Biomedical subjects

C M Teng

Publications and source records attributed to C M Teng.

At least 91 records · Page 5Linked to original sources

PubMed1996

Marchantin H as a natural antioxidant and free radical scavenger.

The antioxidant activity of marchantin H was investigated using various experimental models. Marchantin H inhibited nonenzymatic iron-induced lipid peroxidation in rat brain homogenates with an IC50 value of 0.51 +/- 0.03 microM. It was more potent than desferrioxamine or other classical antioxidants. Marchantin H also suppressed NADPH-dependent microsomal lipid peroxidation with an IC50 value of 0.32 +/- 0.01 microM without affecting microsomal electron transport of NADPH-cytochrome P450 reductase. Marchantin H could scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl and peroxyl radical derived from 2,2 '-azobis(2-amidinopropane) dihydrochloride in aqueous phase, but not the peroxyl radical derived from 2,2 '-azobis(2,4-dimethylvaleronitrile) in hexane. The oxygen consumption during peroxyl radical-induced human erythrocyte ghost oxidation was decreased in a concentration-dependent manner by marchantin H. Furthermore, it was reactive toward superoxide anion generated by the xanthine/xanthine oxidase system. On the other hand, marchantin H inhibited copper-catalyzed oxidation of human low-density lipoprotein, as measured by fluorescence intensity, thiobarbituric acid-reactive substance formation, and electrophoretic mobility in a concentration-dependent manner. Our results indicate that marchantin H is a potentially effective and versatile antioxidant and can be used as a chaperone protecting biomacromolecules against peroxidative damage.

Animals↗

PubMed1996

Mechanism of catecholamine-induced proliferation of vascular smooth muscle cells.

BACKGROUND: Catecholamines have been shown to aggravate atherosclerosis in animals and humans, and abnormal proliferation of vascular smooth muscle cells (VSMC) is a key event in the early stage of atherosclerosis. Catecholamines may be involved in such cell growth. Therefore, a series of experiments using cultured VSMC was performed to elucidate their possible mitogenic effect. METHODS AND RESULTS: We examined the mitogenic effect of catecholamines using rat aortic smooth muscle cells (VSMC) by measuring [3H]thymidine incorporation, checking with flow cytometry, and counting the cell number directly. Furthermore, the catecholamine-activated signal transduction pathway was assessed by measurement of the formation of inositol 1, 4, 5-triphosphate, intracellular Ca2+ concentration, mitogen-activated protein kinase (MAPK) activity, and mitogenic gene expression. Norepinephrine (NE) and phenylephrine stimulated [3H]thymidine incorporation and cell growth. Clonidine and isoproterenol showed little of such effects. Prazosin was more effective than either yohimbine or propranolol in suppressing the mitogenic effect of NE, indicating that catecholamine-induced VSMC proliferation is mediated by alpha 1-adrenoceptors. The alpha 1-adrenoceptor activation was coupled to pertussis toxin-insensitive Gq-protein and triggered phosphoinositide hydrolysis with subsequent activation of protein kinase C and MAPK in VSMC. In response to NE, both 42- and 44-kD MAPK were activated and tyrosine was phosphorylated. alpha 1-Adrenoceptor stimulation with NE also caused accumulation of c-fos, c-jun, and c-myc mRNA. Chloroethylclonidine completely blocked the alpha 1-adrenoceptor-mediated mitogenesis. CONCLUSIONS: The effect of catecholamines appears to be mediated via the activation of the chloroethylclonidine-sensitive alpha 1-adrenoceptors that triggers the phosphoinositide hydrolysis and activates the MAPK pathway, leading to DNA synthesis and cell proliferation.

Animals↗

PubMed1996

Inhibition by tamsulosin of tension responses of human hyperplastic prostate to electrical field stimulation.

Tamsulosin (10(-10)-10(-9) M) or prazosin (10(-9)-10(-8) M) concentration dependently blocked the tension responses to electrical field stimulation (0.3 ms duration, 80 V and 20 Hz) in human hyperplastic prostate with lC50 values of (1.93 +/- 0.26) x 10(-10) M and (2.11 +/- 0.21) x 10(-9) M, respectively. The relative potency of tamsulosin with reference to prazosin was 10.96. The pA2 values for tamsulosin and prazosin against phenylephrine-induced contractions were 10.05 +/- 0.16 and 9.25 +/- 0.07, respectively. The relative potency of tamsulosin with reference to prazosin was 6.31. In the presence of prazosin to block alpha 1-adrenoceptor-mediated responses, nifedipine (10(-5) M), but not tamsulosin (10(-9) M), significantly blocked the tension responses in human hyperplastic prostate induced by increasing [Ca2+]o concentrations (10(-4) to 3 x 10(-3) M) in a Ca(2+)-free environment pre-depolarized with 60 mM K+. Additionally, the effects of prazosin and tamsulosin on electrical field stimulation-evoked [3H]noradrenaline release were studied on the S3/S2 ratios. It appeared that both drugs had little effect on this release reaction, with S3/S2 ratios of 0.96 +/- 0.02 and 0.90 +/- 0.02, respectively. These results indicate that tamsulosin is a potent antagonist against endogenous sympathetic stimulation in human hyperplastic prostate.

Adrenergic alpha-Agonists↗

PubMed1996

N-allylsecoboldine as a novel antioxidant against peroxidative damage.

N-Allylsecoboldine was evaluated for antioxidant properties by studying its ability to react with relevant reactive oxygen species, and its protective effect on human erythrocytes under oxidative stress. Using brain homogenates, we found that N-allylsecoboldine dose dependently inhibited lipid peroxidation (IC50 = 4.80 +/- 0.16 microM) and markedly scavenged stable nitrogen-centered radicals. N-Allylsecoboldine was a very efficient scavenger for inhibiting peroxyl radical-mediated destruction of B-phycoerythrin, with a stoichiometry factor of 4.40 +/- 0.59. It also trapped the hydroxyl radicals with a second-order rate constant of 6.92 +/- 0.86 x 10(9) M-1 S-1. Additionally, human erythrocyte oxidative hemolysis induced by aqueous peroxyl radical or hydrogen peroxide was suppressed by N-allylsecoboldine. It not only attenuated the extent of lipid peroxidation but also decreased the formation of the high-molecular weight proteins and degradation of the band 6 protein in radical-treated erythrocytes. It also inhibited the shortening of Russell's viper venom-clotting time mediated by prelytic radical-treated erythrocytes. In the presence of exogenous oxidative stress, hemolysis and lipid peroxidation were significantly enhanced in beta-thalassemic erythrocytes, as compared to the normal control. These elevated detrimental effects could be prevented by N-allylsecoboldine. It is concluded that N-allylsecoboldine may act as an effective antioxidant and protect cells against oxidative damage.

Amidines↗

PubMed1996

Mechanisms-regulated platelet spreading after initial platelet contact with collagen.

In static condition, 6F1, an anti-glycoprotein Ia/IIa monoclonal antibody, almost completely prevented initial platelet adhesion to fibrillar collagen, but markedly lost its action with prolonged incubation. The platelet adhesion and spreading at the later stage were prevented by adding the peptide GRGDS, aspirin, and apyrase, suggesting that after initial recognition of platelet glycoprotein Ia/IIa with collagen the activation of glycoprotein IIb/IIIa and the release of thromboxane A2/ADP would promote platelet spreading, thus strengthening the stability of adhesion. Both initial platelet adhesion and platelet spreading were prevented by cytochalasin B, an inhibitor of actin polymerization. In contrast, BAPTA (an intracellular Ca2+ chelator) only inhibited platelet spreading. Inhibition of protein kinase C or protein tyrosine kinase by staurosporine or genistein, respectively, had only little effect on platelet adhesion. These data suggest that actin polymerization and intracellular Ca2+ mobilization are involved in the regulation of platelet spreading after initial platelet contact with collagen.

Animals↗

PubMed1996

Antiproliferative effect in rat vascular smooth muscle cells by osthole, isolated from Angelica pubescens.

The antiproliferative effect of osthole on rat vascular smooth muscle cells was examined in this study. A number of mitogenic agents, e.g., foetal-calf serum (10%, v/v) and platelet-derived growth factor (20 ng/ml), and pharmacological agents, e.g., serotonin (10 microM), ionomycin (3 nM), phorbol 12,13-dibutyrate (20 nM) and phorbol myristate acetate (200 nM), were used to induce DNA synthesis in rat vascular smooth muscle cells; these effects were concentration dependently inhibited by osthole and the half-maximal inhibition (IC50) occurred at 13.6 +/- 1.8, 11.8 +/- 1.3, 7.9 +/- 0.9, 7.1 +/- 0.2, 7.8 +/- 0.2 and 8.6 +/- 0.4 microM, respectively. Osthole itself increased the cyclic AMP and cyclic GMP formations in a concentration-dependent manner; it synergistically increase cyclic AMP and cyclic GMP levels induced by forskolin and sodium nitroprusside, respectively. After 48 h deprivation of serum, cells were re-stimulated with serum and the cell cycle was observed by flow cytometry; treatment of cells with osthole (100 microM) caused a block of serum-inducible cell cycle progression at a point before the G1-S boundary. The addition of osthole (100 microM) at various times after serum addition to serum-deprived cells showed full inhibition of DNA synthesis even when added 6 h after serum. The cell cycle progression block was gradually lost as the delay from serum to osthole application was increased from 6 to 18 h. The effect of osthole on serum-stimulated [3H]thymidine incorporation into endothelial cells was examined and the IC50 value (158.7 +/- 2.7 microM, n = 6) was obtained; it exhibited greater potency (12-fold) for vascular smooth muscle cells as compared with endothelial cells as an antiproliferative agent. These results suggest that osthole is a selective antiproliferative agent in vascular smooth muscle cells. The antiproliferative effect occurs at the early G1 phase of the cell cycle and is due to the increase in cyclic AMP and cyclic GMP contents.

Animals↗

PubMed1996

Coumarins and antiplatelet aggregation constituents from Formosan Peucedanum japonicum.

Four new khellactone esters, (-)-trans-3'-acetyl-4'-senecioylkhellactone, (+-)-cis-3'-acetyl-4'-tigloylkhellactone, (+-)-cis-4-tigloylkhellactone, (+)-trans-4'-tigloylkhellactone, together with 14 known coumarins, isoimperatorin, psoralen, bergapten, xanthotoxol, cnidilin, (-)-selinidin, (-)-deltoin, (+)-pteryxin, (+)-peucedanocoumarin III, xanthotoxin, imperatorin, (+)-marmesin, (+)-oxypeucedanin hydrate, (+)-peucedanol and three chromones, eugenin, (-)-hamaudol, (+)-visamminol, have been isolated from the root of Formosan Peucedanum japonicum. The structures of the new compounds were elucidated by spectral data. The identities of (+)-trans-3'-tigloyl-4'-acetylkhellactone, formerly reported as a new compound, and (+)-cis-3'-angeloyl-4'-acetyl-khellactone, with the known (+)-peucedanocoumarin III and (+)-pteryxin, respectively, are discussed. Among the isolates, seven compounds, eugenin, (-)-selinidin, (+)-pteryxin, imperatorin, bergapten, cnidilin and (+)-visamminol, show strong antiplatelet aggregation activity in vitro.

Coumarins↗

PubMed1996

Carbazole alkaloids from Clausena excavata and their biological activity.

Five new carbazole alkaloids, clausines B, E, H, I and K, as well as 22 known compounds, were isolated from the stem bark of Clausena excavata. The structures were established from spectral data and chemical transformation. These compounds showed significant inhibition of rabbit platelet aggregation and caused vasocontraction. The crude methanol extract, partitioned layers and chromatographic fractions revealed the presence of promotive and inhibitive constituents, simultaneously. These results might explain the philosophy of use in Chinese medicine, in that the dose and content variation in a prescription produced different, promotive or inhibitive, effects on therapy.

Alkaloids↗

PubMed1996

Antiplatelet of vasorelaxing actions of some benzylisoquinoline and phenanthrene alkaloids.

Members of a series of benzylisoquinoline and phenanthrene alkaloids were tested for their antiplatelet and vasorelaxing actions. Atherosperminine HClO4 (15) and atherosperminium I (16) showed strong inhibition of adenosine 5'-diphosphate-induced platelet aggregation. dl-N-Methylcoclaurine (1), dl-coclaurine (6), 15, 16, xylopine hydroxylamine (18), and atherosperminine N-oxide (19) showed strong inhibition of arachidonic acid-induced platelet aggregation. Compounds 1, 15, 16, dicentrine methine (17), 18, and 19 showed strong inhibition of collagen-induced platelet aggregation. d-(-)-Magnocurarine I (8), 15, and 16 showed strong inhibition of platelet-activating factor-induced platelet aggregation. Compounds 15, 17, and 19 showed vasorelaxing action in rat thoracic aorta.

Alkaloids↗

PubMed1996

Novel antiplatelet constituents from formosan moraceous plants.

Sixteen constituents from Formosan Moraceous plants were tested for their antiplatelet activities in rabbit platelet suspension and human platelet-rich plasma. Cycloartocarpin A, cycloheterophyllin, broussochalcone A, kazinol A, broussoaurone A, and broussoflavonol F showed strong inhibition of arachidonic acid (AA)-induced platelet aggregation. Of the compounds tested, broussochalcone A exhibited the most potent inhibition of platelet aggregation induced by AA (IC50 = 6.8 microM). The antiplatelet effects of cycloheterophyllin, broussochalcone A, kazinol B, broussoaurone A, and broussoflavonol F are partially due to an inhibitory effect on cyclooxygenase.

Animals↗

PubMed1996

Antiplatelet arylnaphthalide lignans from Justicia procumbens.

Fractionation of the EtOH extract of Justicia procumbens, guided by antiplatelet bioassay, led to the isolation of nine known arylnaphthalide lignans, neojusticin A (1), justicidin B (2), justicidin A (3), taiwanin E methyl ether (4), neojusticin B (5), chinensinaphthol methyl ether (6), taiwanin E (8), chinensinaphthol (9), and diphyllin (10), and a new arylnaphthalide lignan that was characterized by spectral means as 4'-demethylchinensinaphthol methyl ether (7). Compounds 1, 2, 4, and 8 significantly inhibited platelet aggregation.

Animals↗

PubMed1996

Antiplatelet and vasorelaxing actions of some aporphinoids.

A series of aporphines and oxoaporphines was tested for antiplatelet and vasorelaxing actions. (+)-N-Methylactinodaphnine, (-)-norannuradhapurine x HBr, xylopine, actinodaphnine, and N-methylnandigerine showed strong inhibition of adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Boldine, (+)-N-methylactinodaphnine, (-)-norannuradhapurine x HBr, xylopine, N-acetyllaurolitsine, N-methyllaurotetanine, actinodaphnine, N-methylnandigerine, O-methylbulbocapnine, and liriodenine showed strong inhibition of arachidonic acid (AA)-induced platelet aggregation. (+)-N-Methylactinodaphnine, fissoldine x HCIO4, (-)-norannuradhapurine x HBr, xlylopine, N-methyllaurotetanine, actinodaphnine, N-methylnandigerine, O-methylbulbocapnine, and liriodenine showed strong inhibiton of collagen-induced platelet aggregation. (-)-Norannuradhapurine x HBr, xylopine, N-methyllaurotetanine, and actinodaphnine showed strong inhibition of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)-induced platelet aggregation. (+)-N-Methylactinodaphnine, laurotetanine, N-methylactinodaphnine N-oxide, oxoglaucine, boldine, and actinodaphnine showed vasorelaxing action in rat thoracic aorta. The results are discussed on the basis of structure-activity relationships.

Adenosine Diphosphate↗

PubMed1996

Indolopyridoquinazoline alkaloids with antiplatelet aggregation activity from Zanthoxylum integrifoliolum.

Bioassay-guided fractionation led to the isolation of three indolopyridoquinazoline alkaloids, 1-hydroxyrutaecarpine, rutaecarpine, and 1-methoxyrutaecarpine as the active principles of antiplatelet aggregation in vitro, from the chloroform-soluble part of the fruit of Zanthoxylum integrifoliolum (Rutaceae). 1-Hydroxyrutaecarpine exhibited antiplatelet activity induced by AA and showed an IC50 value of ca. 1-2 micrograms/ml.

Alkaloids↗

PubMed1996

Ouabain-induced increases in resting tone of human hyperplastic prostate following repeated noradrenaline and electrical field stimulation.

1. The effect of ouabain on contractions to repeated noradrenaline stimulation and electrical field stimulation of human hyperplastic prostate was examined. Ouabain (1 microM) did not induce contractile response per se but progressively increased the resting tone (i.e., the tone between one noradrenaline stimulation, or electrical field stimulation, and the following) of human hyperplastic prostate. 2. The increased tone by ouabain following repeated noradrenaline stimulations or electrical field stimulation was fully relaxed by the removal of external calcium, and recovered following restoration of calcium. 3. The effect of noradrenaline on NA+ uptake was measured. Noradrenaline (10 microM) significantly increased the rate of Na+ accumulation in the presence of ouabain (1 microM); this stimulatory effect was almost completely blocked by prazosin (0.1 microM) and ethylisopropylamiloride (100 microM). In contrast, tetrodotoxin (1 microM) had no effect on noradrenaline-stimulated Na+ transport in human hyperplastic prostate. 4. Intracellular Na+ loading by noradrenaline (10 microM) in the presence of ouabain (1 microM) significantly increased the transmembrane Ca2+ uptake as compared with the absence of ouabain; however, nifedipine (1 microM) was ineffective on Ca2+ uptake under this condition. 5. Transmembrane CA2+ efflux was stimulated by noradrenaline (10 microM) in human hyperplastic prostate; this effect was significantly decreased in the presence of ouabain (1 microM). 6. It is suggested that the increased tone of human hyperplastic prostate following repeated excitation in the presence of ouabain is due to increased Ca2+ entry and reduced efflux of Ca2+ through the Na+/Ca+ exchange system as a consequence of Na+ pump inhibition by ouabain.

Adrenergic alpha-Agonists↗

PubMed1996

Induction of calcium release from sarcoplasmic reticulum of skeletal muscle by xanthone and norathyriol.

1. Effects of xanthone and its derivative, 1,3,6,7-tetrahydroxyxanthone (norathyriol), on Ca2+ release and ryanodine binding were studied in isolated sarcoplasmic reticulum (SR) vesicles from rabbit skeletal muscle. 2. Both xanthone and norathyriol dose-dependently induced Ca2+ release from the actively loaded SR vesicles which was blocked by ruthenium red, a specific Ca2+ release inhibitor, and Mg2+. 3. Xanthone and norathyriol also dose-dependently increased apparent [3H]-ryanodine binding. Norathyriol, but not xanthone, produced a synergistic effect on binding activation when added concurrently with caffeine. 4. In the presence of Mg2+, which inhibits ryanodine binding, both caffeine and norathyriol, but not xanthone, could restore the binding to the level observed in the absence of Mg2+. 5. Xanthone activated the Ca(2+)-ATPase activity of isolated SR vesicles dose-dependently reaching 70% activation at 300 microM. 6. When tested in mouse diaphragm, norathyriol potentiated the muscle contraction followed by twitch depression and contracture in either a Ca(2+) -free bathing solution or one containing 2.5 mM Ca2+. These norathyriol-induced effects on muscle were inhibited by pretreatment with ruthenium red or ryanodine. 7. These data suggest that xanthone and norathyriol can induce Ca2+ release from the SR of skeletal muscle through a direct interaction with the Ca2+ release channel, also known as the ryanodine receptor.

Animals↗

PubMed1996

Mechanism of action of p-chlorobiphenyl on the inhibition of platelet aggregation.

p-Chlorobiphenyl (1-50 microM) concentration-dependently 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 and thrombin. The IC50 values of p-chlorobiphenyl on the arachidonic acid and collagen-induced platelet aggregation were 2.9 +/- 0.5 and 12.8 +/- 2.3 microM, respectively. The formation of both platelet thromboxane B2 and prostaglandin D2 caused by arachidonic acid was inhibited by p-chlorobiphenyl concentration-dependently. In myo-[3H]inositol-labeled and fura-2-loaded platelets. [3H]inositol monophosphate generation and the rise in intracellular Ca2- stimulated by arachidonic acid were inhibited by p-chlorobiphenyl. In human platelet-rich plasma, p-chlorobiphenyl and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate and adrenaline without affecting the primary aggregation. It is concluded that p-chlorobiphenyl may be a cyclo-oxygenase inhibitor and its antiplatelet action is mainly due to the inhibition of thromboxane formation.

Adenosine Triphosphate↗

PubMed1996

(+/-)-Govadine and (+/-)-THP, two tetrahydroprotoberberine alkaloids, as selective alpha 1-adrenoceptor antagonists in vascular smooth muscle cells.

(+/-)-Govadine and (+/-)-THP ((+/-)-2,3,10,11-tetrahydroxytetrahydroprotoberberine HBr) have been shown to inhibit noradrenaline-induced contraction of rat thoracic aortae. The pharmacological activity of the compounds was determined in thoracic aortae and cardiac tissue isolated from the rat and in trachea isolated from the guinea-pig to determine the selectivity of the compounds towards different types of receptor. (+/-)-Govadine and (+/-)-THP were found to be alpha 1-adrenoceptor blocking agents in rat thoracic aorta as revealed by their competitive antagonism of vasoconstriction induced by noradrenaline (pA2 = 6.57 +/- 0.07 and 5.93 +/- 0.06, respectively) or phenylephrine (pA2 = 6.74 +/- 0.08 and 6.06 +/- 0.10, respectively). Removal of endothelium did not affect the antagonistic potencies of (+/-)-govadine (pA2 = 6.83 +/- 0.09) and (+/-)-THP (pA2 = 6.25 +/- 0.06) on phenylephrine-induced vasoconstriction. They were more potent than yohimbine (pA2 = 6.05 +/- 0.05), but less so than phentolamine (pA2 = 7.54 +/- 0.11) and prazosin (pA2 = 9.27 +/- 0.12). (+/-)-Govadine and (+/-)-THP, furthermore, inhibited [3H]inositol monophosphate formation caused by noradrenaline (3 microM) in rat thoracic aorta. (+/-)-Govadine and (+/-)-THP were also alpha 2-adrenoceptor blocking agents with pA2 values 5.50 +/- 0.13 and 5.41 +/- 0.11, respectively. A high concentration of (+/-)-govadine (30 microM) or (+/-)-THP (30 microM) did not, however, affect the contraction induced by the thromboxane receptor agonist U46619, prostaglandin F2 alpha (PGF2 alpha), 5-hydroxytryptamine (5-HT), angiotensin II, endothelin or high K+ in rat aorta denuded of endothelium. Neither the cyclic AMP nor cyclic GMP content of rat thoracic aorta was, furthermore, changed by (+/-)-govadine or (+/-)-THP. Contraction of guinea-pig trachea caused by carbachol, histamine, leukotriene C4 or neurokinin A was not affected by (+/-)-govadine or (+/-)-THP. (+/-)-Govadine or (+/-)-THP also did not block beta 1- or beta 2-adrenoceptor-mediated responses induced by isoprenaline in rat right atria and guinea-pig trachea. It is concluded that (+/-)-govadine and (+/-)-THP are selective alpha 1-adrenoceptor antagonists in vascular smooth muscle.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1996

Synthesis and antithrombotic effect of xanthone derivatives.

A series of xanthone derivatives was 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. 2-Prenyloxyxanthone showed the most potent inhibition of rabbit washed platelet aggregation induced by arachidonic acid (1C50 = 10.2 microM). Of the compounds tested in human PRP, 2-[3 (propylamino)-2-hydroxypropoxy]xanthone (4) hydrochloride salt exhibited the most potent inhibition of platelet aggregation induced by adrenaline (IC50 = 4.4 microM), whereas in evaluation of mouse antithrombotic activity, compound 4 exhibited the most potent protection of mice from thrombotic challenge. Compound 4, 2-[3-(isopropylamino)-2-hydroxypropoxylxanthone hydrochloride salt and 2,5 dihydroxyxanthone suppressed the secondary aggregation induced by adrenaline in human PRP. We conclude that the antiplatelet effects of these compounds are mainly due to an inhibitory effect on thromboxane formation.

Animals↗