Five New Bioactive Sesquiterpenes from the Fungus Radulomyces confluens (Fr.) Christ

1998 ◽  
Vol 53 (11-12) ◽  
pp. 939-945 ◽  
Author(s):  
Kerstin Fabian ◽  
Kirsten Lorenzen ◽  
Timm Anke ◽  
Martin Johansson ◽  
Olov Sterner
Keyword(s):  
Platelet Aggregation ◽  
Cytotoxic Activity ◽  
Potent Inhibitor ◽  
Antimicrobial Activities ◽  
Human Platelets ◽  
The Other ◽  
Spectroscopic Techniques ◽  
New Compounds

Abstract The three protoilludanes radulone A (1), radulone B (2) and radudiol (3), the illudalane radulactone (4) and the illudane radulol (5) were isolated from the extracts of the culture fluids of the basidiomycete Radulomyces confluens. The structures of the five new compounds were determined by spectroscopic techniques. Radulone A (1) is a potent inhibitor of human and bovine platelet aggregation stimulated by different agonists, inhibiting preferentially the aggregation of human platelets induced by ADP with an IC50 value of 2 μᴍ . In addition 1 exhibits cytotoxic and antimicrobial activities. The other four compounds exhibited weak antimicrobial and cytotoxic activity.

Interactions Between Blood Platelets and Vascular Endothelium in vitro Studies

1979 ◽  
Author(s):  
M.A. Gimbrone ◽  
K.D. Curwen ◽  
R. I. Handin
Keyword(s):  
Platelet Aggregation ◽  
Vascular Endothelium ◽  
Potent Inhibitor ◽  
Platelet Reactivity ◽  
Blood Platelets ◽  
Primary Cultures ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Platelet Adherence

Endothelial cells (EC) can actively influence the hemostatic response at sites of vascular injury through multiple mechanisms. For example, EC can degrade adenosine diphosphate, release plasminogen activator, and synthesize prostacyclin (PGI2), a potent inhibitor of platelet aggregation. We have examined whether PGI2 also might account for the normal lack of platelet adherence to the uninjured EC surface. In a monolayer adherence assay, radiolabeled human platelets in citrated plasma showed minimal interaction with primary cultures of human EC (<1 platelet adhering per cell). Platelets from aspirin-treated and untreated donors behaved similarly. However, aspirin pretreatment of EC consistently resulted in ~2-fold increases in platelet adherence which could be completely abolished by exogenous PGI2 (0.5–1.0 μg/ml). SV40-transformed human EC (SVHEC), which are deficient in PGI2 production compared to primary EC, showed 10-30 times more platelet adherence. Exogenous PGI2 produced a dose - related (.001-1.0 μg/ml) decrease in platelet adherence to SVHEC but did not result in the basal levels observed with normal EC monolayers. These data suggest that : 1) In addition to its effects on platelet aggregation, PGI2 can influence platelet endothelial cell interactions; 2) The increased platelet reactivity of transformed EC is associated with, but not completely attributable, to decreased PGI2 production; and 3) Factors other than PGI2 may play a role in the thromboresistance of normal vascular endothelium.

Mariannaeapyrone -a New Inhibitor of Thromboxane A2 Induced Platelet Aggregation

2001 ◽  
Vol 56 (1-2) ◽  
pp. 106-110 ◽  
Author(s):  
Kerstin Fabian ◽  
Timm Anke ◽  
Olov Sterner
Keyword(s):  
Platelet Aggregation ◽  
Chemical Structure ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Selective Inhibitor ◽  
Spectroscopic Techniques ◽  
Fungal Metabolite ◽  
Antimicrobial Effects ◽  
The Common ◽  
Induced Aggregation

Abstract Mariannaeapyrone ((E)-2-(1,3,5,7-tetramethyl-5-nonenyl)-3,5-dimethyl-6-hydroxy-4H-pyran-4-one) is a new fungal metabolite isolated from fermentations of the common mycophilic deuteromycete Mariannaea elegans. The chemical structure of the 4-pyrone was determined by spectroscopic techniques. Mariannaeapyrone is a selective inhibitor of the thromboxane A2 induced aggregation of human platelets, whereas only weak cytotoxic and antimicrobial effects could be observed.

Thromboxane-Synthetase Inhibitors Could Be “Large Spectrum” Anti-Aggregating Agents

1981 ◽  
Author(s):  
C Bonne ◽  
B Martin
Keyword(s):  
Platelet Aggregation ◽  
Potent Inhibitor ◽  
Platelet Rich Plasma ◽  
Rat Aorta ◽  
The Other ◽  
Vascular Tissues ◽  
Synthetase Inhibitor ◽  
Compound C ◽  
Thromboxane Synthetase ◽  
Dependent Pathway

“Large spectrum”anti-aggregating activity could be only achieved by agents which increased the c AMP content of platelets. Cyclo-oxygenase inhibitors could only block the Thromboxane (Tx)- dependent pathway of platelet aggregation. Conversely, Tx-synthetase inhibitors could deviate the endoperoxides metabolism to anti-aggregating prostaglandins in particular in the presence of vascular tissues. In this study we have investigated the effect of CBS634 (1-(3-hydroxy- 1 - octenyl)-imidazole nicotinic ester, dichlorhydra- teD, a potent inhibitor of T×A2 synthesis, both on the production of anti-aggregating prosta- glandins and on the simultaneous c AMP synthesis in platelets.Rat aorta fragments pretreated with aspirin were incubated with rat platelet rich plasma in the presence or absence of tested compound, c AMP, T×B2, PGE2 and 6-keto-PGFF1α were determined by radioimmunoassays.In the presence of CBS63U (50μM), T×B2 formation was reduced from 17 ± 2 to 0.2 ng/ml/min. In parallel, PGE production in controls was 1.4 ± 0.6 and 8 ± 1 ng/ml/min in the presence of the drug. On the other hand, 6-keto-PGF1α formation, very low in controls, rose to 4 ±1.2 ng/mV min in the presence of CBS63U. Radiochemical assays performed with c14C)-arachidonate confirmed that metabolic deviation. The increased level of c AMP formed in the presence of T×A2-synthetase inhibitor supports the hypothesis that such a drug could present a “large spectrum”antiaggregating activity.

scholarly journals Acetylcholinesterase and Butyrylcholinesterase Inhibitory Compounds from Corydalis Cava (Fumariaceae)

2011 ◽  
Vol 6 (5) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Jakub Chlebek ◽  
Kateřina Macáková ◽  
Lucie Cahlíková ◽  
Milan Kurfürst ◽  
Jiří Kuneš ◽  
...  
Keyword(s):  
Human Blood ◽  
Inhibitory Activity ◽  
Potent Inhibitor ◽  
The Other ◽  
Spectroscopic Techniques ◽  
Dependent Manner ◽  
Isoquinoline Alkaloids ◽  
Chemical Structures ◽  
Inhibitory Compounds ◽  
Dose Dependent

Tubers of Corydalis cava were extracted with ethanol and fractionated using n-hexane, chloroform and ethanol. Repeated column chromatography, preparative TLC and crystallization led to the isolation of fifteen isoquinoline alkaloids. The chemical structures of the isolated compounds were determined on the basis of spectroscopic techniques and by comparison with literature data. All isolated compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. (+)-Canadaline inhibited acetylcholinesterase as well as butyrylcholinesterase in a dose-dependent manner with IC50 values of 20.1 ± 1.1 μM and 85.2 ± 3.2 μM, respectively. (+)-Canadine, with an IC50 value of 12.4 ± 0.9 μM, was the most potent inhibitor of acetylcholinesterase, whilst (±)-corycavidine and (+)-bulbocapnine were effective inhibitors of butyrylcholinesterase with IC50 values of 46.2 ± 2.4 uM and 67.0 ± 2.1 μM, respectively. The other isolated alkaloids were considered inactive (IC50 > 100 μM).

Secondary metabolites of the aspen fungus Stachybotrys cylindrospora

1993 ◽  
Vol 71 (4) ◽  
pp. 487-493 ◽  
Author(s):  
William A. Ayer ◽  
Shichang Miao
Keyword(s):  
Natural Products ◽  
Antifungal Activity ◽  
Secondary Metabolites ◽  
The Other ◽  
Spectroscopic Techniques ◽  
Blue Stain ◽  
New Compounds

The secondary metabolites produced by the fungus Stachybotrys cylindrospora, which is known to be strongly antagonistic to the blue-stain fungus Ceratocystiopsis crassivaginata, have been examined. The compounds responsible for the antifungal activity are trichodermin (5) and trichodermol (6), two previously known mycotoxins belonging to the trichothecene family. The other metabolites, stachybotrydial (1), stachybotramide (8), and 6,8-dihydroxy-3,5,7-trimethylisochroman (7), although not active against C. crassivaginata, are new natural products. The structures of the new compounds were established by spectroscopic techniques.

Platelet Aggregation Is Stimulated by Lactose-lnhibitable Snake Venom Lectins

1989 ◽  
Vol 62 (02) ◽  
pp. 704-707 ◽  
Author(s):  
Mary L Ogilvie ◽  
JoAnn Wilson Byl ◽  
T Kent Gartner
Keyword(s):  
Platelet Aggregation ◽  
Potent Inhibitor ◽  
Specific Inhibitor ◽  
Human Platelets ◽  
Agkistrodon Contortrix ◽  
Low Levels ◽  
Lachesis Muta ◽  
Agkistrodon Contortrix Contortrix ◽  
Bothrops Atrox ◽  
Induced Aggregation

SummaryFive lactose-specific lectins from snake venoms were tested for the ability to stimulate the aggregation of human platelets. Three of the lectins, bushmaster (Lachesis muta), cottonmouth (Aricistrodon piscivorous leukostoma) and rattlesnake (Crotalus atrox) lectins, consistently stimulated secretion and aggregation. Thrombolectin (Bothrops atrox) occasionally caused aggregation. Copperhead (Agkistrodon contortrix contortrix) lectin did not by itself cause platelet aggregation. Lactose, a specific inhibitor of hemagglutination mediated by these lectins was a potent inhibitor of lectin-induced aggregation. Antiserum specific for bushmaster lectin inhibited aggregation by bushmaster lectin. In contrast, the same antiserum and anti-cottonmouth lectin serum enhanced aggregation by low levels of the other lectins.A variety of substances were assayed in the aggregometer for the ability to inhibit aggregation in response to these lectins. Both secretion and aggregation were inhibited by PGI2 and PGEx. Furthermore, lectin-induced aggregation was completely blocked by trifluoperazine and partially blocked by indomethacin. Monoclonal antibodies specific for GP IIb/IIIa (AP2, A2A9, LJP5, LJCP8) but not monoclonals directed against other platelet membrane proteins (API and AP3) inhibited lectin-induced aggregation. The peptide Arg-Gly-Asp-Ser but not Arg-Ala-Asp-Ser was a potent inhibitor of aggregation.

Potentiating Effect of Adenosine on Other Inhibitors of Platelet Aggregation

1972 ◽  
Vol 27 (02) ◽  
pp. 252-262 ◽  
Author(s):  
M. Murakami ◽  
K. Odake ◽  
M. Takase ◽  
K. Yoshino
Keyword(s):  
Platelet Aggregation ◽  
Inhibitory Action ◽  
Prostaglandin E1 ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
The Other ◽  
Other Hand ◽  
Adp Release

SummaryAdenosine was rapidly incorporated into human platelets, and the inhibitory effect of adenosine on platelet aggregation was correlated with the incorporation process. Adenosine potentiated the inhibitory action of other inhibitors, such as dipyridamole, prostaglandin E1 and Y-3642. The inhibition of aggregation was associated with the preservation of platelet adenine nucleotides and the prevention of ADP release. On the other hand, the radioactive adenine nucleotide pattern of platelets was not substantially affected by inhibitors. The relation of inhibition of aggregation with ADP release was discussed.

scholarly journals Amyloid β protein negatively regulates the human platelet activation induced by thrombin receptor-activating protein

2021 ◽  
Author(s):  
Daisuke Mizutani ◽  
Haruhiko Tokuda ◽  
Takashi Onuma ◽  
Kodai Uematsu ◽  
Daiki Nakashima ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Intracerebral Hemorrhage ◽  
Platelet Activation ◽  
Human Platelet ◽  
Amyloid Β ◽  
Human Platelets ◽  
The Other ◽  
Thrombin Receptor ◽  
Amyloid Β Protein ◽  
Β Protein

Abstract Background: Amyloid β protein (Aβ) is the main product derived from amyloid precursor protein (APP) by sequential enzymatic actions. Deposition of Aβ in the brain parenchyma or cerebral vessels is a primary morphological feature of Alzheimer’s disease (AD). In addition, abnormal accumulation of Aβ in the cerebral vessels is known as cerebral amyloid angiopathy (CAA), which is considered a risk factor for intracerebral hemorrhage, particularly in the elderly. CAA reportedly contributes to the development of vascular cognitive decline in addition to AD. On the other hand, human platelets are recognized as the principal components affecting the onset and progression of AD. Although there are several studies showing that Aβ directly modulates human platelet functions, the exact mechanism underlying the Aβ effects on human platelets remains to be elucidated.Methods: The present study investigated the effects of Aβ on human platelet activation using a platelet aggregometer with laser scattering, followed by western blot analysis and ELISA.Results: Aβ at doses up to 7 µM alone failed to affect platelet aggregation or platelet-derived growth factor (PDGF)-AB secretion. On the other hand, Aβ decreased the platelet aggregation induced by thrombin receptor-activating protein (TRAP), but not collagen or ADP. Aβ also suppressed platelet aggregation induced by SCP0237, a selective protease-activated receptor (PAR)-1 agonist, and A3227, a selective PAR-4 agonist. The PDGF-AB secretion and the phosphorylated-heat shock protein (HSP)27 release by TRAP were inhibited by Aβ. In addition, the TRAP-induced phosphorylation of JNK and the phosphorylation of p38 MAP kinase followed by phosphorylation of HSP27 were reduced by Aβ.Conclusion: The results of the present study strongly suggest that Aβ negatively regulates PAR-elicited human platelet activation. These findings may indicate one of the causes of intracerebral hemorrhage due to CAA.

Two Inhibitors of Platelet Aggregation from a Panus Species (Basidiomycetes)

1994 ◽  
Vol 49 (1-2) ◽  
pp. 132-138 ◽  
Author(s):  
Kirsten Lorenzen ◽  
Timm Anke ◽  
Uwe Anders ◽  
Herman Hindermayr ◽  
Fritz Hansske
Keyword(s):  
Platelet Aggregation ◽  
Carbon Atom ◽  
Potent Inhibitor ◽  
Human Platelet ◽  
The Other ◽  
Human Platelet Aggregation

Two inhibitors of platelet aggregation were isolated from fermentations of Panus sp. 9096. One inhibitor proved to be identical to naematolon (2), an antibiotic previously isolated by S. Backens et al. from several Hypholoma species. The other metabolite, panudial (1), is a new nordrimane (cis-annelation of the bicyclus) lacking the carbon atom in position 10 of the drimane skeleton. Panudial is a potent inhibitor of bovine and human platelet aggregation stimulated by different inducers.

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