Inhibitory effects of 2'-hydroxychalcones on rat lens aldose reductase and rat platelet aggregation

Inhibitory effects of synthetic 2'-hydroxychalcone derivatives on rat lens aldose reductase (RLAR) and on platelet aggregation were investigated for the prevention or the treatment of chronic diabetic complications. 5'-chloro-4,2'-dihydroxychalcone (8) and 5'-chloro-3,2'-dihydroxychalcone (27) exhibited a potent inhibitory effect on rat platelet aggregation induced by ADP (IC50=0.10 and 0.06 mg/ml, respectively) and collagen (IC50=44 and 16 microg/ml, respectively) but showed relatively weak inhibitory activities on RLAR.     

Inhibitory effects of phylligenin and quebrachitol isolated from Mitrephora vulpina on platelet activating factor receptor binding and platelet aggregation

Phylligenine, together with quebrachitol, stigmasterol and two aporphine alkaloids--oxoputerine and liriodenine--were isolated from the twigs of Mitrephora vulpina C.E.C. Fisch. They were evaluated for their ability to inhibit platelet activating factor (PAF) receptor binding to rabbit platelets using 3H-PAF as a ligand and their antiplatelet aggregation effect in human whole blood induced by arachidonic acid (AA), collagen and adenosine diphosphate (ADP). Of all the compounds tested, phylligenin and quebrachitol exhibited potent and concentration-dependent inhibitory effects on PAF receptor binding, with IC(50) values of 13.1 and 42.2 μM, respectively. The IC(50) value of phylligenin was comparable to that of cedrol (10.2 μM), a potent PAF antagonist. Phylligenin also showed strong dose-dependent inhibitory activity on platelet aggregation induced by AA and ADP.     

Inhibitory effect of hydrophilic polymer brushes on surface-induced platelet activation and adhesion

Poly(N,N-dimethylacrylamide) (PDMA) brushes are successfully grown from unplasticized poly(vinyl chloride) (uPVC) by well-controlled surface-initiated atom transfer radical polymerization (SI-ATRP). Molecular weights of the grafted PDMA brushes vary from ≈ 35,000 to 2,170000 Da, while the graft density ranges from 0.08 to 1.13 chains · nm(-2). The polydispersity of the grafted PDMA brushes is controlled within 1.20 to 1.80. Platelet activation (expression of CD62) and adhesion studies reveal that the graft densities of the PDMA brushes play an important role in controlling interfacial properties. PDMA brushes with graft densities between 0.35 and 0.50 chains · nm(-2) induce a significantly reduced platelet activation compared to unmodified uPVC. Moreover, the surface adhesion of platelets on uPVC is significantly reduced by the densely grafted PDMA brushes. PDMA brushes that have high molecular weights lead to a relatively lower platelet activation compared to low-molecular-weight brushes. However, the graft density of the brush is more important than molecular weight in controlling platelet interactions with PVC. PDMA brushes do not produce any significant platelet consumption in platelet rich plasma. Up to a seven-fold decrease in the number of platelets adhered on high graft density brushes is observed compared to the bare PVC surface. Unlike the bare PVC, platelets do not form pseudopodes or change morphology on PDMA brush-coated surfaces.     

New platelet aggregation inhibitors

From a cultured broth of Streptomyces matensis A-6621, we isolated three new platelet aggregation inhibitors designated as PI-080, PI-085 and PI-087. The structures of these compounds were established by spectral and chemical methods.     

Cytotoxic activity and cell cycle analysis of hexahydrocurcumin on SW 480 human colorectal cancer cells

The cytotoxicity of hexahydrocurcumin and its effect on the cell cycle in human colorectal cancer cells SW480 has been studied for the first time. The compound, extracted from Zingiber officinale, was shown to be cytotoxic to colorectal cancer cells. Treatment of SW480 cells with hexahydrocurcumin (100 microM) resulted in a massive accumulation of the cells in the G1/G0 phase of the cell cycle. The cytotoxic effect of hexahydrocurcumin may prove useful in cancer prevention.     

Evaluation of angelicae radix (Touki) by the inhibitory effect on platelet aggregation.

Quality evaluation of Angelicae Radix (Touki) was discussed referring to its inhibitory effect on platelet aggregation. No better correlation was observed in quality determined morphologically from the above-ground part of Touki and that determined by anti-platelet aggregation (APA) effects. Phthalides and adenosine, known to be the major components of Touki, were found not sufficient to evaluate the Touki quality as regards APA active components have been studied and it was concluded that the APA effect of Touki results from the combined action of plural components. The importance of determining quality based on the action of total extract to meet the purpose for which the substance is to be used was suggested.     

Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways

Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades.     

Pyrrolidine derivatives as inhibitors of platelet aggregation induced by platelet activating factor

Newly synthesized pyrrolidine derivatives inhibited rabbit platelet aggregation induced by platelet activating factor.     

Inhibitory effects of catechol derivatives on arachidonic acid-induced aggregation of rabbit platelets

Pyrocatechol and other non-substituted dihydric phenols, which have strong redox power, inhibited arachidonic acid-induced aggregation of rabbit platelets at much lower concentrations than those at which these phenols inhibited stable prostaglandin endoperoxide, U46619-induced aggregation. Among non-substituted dihydric phenols, pyrocatechol was most potent. In order to clarify the physicochemical properties of the phenolic compounds which control the inhibitory potencies of dihydric phenols, we observed the inhibitory effects of 3- and 4-substituents of pyrocatechol on arachidonic acid-induced platelet aggregation. Among seven derivatives tested, the inhibitory effect of 4-C6H5-substituent was strongest and 4-COOH-substituent was weakest. Inhibitory effects of the catechol derivatives were well correlated with the quotients of their hydrophobicities and oxidation-reduction potentials. Inhibitory effects of hydroquinone and resorcinol were also on the same correlation line. These results suggest that the inhibitory effects of catechol derivatives and other dihydric phenols are controlled by two physicochemical properties: oxidation-reduction potential and hydrophobicity.     

Screening of anti-platelet aggregation agents from Panax notoginseng using human platelet extraction and HPLC-DAD-ESI-MS/MS

Root of Panax notoginseng (Sanqi in Chinese) is a highly valued and commonly used Chinese medicine. It has been widely used for treatment of cardio- and cerebro-vascular diseases. In this study, a method involving human platelet extraction and HPLC-DAD-ESI-MS/MS was developed for screening potential anti-platelet aggregation agents in Sanqi. Five compounds which could interact with human platelets were found, and four were identified as adenosine, guanosine, ginsenoside Rh1, and ginsenoside F1, respectively. The effects on rabbit platelet aggregation induced by arachidonic acid, adenosine diphosphate, and thrombin were also investigated in vitro. The results showed that the nucleosides adenosine and guanosine mainly contributed to the anti-platelet aggregation of Sanqi. The data suggest that human platelet extraction combined with HPLC-DAD-ESI-MS/MS is a useful method for screening anti-platelet aggregation agents from Chinese medicines.     

Enantioselective synthesis of imperanene, a platelet aggregation inhibitor

Both enantiomers of imperanene, a platelet aggregation inhibitor, have been synthesized in 82-90% ee. The key step of establishing the chiral center was achieved through stereoselective alkylation with benzyl chloromethyl ether using Enders' RAMP/SAMP chiral auxiliary method. The natural product was determined to be the (S)-enantiomer through comparison of optical rotation data. Reaction: see text.     

Temperature effect on the ease of aggregation

The effect of temperature on the critical aggregate concentration (CAgC) has been investigated for the first time, by measurement of the hydrolytic rate constants of p-nitrophenyl dodecanoate (C12) and hexadecanoate (C16) at different temperatures in the 30:70 V/V (Φ=0.30) and 40:60 V/V (Φ= 0.40) dioxane (DX)-H2O systems. The CAgC values of C12 and C16 increase with the increase of the temperature, i.e., high temperatures disfavor aggregation. Activation energies for the hydrolysis of C12 in the monomeric and aggregated concentration domains have also been discussed.     

Inhibitory effect of silibinin on tumour necrosis factor-alpha and hydrogen peroxide production by human monocytes

Silibinin is a chemically defined flavonoid and the main active component of silymarin, a polyphenolic complex from Silybum marianum, which has anti-inflammatory, hepatoprotective and anticarcinogenic properties. Monocytes obtained from healthy individuals were incubated with silibinin to evaluate cell viability, hydrogen peroxide (H(2)O(2)) release and tumour necrosis factor-alpha (TNF-α) production by these cells. The duration of treatment and different silibinin concentrations had no significant effect on cell viability. Monocytes showed a dose-dependent inhibitory effect on H(2)O(2) release by phorbol myristate acetate-stimulated monocytes in silibinin concentrations ranging from 6.25 to 50 μg mL(-1). Significant inhibition of TNF-α production by lipopolysaccharide-stimulated monocytes was observed at concentrations of 12.5, 50 and 100 μg mL(-1) of silibinin. These results suggest that silibinin exerts antioxidant and anti-inflammatory properties on human monocytes through an inhibitory effect on H(2)O(2) release and on TNF-α production, respectively.