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Vascular effects of wine polyphenols
No full textModerate consumption of red wine has been putatively associated with lowering the risk of developing coronary heart disease. This beneficial effect is mainly attributed to the occurrence of polyphenol compounds such as anthocyanosides (ACs), catechins, proanthocyanidins (PAs), stilbenes and other phenolics in red wine. This review focuses on the vascular effects of red wine polyphenols (RWPs), with emphasis on anthocyanosides and proanthocyanidins. From in vitro studies, the effect of red wine polyphenols on the vascular tone is thought to be due to short- and long-term mechanisms. NO-mediated vasorelaxation represents the short-term response to wine polyphenols, which exert the effect by increasing the influx of extracellular Ca2 +, and the mobilization of intracellular Ca2 + in endothelial cells. Polyphenolic compounds may also have long-term properties, as they increase endothelial NO synthase expression acting on the promoter activity. In addition, they decrease the expression of adhesion molecules and growth factors, involved in migration and proliferation of vascular smooth muscle cells. Moreover, they inhibit platelet aggregation. However, a paucity of data as regards the bioavailability and metabolism of these compounds in human studies is a limiting factor to proving their efficacy in vivo
Chamomile infusions inhibit proteases involved in gastric inflammation
No full textChamomile, prepared with dried flowers from Matricaria recutita L., is one of the most commonly consumed herbal tea. The drug is used for the treatment of gastrointestinal complaints (minor spasms, epigastric distensions, gastritis and gastric inflammation). Several classes of bio-active compounds have been identified in the extracts of chamomile including phenolic acids, coumarins, and flavonoids such as the glycosides of apigenin, quercetin, patuletin, luteolin and several derivatives.
Several studies showed that chamomile infusions possess a protective effect on gastritis and gastric ulcer, but the mechanisms involved in this effect are not completely established. Matrix metalloproteinases (MMPs) and neutrophils elastase (NE) are proteases that degrade extracellular matrix in physiological and pathological conditions. Since MMP-9 and NE are involved in gastric inflammation, the aim of this work was the evaluation of the effects of chamomile infusions of dried capitula (CFI) and sifted (SFI) flowers on MMP-9 and NE, and the identification of the compounds responsible for the observed effect. Each infusion was analyzed by LC-MS/MS in order to verify whether compositional differences affected biological activity.
Analysis of CFI and SFI by LC-MS showed a complex profile. The compounds unequivocally identified by LC-MS/MS were the flavonoids apigenin-7-O-glucoside (api7glu), luteolin-7-O-glucoside (lut7glu), patuletin-7-O-glucoside (pat7glu) and hyperoside (hyp). Api7glu was more abundant in CFI than in SFI whereas the opposite was for lut7glu (5.2 μg/ml vs 8.1 μg/ml). Pat7glu was the most abundant in both the infusions, whereas Hyp was the lowest.
CFI and SFI inhibited enzymatic activity of MMP-9 catalytic domain in a concentration-dependent manner. At 1500 microg/ml the inhibition was 28 % and 55 % for CFI and SFI, respectively. Api7glu and lut7glu (10 μM) showed an inhibitory activity of 40% and 30%, respectively, demonstrating their contribute to the effect of the infusions. The inhibitory effect of CFI and SFI was confirmed on MMP-9 released by human adenocarcinoma cells (AGS cells). CFI was able to inhibit MMP-9 secretion from AGS cells (85% at 1500 microg/ml). The inhibitory effect of the infusions on NE was also tested. Concentration-response curves were performed and IC50 of CFI and SFI on NE were 369.2 microg/ml and 536.7 microg/ml, respectively. The individual compounds that showed an inhibitory effect on NE activity were api7glu (IC50 74.3 microM), lut7glu (IC50 8.6 microM), pat7glu (IC50 10.4 microM), and chlorogenic acid (IC50 31.3 microM).
In conclusion, the present study shows some biochemical mechanism of action for the effect of chamomile infusions and supports the use of chamomile in the treatment of gastrointestinal inflammation
Inhibition of NF-kB and metalloproteinase-9 expression and secretion by parthenolide derivatives
No full textSemisynthetic derivatives of parthenolide (1) were tested on NF-kB driven transcription and metalloproteinase-
9 (MMP-9) expression and secretion. The four membered ring compounds 5 and 6, obtained by
acidic treatment of 1, exhibited a higher activity with respect to 1 in all the biological assays. Then an
increased ability of the 5 and 6 to inhibit NF-kB driven transcription may lead to a down-regulation of MMP-9 expression and secretion. This work provides new details about the structural requisites for NF-kB inhibitio
Determination of Aloesin and Aloeresin A for the detection of Aloe in Beverage
No full textThis work describes a sensitive high-performance liquid chromatography (HPLC) method for the quantification of aloesin and aloeresin A in alcoholic beverages containing aloe as a flavoring agent. The compounds were prepared from Aloe ferox juice. Sephadex LH20 and ion-exchange resin AG1X2 column chromatography were used for aloesin. Aloeresin A was obtained by Sephadex LH20 and silica gel column chromatography followed by purification on Discovery DSC-18 solid-phase extraction tubes. A 98 mg amount of aloesin (>99% purity) and 34 mg of aloeresin A (>98% purity) were recovered from 2.5 g of aloe juice. The HPLC method was validated, and intra- and interday performances were established. In-house validation was carried out by analyzing samples of beverages with and without aloe as a flavoring agent
Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase
No full textThe aim of the present study was to confirm that olive oil phenols reduce human platelet aggregability and to verify the hypothesis that cAMP- and cGMP- phosphodiesterases (PDE) could be one of the targets of the biological effect. Four extracts from oils characterized by a high phenol content (HPE), and low phenol levels (LPE) were prepared and analyzed quali- and quantitatively by HPLC-UV and electrospray ionization - MS/MS. Human washed platelets stimulated with thrombin were used for the aggregation assay. Human platelet cAMP-PDE and recombinant PDE5A1 were used as enzyme source. Platelet aggregation and enzyme activity were assayed in the presence of HPE, LPE and individual phenols. The phenol content of HPE ranged between 250 and 500 mg/kg, whereas the LPE content was 46 mg/kg. The compounds identified were hydroxytyrosol (HT), tyrosol (TY), oleuropein aglycone (OleA) and the flavonoids quercetin (QU), luteolin (LU) and apigenin (AP). OleA was the most abundant phenol (range 23.3 to 37.7 %) and LU was the most abundant flavonoid in the extracts. Oil extracts inhibited platelet aggregation with an 50% inhibitory concentration interval of 1.23 -11.2 μg/ml. The inhibitory effect of individual compounds (10 μ m) including homovanillyl alcohol (HVA) followed this order: OleA > LU > HT = TY = QU = HVA, while AP was inactive. All the extracts inhibited cAMP-PDE, while no significant inhibition of PDE5A1 (50 μg/ml) was observed. All the flavonoids and OleA inhibited cAMP-PDE, whereas HT, TY, HVA (100 μm) were inactive. Olive oil extracts and part of its phenolic constituents inhibit platelet aggregation; cAMP-PDE inhibition is one mechanism through which olive oil phenols inhibit platelet aggregation
Anti-plasmodial activity of Ailanthus excelsa
Full text linkThe anti-plasmodial activity of Ailanthus excelsa stem bark was investigated. The methanolic extract inhibited in vitro growth of chloroquine-sensitive (D10) and resistant strains (W2) of Plasmodium falciparum (IC50 4.6 and 2.8 μg/ml, respectively). The effect was retained in the chloroform fraction (3.1 and 2.1 μg/ml, respectively). The anti-plasmodial activity could be ascribed to the impairment of haemoglobin degradation through the inhibition of plasmepsin II activity (IC50 of 13.43 ± 1.74 μg/ml) and of the haem detoxification to haemozoin
Metformin improves peripheral vascular flow in nonhyperlipidemic patients with arterial disease
No full textThe clinical activity of metformin (N, N-dimethyl biguanide), a widely used antidiabetic agent, on arterial blood flow was evaluated in 15 patients with peripheral atherosclerosis. Flow was determined by quantitative strain-gauge plethysmography; plasma lipid, lipoprotein, and apoprotein levels were repeatedly tested during the cross-over trial, comparing 6 months of drug and placebo administration. Metformin (850 mg tid) significantly increased arterial flow after a standardized ischemia (+ 17.3% after 3 months and + 40.0% after 6 months). The increase in arterial flow was reversible after the switch to placebo was made. The drug was similarly effective, although to a lesser extent (+ 18.6% after 6 months), when given after the placebo. A highly significant effect of drug treatment, as well as of the sequence of administration, could be established by analysis of variance. In spite of the minimal changes of plasma lipid levels during metformin, a highly significant increase of high density lipoprotein cholesterol (+ 8.3% during the whole treatment) was demonstrated; plasma levels of isoprotein AI-1 were also raised during the metformin period. This controlled experiment confirms data from previous open studies, as well as from a longstanding clinical experience. Although the mechanism of the metformin effect cannot, at present, be defined, the reported results indicate that treatments not markedly affecting plasma lipid-lipoprotein levels may improve vascular function in selected arterial districts
Gli ellagitannini di Punica granatum antagonizzano la risposta immune innata nella malaria
No full textIl pericarpo del frutto immaturo di Punica granatum (P.g.) L. è usato in una formulazione per la terapia e la profilassi malarica in Orissa, una regione dell’India. La malaria cerebrale è una complicanza grave dovuta alla citoaderenza di Plasmodium falciparum ai vasi cerebrali e all’eccesso di risposta infiammatoria, associata ad una sovraproduzione di mediatori tra cui metalloproteasi-9 (MMP-9) e TNF. Studi recenti hanno dimostrato l’attività antiplasmodio di P.g. in vitro [1]. Lo scopo del presente studio è stato di esplorare se oltre all’effetto antimalarico, P.g. potesse modulare la risposta immune dell’ospite. A tal fine si è preparata una frazione arricchita in tannini (P.g.-FRT) dall’estratto metanolico del pericarpo. L’espressione genica e la secrezione di MMP-9 sono state valutate in cellule THP-1 stimolate con il pigmento malarico (emozoina, 6 μg/ml). Per valutare se i meccanismi molecolari alla base dell’effetto coinvolgessero il fattore nucleare di trascrizione NF-kB, abbiamo valutato l’effetto delle molecole sul promotore di NF-kB in seguito a stimolo con emozoina. I saggi sono stati condotti su P.g.-FRT e sui costituenti principali della frazione: acido ellagico e punicalagina. Inoltre, è stato valutato anche l’effetto delle urolitine, i metaboliti intestinali degli ellagitannini. P.g.-FRT (50 e 100 μg/ml) inibisce la secrezione di MMP-9 indotta da emozoina rispettivamente del 78% e 95%; l’effetto osservato è ascrivibile alla presenza di punicalagina e acido ellagico poichè tali sostanze riducono la secrezione dell’enzima rispettivamente del 79% e 66% a 10 μM. L’effetto osservato sulla secrezione di MMP-9 sembra essere dovuto ad una diminuzione dell’espressione genica in quanto FRT e i composti puri, alle medesime concentrazioni, diminuiscono i livelli di mRNA di MMP-9 e inibiscono l’attività del promotore di MMP-9. Anche le urolitine (25 μM) inibiscono l’espressione e la secrezione di MMP-9. FRT, acido ellagico e punicalagina riducono l’attività del promotore di NF-kB, suggerendo un coinvolgimento di questo fattore di trascrizione nei meccanismi alla base dell’attività biologica osservata.
Gli effetti benefici del pericarpo di P.g. nel trattamento della malaria sono quindi in relazione sia all’attività diretta sul parassita sia all’inibizione di uno dei meccanismi pro-infiammatori coinvolti nell’insorgenza della malaria cerebrale. Riferimenti [1] M. Dell’Agli, G.V. Galli, Y. Corbett, D. Taramelli, L. Lucantoni, A. Habluetzel, O. Maschi, D. Caruso, S. Giavarini, S. Romeo, D. Bhattacharya, E. Bosisio Journal of Ethnopharmacology, 2009, 125, pag. 27
Minor polar components of extra-virgin olive oil: inhibition of NF-kB activity at gastric level
No full textThe transcription factor modulates the expression of several genes involved in the inflammatory process and several studies demonstrate its involvement in gastritis and peptic ulcer, in the presence or not of the bacterium H. pylori infection. In vivo studies show that the minor polar components of extra-virgin olive oil possess anti-inflammatory properties. The aim of this work was to investigate the mechanism of action of the anti-inflammatory effect, by evaluating whether the phenolic extract from extra-virgin olive oil inhibited the NF-kB driven transcription in gastric adenocarcinoma cells (AGS), and assessing the contribution of individual phenols.
Phenolic extracts were obtained from two commercial extra-virgin olive oils, respectively from Italy and Spain, by extraction with MeOH:H2O, 80:20 v:v, and quantified with Folin-Ciocalteu assay. Secoiridoids (oleuropein aglycone and ligustroside aglycone) were analyzed by LC-MS, and phenolic alcohols (tyrosol and hydroxytyrosol) by GC-MS. AGS cells were transfected with luciferase reporter plasmid and stimulated with TNF as a pro-inflammatory agent. Both phenolic extracts inhibited NF-kB activity in a concentration-dependent manner (IC50 of 0.86 ± 0.12 μg/ml, and 1.28 ± 0.13 μg/ml for the Italian and Spanish oil respectively; mean + sd). Secoiridoids represented over the 70% of the phenolic extracts while phenolic alcohols corresponded to less than 7%. All individual compounds inhibited the activity of NF-kB in a statistically significant manner (-50% at 10 μM). Since hydroxytyrosol is catabolized to homovanillic alcohol by catechol-o-methyltransferase in humans, the effect of the later was also evaluated even if not present in the oil. The inhibitory effect reached statistically significant values at 1 μM. The effect of the two phenolic extracts was then compared to the reconstituted mixtures of the four constituents. Ligustroside aglycone and oleuropein aglycone, not commercially available, were prepared from their glucosides by hydrolysis with β-glucosidase. Reconstituted mixtures had an inhibitory effect comparable to that of the total phenolic extracts, indicating that the compounds are the main responsible of the activity of the extract.
In conclusion, the results of this study suggest that the anti-inflammatory effect of the polar fraction of extra-virgin olive oil may be mediated by the inhibition of NF-kB activity. The concentration at which the phenolic extracts are active are compatible with a consumption of 30-50 g/die of oil, as estimated in the Mediterranean dietary regimen. Secoiridoids and phenolic alcohols, as well as homovanillic alcohol, contribute to anti-inflammatory action in gastric cells
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