg/kg, i.v.) or BN 52021 (5 mg/kg, i.v.). The results indicate that CIS-19 is potent in inhibition of PAF-induced airway inflammatory response and may have therapeutic potential as an anti-inflammatory drugs.

Animals↗

PubMed1995

Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium.

Six new coumarins, schinicoumarin, acetoxyaurapten, epoxycollinin, schininallylol, schinilenol and schinindiol, along with seven known coumarins, aurapten, collinin, epoxyaurapten, hydrangetin, umbelliferone, acetoxycollinin and aesculetin dimethyl ether, three known alkaloids, norchelerythrine, dictamnine and skimmianine, and two triterpenoids, beta-amyrin and friedelin, were isolated and characterized from the chloroform-soluble part of the bark of Zanthoxylum schinifolium. The structures of these compounds were elucidated by spectral analyses. Separation accompanied by bioassay-guided fractionation resulted in the isolation of seven compounds with strong inhibitory activity on platelet aggregation in vitro. These are schinicoumarin, acetoxyaurapten, schininallylol, aurapten, collinin, (-)-acetoxycollinin and dictamnine.

Animals↗

PubMed1995

Novel antiplatelet naphthalene from Rhamnus nakaharai.

A new naphthalene derivative, isotorachrysone [1], was isolated from the stem bark of Rhamnus nakaharai along with several known compounds. The antiplatelet effects of isotorachrysone [1], isotorachrysone peracetate [2], 6-methoxysorigenin [3], quercetin 3-O-methyl ether [4], and quercetin 3-O-methyl ether peracetate [5] were studied using washed rabbit platelets. Of the compounds tested, 1, 2, 4, and 5 showed potent antiplatelet effects on arachidonic acid (AA-) and collagen-induced platelet aggregation. Compound 5 also showed potent antiplatelet effects on platelet-activating factor-(PAF-) induced platelet aggregation. Isotorachrysone [1] and its peracetate [2] were also studied for antiplatelet activity in human platelet-rich plasma (PRP) and both showed potent inhibition of the secondary aggregation induced by epinephrine. The antiplatelet effects of 1 and 2 are due partially to an inhibitory effect on thromboxane formation.

Animals↗

PubMed1995

Bioactive constitutents from the stems of Annona montana.

Three structurally related acid amides, N-trans-feruloyltyramine (1), N-p-coumaroyltyramine (2), and N-trans-caffeoyltyramine (3), one lignan, (-)-syringaresinol (4), one aromatic aldehyde, syringaldehyde (5), and two steroids, beta-sitosterol and beta-sitosterol-beta-D-glucoside were isolated from the stem parts of Annona montana (Annonaceae). N-trans-Caffeoyltyramine (3) is a new natural compound. These compounds and their acetate derivatives were subjected to the antiplatelet aggregation and cytotoxicity bioassay where some of them showed significant activities.

Animals↗

PubMed1995

Potent antiplatelet, anti-inflammatory and antiallergic isoflavanquinones from the roots of Abrus precatorius.

Five isoflavanquinones have been isolated from the roots of Abrus precatorius L. (Leguminosae). Three of them are new and designated as abruquinones D, E, and F. The pharmacological activities of the isoflavanquinones have been evaluated. The results indicated that abruquinones A, B, and D exhibited remarkable inhibitory effects on the platelet aggregation. The IC50 of abruquinones A and B for the inhibition of the platelet aggregation induced by arachidonic acid (AA) and collagen were less than 5 micrograms/ml, and of abruquinone D, was less than 10 micrograms/ml for that induced by AA. On the other hand, abruquinones A, B, D, and F showed strong anti-inflammatory and antiallergic effects. The IC50 of abruquinones A, B, D, and F for the inhibition of superoxide formation were less than 0.3 micrograms/ml, for the inhibition of the release of both beta-glucuronidase and lysozyme from rat neutrophils and the release of both beta-glucuronidase and histamine from mast cells were less than 1 microgram/ml.

Animals↗

PubMed1995

New p-quinonoid aporphine alkaloids and antiplatelet aggregation constituents of Hernandia sonora.

Three minor new p-quinonoid aporphine alkaloids, sonodione (1), demethylsonodione (2), and norsonodione (3), have been additionally isolated from the stem bark of Hernandia sonora. The structures of these compounds were elucidated by spectral analysis. Among the isolates obtained till now, five compounds, ovigerine (4), hernangerine (5), N-methylhernangerine (6), (+)-malekulatine (7), and isovanillin (8) showed moderate antiplatelet aggregation activity in vitro.

Animals↗

PubMed1995

Characterization of alpha 1-adrenoceptor subtypes in tension response of human prostate to electrical field stimulation.

1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical field stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked these effects by only 50%. 3. The contractile responses of rat vas deferens and spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha 1A-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical field stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 microM), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5. The involvement of prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined. Clonidine (3 x 10-9 to 3 x 10- M) blocked concentration-dependently the contractile response to electrical field stimulation of human prostate and this inhibitory effect was reversed by yohimbine (10-7 M). Additionally, the inhibitory effect of CEC (3 x 10-6 to 3 x 10-4 M)to the nerve-mediated contraction was also partially reversed by yohimbine (10-7 M).6. It is suggested that the putative czA-adrenoceptors in human prostate may be functionally confined to the synaptic region whereas only minor populations of the putative alpha 1B- and/or alpha 1c-adrenoceptors exist in this region.

Adrenergic Antagonists↗

PubMed1995

YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase.

1. Our previous study demonstrated that YC-1, a derivative of benzylindazole, is a novel activator of soluble guanylate cyclase (sGC) in rabbit platelets. This work investigated whether the antiplatelet effect of YC-1 was mediated by a nitric oxide (NO)/sGC/cyclic GMP pathway in human platelets. 2. In human washed platelets, YC-1 inhibited platelet aggregation and ATP released induced by U46619 (2 microM), collagen (10 micro ml(-1)) and thrombin (0.1 u ml(-1)) in a concentration-dependent manner with IC50 values of (microM) 2.1 +/- 0.03, 11.7 +/- 2.1 and 59.3 +/- 7.1, respectively. 3. In a 30,000 g supernatant fraction from human platelet homogenate, YC-1 (5-100 microM) increased sGC activity in a concentration-dependent manner. At the same concentration-range, YC-1 elevated cyclic GMP levels markedly, but only slightly elevated cyclic AMP levels in the intact platelets. 4. MY-5445, a selective inhibitor of cyclic GMP phosphodiesterase, potentiated the increases in cyclic GMP caused by YC-1, and shifted the concentration-anti-aggregation curve of YC-1 to the left. In contrast, HL-725, a selective inhibitor of cyclic AMP phosphodiesterase, did not affect either the increases in cyclic nucleotides or the anti-aggregatory effect caused by YC-1. 5. Methylene blue, an inhibitor of sGC, blocked the increases of cyclic GMP caused by YC-1, and attenuated markedly the anti-aggregatory effect of YC-1. The adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA) did not affect YC-1-induced inhibition of platelet aggregation. 6. Haemoglobin, which binds NO, prevented the activation of sGC and anti-aggregatory effect caused by sodium nitroprusside, but did not affect YC-1 response. 7. These results would suggest that YC-1 activates sGC of human platelets by a NO-dependent mechanism, and exerts its antiplatelet effects through the sGC/cyclic GMP pathway.

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

PubMed1995

Characterization of the thromboxane (TP-) receptor subtype involved in proliferation in cultured vascular smooth muscle cells of rat.

1. The effects of the thromboxane A2 (TxA2)-mimetic, U-46619, on the proliferation of vascular smooth muscle cells (VSMCs) were examined in a clonal smooth muscle cell line, A10, which was derived from foetal rat aorta. 2. [3H]-U-46619 bound to A10 cells of passages 18-20 (p18-20) with two classes of sites. The high affinity site showed a Bmax of 3.0 +/- 1.8 fmol mg-1 protein with a KD value 1.0 +/- 0.1 nM, while the low affinity site showed a Bmax of 43.0 +/- 6.0 fmol mg-1 protein and KD value of 129.0 +/- 7.9 nM. However, [3H]-U-46619 bound to A10 cells from passages 28-30 (p28-30) at a single class of site with a Bmax 111.0 +/- 9.0 fmol mg-1 protein and a KD value of 175.4 +/- 22.0 nM. 3. Cinnamophilin and SQ29548 inhibited specific [3H]-U-46619 binding to p18-20 A10 cells in a concentration-dependent manner with Ki values of 390.0 +/- 3.2 and 4.6 +/- 1.0 nM, respectively at a high affinity site, and 2.6 +/- 0.2 microM and 310.0 +/- 6.4 nM, respectively at the low affinity site. 4. U-46619 produced isometric contractions of rat aorta in a concentration-dependent manner with an EC50 7.0 +/- 1.2 nM. Cinnamophilin and SQ29548 antagonized U-46619-induced aortic contractions with pA2 values 6.3 +/- 0.1 and 8.2 +/- 0.2, respectively. 5. U-46619 increased [3H]-thymidine incorporation into DNA of p18-20 and p28-30 A10 cells in aconcentration-dependent manner with EC50 values 362.7 +/- 27.0 and 302.5 +/- 20.1 nm, respectively. The U-46619-induced increase of [3H]-thymidine incorporation into DNA of p28 -30 AO0 cells was potentiatedby PDGF (1 ng ml-1) and FCS (1%) and was inhibited by cinnamophilin (10 microM) and SQ29548 (1 microM)with estimated pKB values 5.4 +/- 1.2 and 6.3 +/- 0.9, respectively.6. Cell cycle analysis revealed that U-46619-increased cell cycle progression was primarily due to a rapidtransition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, U-46619 also increasedprotein synthesis and cell numbers in VSMC. All these effects of U-46619 were inhibited bycinnamophilin and SQ29548.7. U-46619 caused phosphoinositide breakdown and increased the intracellular Ca2+ concentration inVSMC, effects which were blocked by cinnamophilin and SQ29548.8 These data indicate there are two U-46619 binding sites in AlO VSMC. The high affinity site is correlated to U-46619-induced vasoconstriction while the low affinity site is correlated to U-46619-mediated VSMC proliferation. These data also reveal that U-46619 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. Since cinnamophilin inhibits TPreceptor-mediated VSMC proliferation, it may thus hold promising potential for the prevention of atherosclerosis or vascular diseases.

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

PubMed1995

Antiplatelet effect of gingerol isolated from Zingiber officinale.

The purpose of this investigation was to determine the antiplatelet mechanism of gingerol. Gingerol concentration-dependently (0.5-20 microM) inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 (9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha) and thrombin. Gingerol also concentration-dependently (0.5-10 microM) inhibited thromboxane B2 and prostaglandin D2 formation caused by arachidonic acid, and completely abolished phosphoinositide breakdown induced by arachidonic acid but had no effect on that of collagen, PAF or thrombin even at concentrations as high as 300 microM. In human platelet-rich plasma, gingerol and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate (ADP, 5 microM) and adrenaline (5 microM) but had no influence on the primary aggregation. The maximal antiplatelet effect was obtained when platelets were incubated with gingerol for 30 min and this inhibition was reversible. It is concluded that the antiplatelet action of gingerol is mainly due to the inhibition of thromboxane formation.

Adenosine Triphosphate↗

PubMed1995

Synthesis and antiplatelet effects of omega-aminoalkoxylxanthones.

A series of omega-aminoalkoxylxanthones were synthesized and tested in-vitro for their ability to inhibit aggregation of rabbit washed platelets and human platelet-rich plasma (PRP) induced by various inducers. Nine of these compounds showed more potent antiplatelet effects than natural norathyriol tetraacetate on collagen-induced aggregation. The various omega-aminoalkoxyl side chains of the synthesized compounds modified the antiplatelet effects. All the compounds tested in human PRP showed significant inhibition of secondary aggregation induced by adrenaline, suggesting that the antiplatelet effects of these compounds is mainly due to an inhibitory effect on thromboxane formation. These compounds at high concentration also cause vasorelaxing action in rat thoracic aorta.

Animals↗