Inhibition Of Platelet-activating Factor Research Articles

Does Yogurt Enriched with Platelet-Activating Factor Inhibitors from Olive Oil By-Products Affect Gut Microbiota and Faecal Metabolites in Healthy Overweight Subjects? (A randomized, parallel, three arm trial.).

The effect of the daily consumption of a low-fat yogurt (150 g) enriched with Platelet-Activating Factor receptor (PAF-R) antagonists, or the plain one, on gut microbiota and faecal metabolites was investigated in healthy overweight subjects. A randomized, three-arm, double-blind, placebo-controlled, parallel-group study was performed that lasted 8 weeks. Blood and stools were collected and analyzed before and after the intervention. Our findings revealed that the intake of the enriched yogurt resulted in a significant increase in the levels of Bifidobacterium spp., Clostridium perfringens group and Firmicutes-to-Bacteroidetes (F/B) ratio. On the other hand, a significant increase in the levels of Lactobacillus and C. perfringens group was detected after the intake of the plain yogurt. The increase in the levels of C. perfringens group was inversely associated with the plasma catabolic enzyme of PAF, namely LpPLA2 (lipoprotein-associated phospholipase A2), a cardiovascular risk marker that has been linked with inflammation and atherosclerosis. Moreover, in the enriched with PAF-R antagonists yogurt group, the increased levels of C. perfringens group were also associated with lower PAF action assessed as ex vivo human platelet-rich plasma (PRP) aggregation. Additionally, a higher % increase in molar ratio of Branched Short Chain Fatty Acids (BSCFAs) was detected for both yogurt groups after the 8 week-intervention compared to control. The consumption of the enriched yogurt also resulted in a significant drop in faecal caproic levels and a trend for lower ratio of butyrate to total volatile fatty acids (VFAs) compared to baseline levels. Yogurt consumption seems to favorably affect gut microbiota while its enrichment with PAF-R antagonists from olive oil by-products, may provide further benefits in healthy overweight subjects. ClinicalTrials.gov (NCT02259205).

Effect of Fortification of Tahini with Natural Plant Origin Raw Materials on Its Bioactivity

Food fortification is a strategic approach to enhance the nutritional quality of food by incorporating bioactive compounds derived from food by-products. The objective of this study was to assess the impact on bioactivity of tahini enriched with a 4% (w/w) lyophilized microwave-ultrasound assisted extract of red grape pomace from the Limnio variety and a 6% (w/w) freeze-dried aquafaba obtained from Lemnian chickpeas of the Panagia variety. The evaluation was conducted through in vitro experiments. The samples under study were extracted by the Bligh and Dyer method and analyzed for their polyphenolic content, as well as for their content in total flavonoids. Assessment of the antioxidant capacity of the extracts was determined in vitro by the ABTS, DPPH, CUPRAC, FRAP and human blood plasma oxidation inhibition (hBPOxi) assays, while the antiplatelet activity of the extracts was determined by the Platelet Activating Factor inhibition assay (PAFi). The bioactivity of fortified tahini (LAC) was increased compared to plain tahini (Control sample). Total phenolics and total flavonoids were increased by 76% and 78%, respectively (10.7 ± 0.2 vs. 6.02 ± 0.3 and 8.5 ± 0.14 vs. 4.76 ± 0.1 μmol Trolox/g, respectively). Antioxidant activities based on ABTS, DPPH, CUPRAC, FRAP and hBPOxi were increased by 101%, 65%, 77%, 73% and 110%, respectively (52.8 ± 0.7 vs. 26.3 ± 0.4; 20.1 ± 1.6 vs. 12.2 ± 0.2; 81.9 ± 0.4 vs. 46.1 ± 2.1; 46.4 ± 4.0 vs. 26.8 ± 0.8; and 12.2 ± 0.9 vs. 5.8 ± 0.2 μmol Trolox/g, respectively), and antiplatelet activity based on PAFi was also increased by 41% (0.19 ± 0.01 vs. 0.32 ± 0.02 mg, respectively). Red grape pomace extract and aquafaba boosted tahini’s in vitro antioxidant and antiplatelet capabilities. The results indicate that the valorization of grape and chickpea processing residuals may reduce waste and improve the nutritional value of tahini. Due to its antioxidant and antiplatelet activities, fortified tahini may contribute to the prevention of chronic diseases where oxidation and thrombosis play critical roles. This study exemplifies sustainable resource use and waste reduction, as well as the importance of circular economy strategies in enhancing diets and human welfare.

Protective Effect of Olive Oil Microconstituents in Atherosclerosis: Emphasis on PAF Implicated Atherosclerosis Theory.

Atherosclerosis is a progressive vascular multifactorial process. The mechanisms underlining the initiating event of atheromatous plaque formation are inflammation and oxidation. Among the modifiable risk factors for cardiovascular diseases, diet and especially the Mediterranean diet (MedDiet), has been widely recognized as one of the healthiest dietary patterns. Olive oil (OO), the main source of the fatty components of the MedDiet is superior to the other "Mono-unsaturated fatty acids containing oils" due to the existence of specific microconstituents. In this review, the effects of OO microconstituents in atherosclerosis, based on data from in vitro and in vivo studies with special attention on their inhibitory activity against PAF (Platelet-Activating Factor) actions, are presented and critically discussed. In conclusion, we propose that the anti-atherogenic effect of OO is attributed to the synergistic action of its microconstituents, mainly polar lipids that act as PAF inhibitors, specific polyphenols and α-tocopherol that also exert anti-PAF activity. This beneficial effect, also mediated through anti-PAF action, can occur from microconstituents extracted from olive pomace, a toxic by-product of the OO production process that constitutes a significant ecological problem. Daily intake of moderate amounts of OO consumed in the context of a balanced diet is significant for healthy adults.

Lipopolysaccharide Priming Exacerbates Anaphylatoxin C5a-Induced Anaphylaxis in Mice.

Anaphylaxis is a serious allergic or hypersensitivity reaction with a sudden onset that can be life-threatening or fatal. Previous studies have highlighted two pathways of anaphylaxis in mice. One is the classical immunoglobulin E (IgE)-mediated pathway that involves mast cells and histamine. The other is an alternative IgG-mediated pathway that involves basophils, monocytes/macrophages, neutrophils, and the platelet-activating factor (PAF). However, little is known about the mechanism by which complement anaphylatoxins contribute to the induction of anaphylaxis. Infection is a cofactor that potentially amplifies the risk of anaphylaxis. Here, we showed that priming with a lipopolysaccharide (LPS), which mimics bacterial infection, exacerbates anaphylatoxin C5a-induced anaphylaxis in mice. LPS plus C5a-induced anaphylaxis was mediated by histamine and lipid mediators, especially PAF. Cell depletion experiments demonstrated that LPS plus C5a-induced anaphylaxis depended on monocytes/macrophages, basophils, and neutrophils. These results suggest that C5a is a potent inducer of anaphylaxis in bacterial infections. Remarkably, the molecular and cellular mediators of LPS plus C5a-induced anaphylaxis are mostly shared with IgE- and IgG-mediated anaphylaxis. Therefore, combined inhibition of histamine and PAF may be beneficial as a second-line treatment for severe anaphylaxis.

Treatment of Microcirculatory Disturbances in Acute Pancreatitis: Where Are We Now?

Acute pancreatitis is a serious inflammatory condition. Research has shown an increase in the number of pancreatitis-associated hospitalizations, with a marked decline in the mortality rates down to 0.79% in patients with acute pancreatitis and 0.26% in patients with exacerbation of chronic pancreatitis. Up to one-third of patients develop pancreatic tissue necrosis, with a mortality rate of 30%. One of the mechanisms is the disturbances in pancreatic microcirculation due to the release of endothelin, a long-acting vasoconstrictor. The development of pancreatitis causes the release of other inflammatory mediators, which reduce blood flow in the microcirculation. The activation of intracellular trypsinogen initiates a cascade of mechanisms in pancreatitis. There is no specific treatment for acute pancreatitis. Protease inhibitors are not effective in treating severe acute pancreatitis. There is an important role of low-molecular-weight heparin in attenuating necrosis and restoring perfusion of the pancreas. Other drugs used are endothelin receptor antagonists, antagonist of interleukin-1 and interleukin-6 receptors, α-tocopherol, tumor necrosis factor-α and platelet-activating factor inhibitors, acetylsalicylic acid, and local intra-arterial injection of lidocaine. The prophylactic use of antibiotics is not recommended. The treatment outcome of acute pancreatitis is still unsatisfactory.

Inhibition of platelet-activating factor (PAF)-induced platelet aggregation by fatty acids from human saliva

Experiments were undertaken to identify the nature of a previously identified inhibitor of PAF-induced platelet aggregation (PA) in human saliva. Human saliva fractionated by preparative thin layer chromatography (TLC) yielded a fraction that co-migrated with fatty acids (FAs) and inhibited PAF-induced aggregation of platelets. Synthetic FAs tested for their capacities to inhibit 0.1 nM PAF-induced PA showed that only the cis-unsaturated compounds were inhibitory with activities of some of the polyunsaturated FAs (PUFA) reaching almost 100% at 20 μM. Eicosapentanoic acid EPA and 8,11,14-eicosatrienoic acid also deaggregated the PAF-induced aggregates. With the exception of oleic acid (OLA), cis-monounsaturated FAs, and elaidic acid, the trans isomer of OLA, were poor inhibitors. In a direct comparison with other platelet agonists, ADP, thrombin, and ionophore A23187, the active saliva fraction and selected individual FA inhibited, to greater or lesser extent, PA induced by each of the agonists. EPA, OLA, linoleic acid (LNA), and the active saliva fraction were potent inhibitors of ADP-induced PA, EPA completely inhibited thrombin-induced PA and the saliva fraction showed only weak – moderate inhibitory activity to both thrombin- and ionophore A23187-induced PA. Other reports of endogenous PAF inhibitors in mammalian tissues are compared to the present results. PAF can trigger and amplify inflammatory cascades suggesting a possible modulation role for cis-unsaturated FAs in some diseases.

Activities of platelet-activating factor (PAF) enzymes after daily consumption for two months of a yogurt enriched with natural origin PAF inhibitors

Background and Aims: Platelet-activating factor (PAF), a pro-inflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study is to evaluate the impact of a new functional yogurt enriched with natural origin PAF inhibitors from olive oil by-products on PAF metabolism.

Consumption of Enriched Yogurt with PAF Inhibitors from Olive Pomace Affects the Major Enzymes of PAF Metabolism: A Randomized, Double Blind, Three Arm Trial

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.

Molecular Docking, Drug likeness Studies and ADMET prediction of Flavonoids as Platelet-Activating Factor (PAF) Receptor Binding

Studies and scientific research indicate that the platelet-activating factor (PAF) is a major pro-inflammatory mediator in the initiation and development of cancer. There is also evidence confirming that PAF is an integral part of suppressing the immune system and promoting the appearance of a malignant tumor. For this reason, it is useful to analyze the molecular docking data of eleven flavonoids derivatives isolated from the active leaf extracted from chromolaena odorata with their anti-PAF activity. As a result, it is evident that the natural product of flavonoids may have a positive effect in the development of both therapeutic and preventive agents for platelet activating factor (PAF) antagonist and suggests potential guidelines for the design of PAF inhibitors. Based on the docking score analysis, drug likeness study, and ADMET prediction. We found that six compounds respect all drug-likeness rules and can be used as a potent molecule for inhibition of platelet activating factor (PAF).

Luteolin and apigenin derived glycosides from Alphonsea elliptica abrogate LPS-induced inflammatory responses in human plasma

Ethnopharmacological relevanceNumerous Alphonsea species including Alphonsea elliptica (mempisang) leaves and fruits are indigenously used in inflammatory conditions such as postpartum swelling and rheumatism in southeast Asian countries. In our previous in-vitro findings, A. elliptica methanol extract exhibited platelet-activating factor inhibition, suggesting the presence of phyto-constituents with anti-inflammatory potential. Aim of the studyHowever, so far there is no literature available on the anti-inflammatory activity of this species. Henceforth, based on the above background and our previous laboratory findings, we hypothesize that phytoconstituents of A. elliptica could possess anti-inflammatory potential against inflammatory mediators including prostaglandin-E2 (PGE2), cyclooxegenase-2 (COX-2) and cytokines (IL-1β and IL-6). Materials and methodsVacuum and column chromatography techniques were employed for the isolation of phytoconstituents. The structure elucidation was carried out using HRESI-MS, 1H and 13C-NMR analysis and compared with the published literature. For cytotoxicity analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed on peripheral blood mononuclear cells. In-vitro anti-inflammatory activities were evaluated against the levels of PGE2, COX-2, IL-1β and IL-6 in lipopolysaccharide (LPS)-induced human plasma using enzyme-linked immunosorbent assay and radioimmunoassay. ResultsUnprecedentedly, chromatographic purification of methanolic leaves extract afforded five flavones namely vitexin, isovitexin, orientin, isoorientin, schaftoside with three flavanols; kaempferol, myricetin and rutin from A elliptica. In cell viability analysis, isolates did not present cytotoxicity up to 50 μM. In anti-inflammatory evaluation, orientin and isoorientin exhibited strong (≥70%), while isovitexin and vitexin produced strong to moderate (50–69%) PGE2, COX-2, IL-1β and IL-6 inhibition at 25 and 50 μM. Isoorientin, orientin, isovitexin, and vitexin showed significant (p < 0.05) and concentration-dependent PGE2 inhibition with IC50 values (μM) of 11.40, 14.71, 17.70 and 20.58 against indomethacin (8.80). Furthermore, isoorientin, orientin, isovitexin, and vitexin produced significant concentration-dependent inhibition with IC50 values (μM) of COX-2: 7.13, 9.51, 12.81, 16.61; IL-1β 4.80, 6.20, 10.85, 14.51; IL-6: 4.01, 5.90, 11.51 and 14.88 as compared to dexamethasone: 5.29, 2.93, 3.72, respectively (p < 0.05). ConclusionConclusively, isolated phytoconstituents are reported for the first time from the A. elliptica. Moreover, isovitexin, vitexin orientin and isoorientin abrogated LPS-induced inflammatory responses in human plasma at non-cytotoxic concentrations.

A new prenylated benzoquinone from Cyathocalyx pruniferus abrogates LPS-induced inflammatory responses associated with PGE2, COX-2 and cytokines biosynthesis in human plasma.

In our previous laboratory findings, Cyathocalyxpruniferus extracts exhibited platelet-activating factor inhibition, suggesting their anti-inflammatory potential. Hence, this study was designed with the aim to isolate phyto-constituents from C. pruniferus with potent anti-inflammatory activities. Column and volume liquid chromatography were used for isolation of phyto-constituents. The structure elucidation was carried out using spectroscopic analysis (HRESI-MS, 1H and 13C-NMR) and compared with published literature. For cytotoxicity analysis, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay was performed on peripheral blood mononuclear cells. Anti-inflammatory activities were evaluated against the levels of inflammatory cytokines (IL-1β and IL-6), prostaglandin-E2 (PGE2) and cyclooxegenase-2 (COX-2), in lipopolysaccharide (LPS)-induced human plasma using ELISA and radioimmunoassay (RIA). The chromatographic purification of methanol leaves extract afforded 13 (1-13) secondary metabolites. Additionally, cytotoxicity analysis suggested that isolates were non-cytotoxic at 100μM. In anti-inflammatory evaluation, 2-octaprenyl-1, 4-benzoquinone (5) produced strong (≥ 70%) inhibition of PGE2, COX-2, IL-1β and IL-6 at 50µM. Moreover, 2-octaprenyl-1,4-benzoquinone (5) exhibited concentration-dependent inhibition with IC50 values (µM) of 11.21, 6.61, 2.20 and 3.56 as compared to controls; indomethacin for PGE2 (11.84) and dexamethasone in COX-2 (5.19), IL-1β (1.83) and IL-6 (3.76) analysis, respectively. In conclusion, two new compounds including 2-octaprenyl-1, 4-benzoquinone (5) and 14-methyloctadec-1-ene (6) are reported for the first time from plant species. Additionally, 2-octaprenyl-1, 4-benzoquinone (5) dose-dependently suppressed the production of pro-inflammatory mediators involved in acute and chronic inflammation at non-cytotoxic concentrations.

Antithrombotic and antiplatelet activity of an organometallic rhodium(I) complex incorporating a substituted thieno‐[2,3‐d]‐pyrimidine ligand: Synthesis, structural characterization, and molecular docking calculations

The antiplatelet and antithrombotic activity of a novel organometallic rhodium(I) complex of the formula [Rh(cod)Cl(tpc)] (1) (cod = cis‐1,5‐cyclooctadiene; tpc = methyl 2‐amino‐4‐(diethylamino)‐thieno‐[2,3‐d]‐pyrimidine‐6‐carboxylate) was investigated. Complex 1 was easily synthesized by a one‐pot, high‐yield reaction and was fully characterized by standard spectroscopic techniques including FT‐IR, UV–Vis, and NMR spectroscopy and by elemental analysis. The molecular structures of tpc and 1 were determined by single‐crystal X‐ray crystallography. Complex 1 displayed a slightly distorted square planar geometry and is the first crystallographically characterized example of a coordination compound bearing the ligand precursor tpc. Biological studies demonstrate that 1 displays strong antiplatelet and antithrombotic properties in vitro, by inhibiting both the aggregation of human and washed rabbit platelets induced by the potent inflammatory and thrombotic mediator, platelet‐activating factor (PAF) in the micromolar range. This is an approach of continuous interest in the field. Molecular docking calculations suggest that 1 can fit at the ligand‐binding site of the PAF receptor (PAFR) and thus block PAF thrombotic activities, through an antagonistic effect on the PAF/PAFR‐related pathway, which is in accord with the experimental findings. Complex 1 constitutes an interesting example of a metal‐based PAF inhibitor with promising antiplatelet, antithrombotic, and anti‐inflammatory activity, because PAF is the most potent inflammatory lipid mediator. This is also supported by the fact that 1 is an inhibitor of other inflammatory and thrombotic mediators like thrombin, along with well‐established platelet agonists like ADP and collagen.

Identifying key components and therapeutic targets of the immune system in hidradenitis suppurativa with an emphasis on neutrophils.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent and debilitating skin disease of the hair follicle unit that typically develops after puberty. The disorder is characterized by comedones, painful inflammatory nodules, abscesses, dermal tunnels and scarring, with a predilection for intertriginous areas of the body (axillae, inguinal and anogenital regions). Recruitment of neutrophils to HS lesion sites may play an essential role in the development of the painful inflammatory nodules and abscesses that characterize the disease. This is a review of the major mediators involved in the recruitment of neutrophils to sites of active inflammation, including bacterial components (endotoxins, exotoxins, capsule fragments, etc.), the complement pathway anaphylatoxins C3a and C5a, tumour necrosis factor-alpha, interleukin (IL)-17, IL-8 (CXCL8), IL-36, IL-1, lipocalin-2, leukotriene B4, platelet-activating factor, kallikreins, matrix metalloproteinases, and myeloperoxidase inhibitors. Pharmacological manipulation of the various pathways involved in the process of neutrophil recruitment and activation could allow for successful control and stabilization of HS lesions and the remission of active, severe flares.

Micronutrients, Phytochemicals and Mediterranean Diet: A Potential Protective Role against COVID-19 through Modulation of PAF Actions and Metabolism.

The new coronavirus disease 2019 (COVID-19) pandemic is an emerging situation with high rates of morbidity and mortality, in the pathophysiology of which inflammation and thrombosis are implicated. The disease is directly connected to the nutritional status of patients and a well-balanced diet is recommended by official sources. Recently, the role of platelet activating factor (PAF) was suggested in the pathogenesis of COVID-19. In the present review several micronutrients (vitamin A, vitamin C, vitamin E, vitamin D, selenium, omega-3 fatty acids, and minerals), phytochemicals and Mediterranean diet compounds with potential anti-COVID activity are presented. We further underline that the well-known anti-inflammatory and anti-thrombotic actions of the investigated nutrients and/or holistic dietary schemes, such as the Mediterranean diet, are also mediated through PAF. In conclusion, there is no single food to prevent coronavirus Although the relationship between PAF and COVID-19 is not robust, a healthy diet containing PAF inhibitors may target both inflammation and thrombosis and prevent the deleterious effects of COVID-19. The next step is the experimental confirmation or not of the PAF-COVID-19 hypothesis.

Yoghurt fermentation alters the composition and antiplatelet properties of milk polar lipids.

Dairy polar lipids (PL) seem to exhibit antiplatelet effects. However, it is not known what molecular species may be responsible. In this study, we confirmed using C30 reversed-phase (C30RP) ultra-high-performance liquid chromatography (UHPLC) coupled to high resolution accurate mass tandem mass spectrometry (HRAM-MS/MS) that fermentation of yoghurts from ovine milk using specific starter cultures altered the PL composition. These lipid alterations occurred concomitant with increased antithrombotic properties of the yoghurts PL fractions against platelet-activating factor (PAF) and thrombin-induced platelet aggregation. Specifically, elevation in phosphatidylethanolamine (PE), sphingomyelin (SM), phosphatidylcholine (PC) and their molecular species were observed following yoghurt fermentation. Furthermore, PC(18:0/18:1), PE(18:1/18:2), SM(d18:0/22:0) and several other molecular species were significantly inversely correlated with the inhibition of PAF and thrombin. These molecular species were abundant in the most bioactive yoghurts fermented by S. thermophilus and L. acidophilus, which suggest that fermentation by these microorganisms increases the antithrombotic properties of ovine milk PL.

Exposure to Cigarette Smoke is Linked to Platelet‐Activating Factor Accumulation in Myocardial Tissue

Smoking is a lifestyle risk factor for heart disease and is responsible for one‐third of all cardiovascular deaths. Although many studies have investigated the correlation between smoking and coronary artery disease, there are few studies examining the direct effect of smoking on the myocardium. In this study, we examined the effect of smoking on myocardial accumulation of platelet‐activating factor (PAF), a phospholipid mediator that causes a negative inotropic effect, arrhythmias, apoptosis and is involved in inflammation and atherosclerosis. Ventricular samples from mice exposed up to six months of cigarette smoke (48 min/day, 5 days/week), and human right atrial samples from smokers and nonsmokers scheduled for coronary artery bypass graft surgery were analyzed for biochemical and histochemical changes using activity assays, ELISA, immunoblot, and immunohistochemistry. Mice exposed to cigarette smoke showed a decrease in PAF‐acetylhydrolase (PAF‐AH, the enzyme responsible for PAF metabolism) activity that was significant after 1 month and decreased progressively over the 6 month period (5.8 ± 0.3 to 3.2 ± 0.5 nmol/mg protein/min, p&lt;0.01, n=6). This inhibition in PAF‐AH activity was accompanied by increased myocardial PAF content (0.23 ± 0.04 to 0.35 ± 0.03 at 6 months smoking, p&lt;0.05, n=6). In humans, smoking was associated with an increase in PAF content (3.19 ± 0.28 vs 4.29 ± 0.37 nmol/mg protein, p&lt;0.05, n=18) and inhibition of PAF‐AH activity (30.7 ± 2.0 vs 23.2 ± 1.8 nmol/mg protein/min, p&lt;0.01, n=18) when comparing atrial tissue from never smokers to current smokers. We did not detect a change in phospholipase A2 activity (the enzyme responsible for PAF production) in human or mouse myocardium exposed to cigarette smoke or room air. Thus, we hypothesize that the increase in PAF content in the myocardium is likely a result of smoking‐induced inhibition of PAF‐AH activity. The inhibition of PAF‐AH and subsequent accumulation of PAF in the myocardium of cigarette smokers may play a role in the pathogenesis of heart disease in this population.Support or Funding InformationLottie Caroline Hardy Foundation (to J.McH.)

Substituted pyridine-quinoline ligands as building blocks for neutral rhodium(III) complexes. Synthesis, structural characterization studies and anti-platelet activity towards the Platelet-Activating Factor (PAF)

The Friedländer condensation reaction was employed to synthesize the new bidentate ligands namely 6-bromo-4-phenyl-2-pyridin-2-yl-quinoline (1) and 4-(4-phenyl-2-(pyridin-2-yl)quinolin-6-yl)phenol (2). These compounds were fully characterized including the X-ray structures of 1 and the protonated form of 2, i.e. 2·HCl·H2O. We also report the synthesis and spectroscopic characterization of two rhodium(III) complexes of the general formula [Rh(1)Cl3(CH3OH)] (3) and [Rh(2)Cl3(CH3OH)] (4). The molecular structures of 3·2CH3OH and 4 were determined by single-crystal X-ray diffraction studies, revealing that these complexes adopt the mer-configuration. The solution stability of 3, 4 was studied by a combination of UV–Vis and 1H NMR spectroscopic techniques. All compounds were biologically evaluated for their anti- platelet activity using their potency to inhibit the action of PAF (Platelet-Activating Factor), which is an approach of continuous interest in the field. Complexes 3 and 4 were found to be potent PAF inhibitors with IC50 values in the micromolar range (1.0 μM and 3.9 μM respectively). Since PAF is the most potent inflammatory lipid mediator, the PAF-inhibitors and consequently the title compounds may be considered as potent examples in the search for novel anti-inflammatory drugs.

Cardioprotective properties of a novel enriched yogurt with inhibitors of Platelet Activating Factor (PAF)

AbstractPlatelet Activating Factor (PAF) is a pro-inflammatory mediator of atherogenesis. Food enriched with PAF inhibitors may have potential cardioprotective properties. In this attempt our group along with a well-known Greek dairy company incorporated bioactive ingredients (BAL) from olive-oil by-products, rich in PAF receptor specific inhibitors, into another typical food of the Mediterranean diet, namely yogurt. The aim of the present study was to evaluate the cardioprotective properties of the enriched yogurt in apparently healthy volunteers.Ninety two apparently healthy volunteers (35–65 years) were randomly allocated into three groups by block-randomization based on age, sex and BMI. The volunteers in Group A did not consume any yogurt. The volunteers of Group B consumed a non-enriched yogurt daily. The Group C volunteers ate daily an enriched yogurt. The intervention lasted 8 weeks. Volunteers’ adherence to the study protocol was assessed by two 24 h recalls every two weeks conducted by trained personnel. Blood and urine samples were collected at baseline, at 4th week and at 8th week of the intervention and biochemical and inflammatory markers were determined. In addition, platelet aggregation in volunteers’ platelet rich plasma against PAF, ADP and TRAP were measured and the results expressed as the concentration of the agonist that cause 50% of the maximum aggregation (EC50, efficient concentration fifty values).Among classical anthropometric and biochemical markers, only a decrease of blood pressure (systolic and diastolic) levels was observed (p0–8weeks &lt; 0.05) in group B but with no clinical significance. Reduced levels of IL-10 was observed in group C compared to B both in the meantime (p4weeks = 0.01) and at the end of the intervention (p8weeks = 0.04). Furthermore, platelet sensitivity against PAF was only decreased (higher EC50 PAF,) in group C (p0–4weeks = 0.005 and p0–8weeks = 0.05). A trial effect was observed in the meantime among the three groups (p = 0.03).The consumption of the enriched yogurt led to attenuation of subclinical inflammation and platelet sensitivity to thrombotic stimuli in apparently healthy volunteers, indicating a potential cardioprotective role of PAF inhibitors.The work is funded by SYNERGASIA 2011 PROGRAMME. This Programme is co-funded by the European Regional Development Fund and National Resources, Project Code 11SYN-2-652.

Cardioprotective properties of fish enriched with bioactive lipids from olive oil by products

AbstractAnti-inflammatory properties of olive oil are partly attributed to the inhibition of the Platelet-Activating Factor (PAF), a potent inflammatory mediator that is implicated in the initiation and prolongation of atherosclerosis. PAF inhibitors also exist in an extract from olive pomace that inhibits development and regression of atherosclerotic plaques in hypercholesterolemic rabbits. On the other hand, fish consumption is recommended for prevention of cardiovascular diseases, leading to a constantly increasing demand for fish supply, which is further enhanced by the rising consumers’ awareness. As a result a significant growth of aquaculture worldwide has been occurred, which among others strives for improving the nutritional value of the produced fish. Important breakthroughs have occurred in the replacement of fish oil, traditionally used, by plant oils in compounded fish feeds contributing to more nutritious fish products. Under this perspective, present work aimed to evaluate the cardioprotective properties of a novel seabream fed with olive pomace extract.In this crossover study, thirty apparently healthy, men and women were randomly assigned in two diet sequences for 8-week duration (6-week washout period between them), consuming either normal or enriched with olive pomace fish, twice a week. The study was approved by the Bioethics Committee of Harokopio University. Dietary intake was assessed with a validated for the Greek population semi-quantitative food-frequency questionnaire. Lifestyle parameters, biochemical factors, P-selectin and Plasminogen-activator inhibitor-1 (PAI-1) levels were determined. In addition, ex-vivo platelet aggregation in platelet-rich plasma against PAF, ADP and thrombin were measured and the results expressed as EC50 values (the concentration of the agonist that cause 50% of maximum aggregation). Also, PAF key metabolic enzymes activities, responsible for PAF levels, were determined.Concerning dietary habits and biochemical markers only total cholesterol revealed a small increase, within the normal range, after enriched fish consumption, compared to baseline levels. Both fishes resulted in higher EC50 (lower platelet sensitivity) values only against PAF without being differentiated (ptime = 0.02, ptrial = 0.9), while PAI-1 levels were only increased after normal fish consumption (p0–8 weeks = 0.01). The ratio of Lipoprotein-Associated-Phospholipase A2 (catabolic enzyme of PAF) to LDL and PAF-CDP-choline:cholinephosphotransferase (biosynthetic enzyme of PAF) were decreased after the enriched (p0–8 weeks = 0.003) and the normal (p0–8 weeks = 0.01) fish consumption, respectively.Seabream fed with olive pomace seems to exhibit cardioprotective properties by decreasing platelet sensitivity against PAF and modulate PAF metabolism.This research has been co-financed by the European Regional Development Fund of the EU and Greek national funds (project code:T1EDK-00687).

Platelet-Activating Factor (PAF) in Allergic Rhinitis: Clinical and Therapeutic Implications.

Platelet-activating factor (PAF) is a lipid mediator involved in several allergic reactions. It is released from multiple cells of the immune system, such as eosinophils, neutrophils, and mast cells, and also exerts its effect on most of them upon specific binding to its receptor, becoming a pleiotropic mediator. PAF is considered a potential relevant mediator in allergic rhinitis, with a key role in nasal congestion and rhinorrhoea due to its effect on vascular permeability. Interestingly, despite its potential relevance as a therapeutic target, no specific PAF inhibitors have been studied in humans. However, rupatadine, a second-generation antihistamine with dual antihistamine and anti-PAF effects has shown promising results by both blocking nasal symptoms and inhibiting mast cell activation induced by PAF, in comparison to antihistamine receptor drugs. In conclusion, the inhibition of PAF may be an interesting approach in the treatment of allergic rhinitis as part of a global strategy directed at blocking as many relevant inflammatory mediators as possible.