Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses.

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.

Antioxidant Activity of 3-[N-(Acylhydrazono)ethyl]-4-hydroxy-coumarins.

A series of 3-acylhydrazono-4-hydroxycoumarins were synthesized via condensation of 3-acetyl-4-hydroxycoumarin with appropriate hydrazides. The structures of the newly-synthesized compounds were characterized by spectral and elememental analysis or HRMS measurements. Their antioxidant properties were evaluated by using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as well as inhibition of lipid peroxidation. Moreover, their ability to inhibit in vitro soybean lipoxygenase has been investigated. They were found to be capable of rapid inactivation of alkylperoxy radicals.

Exploring the Relationship between Mediterranean Diet Adherence and Subjective Well-Being among Greek and Cypriot Adults.

Associations between subjective well-being (SWB) and dietary habits, employment status, and habitual activities are increasingly capturing the focus of researchers as well as policymakers worldwide. This study aimed to explore these associations in a sample of the population in Greece and Cyprus via an online survey. In total, 936 questionnaires (470: Cyprus, 466: Greece) were analyzed to study the associations between the Mediterranean Diet (MD) (using the 14-item MEDAS score, (14-MEDAS)), subjective well-being (SWB), and several socioeconomic factors. Key remarks of this survey highlight the positive impact of MD adherence on some well-being items. Namely, statistically significant differences were found on the following items: Satisfied with life (p < 0.001), Life worthwhile (p < 0.001), Feeling happy (p < 0.001), worried (p = 0.005), and depressed (p = 0.001), when comparing Low MD adherence (14-MEDAS < 5) to High MD adherence (14-MEDAS > 10). Other lifestyle habits such as spending time with friends and family, spending time in nature, and habitual physical activity were associated with aspects of SWB such as Life satisfaction, Life worthwhile, Feeling happy, and energetic. The findings support adherence to the MD, since it is associated with higher life satisfaction and self-reported happiness in this sample and should be considered when developing health policies on well-being.

Physical Activity, Body Mass Index (BMI) and Abdominal Obesity of Pre-Adolescent Children in the Region of Thrace, NE Greece, in Relation to Socio-Demographic Characteristics.

This study aimed to explore the prevalence of overweight, obesity, and abdominal obesity, and define predictive factors of their occurrence among pre-adolescents in the region of Thrace, NE Greece. A secondary aim was to record physical activity at different times (schooldays, weekends, holidays) and explore associations with characteristics such as gender, overweight and obesity, and socio-demographic conditions. A cross-sectional study was conducted involving children aged 11-12 years. Participating children were measured for height, weight, and waist circumference, and their parents answered a questionnaire. In total, 1929 children were included. Prevalence of overweight was 31.5%, prevalence of obesity 17%, and only 1% of children were underweight. Abdominal obesity was detected in 20.3% of the sample. Overweight and obesity were more frequent in males, who also had higher mean values of Body Mass Index-for-age z-scores (BMIaz) and Waist-to-Height ratio (WtHR). Obesity rates were higher among those not participating in physical activities; however, no significant difference was observed between normal-weight, overweight and obese children in the time spent for organized athletic activities or free play. Logistic regression analysis showed that the probability for overweight/obesity was higher in boys (OR = 1.39, 95% CI = 1.16-1.66) and lower in children whose fathers had a higher educational level (OR = 0.75, 95% CI = 0.60-0.93). The probability for abdominal obesity was also higher in boys (OR = 1.37, 95% CI = 1.10-1.72) and lower in children participating at least one hour/day in an organized physical activity (compared to those with no physical activity (OR = 0.66, 95% CI = 0.51-0.85), and whose father was exercising at least 1-2 times/week (OR = 0.76, 95% CI = 0.591-0.98). In conclusion, the prevalence of overweight and obesity among pre-adolescents in NE Greece was estimated at 48.5%. This is associated with the male gender and not participating in physical activities. The educational level and exercise habits of the father (but not of the mother) affect the probability of obesity and abdominal obesity, respectively.

Use of Edible, Medicinal, and Aromatic Plants in Various Health Disorders: A Cross-Sectional Evaluation among Inhabitants in the Area of Thrace, North-Eastern Greece.

BACKGROUND: Medicinal and aromatical plants (MAPs) have been historically used as traditional remedies in many cultures in Europe and globally. The aim of this study was to evaluate the use of MAPs in various health disorders in association to dietary habits and other lifestyle factors among residents in Thrace, NE Greece. METHODS: Data were collected through anonymous and voluntary responses to a structured online questionnaire, via convenience (snowball) sampling. RESULTS: The 561 responders (age: 39.7 ± 11.6 y) were mostly female (59.7%), with higher education (69.8%), working as state or private employees (55.4%), and having low/medium income (77.1%). Overall, more than 70% were using MAPs in various symptoms and common health disorders, such as chamomile against common cold and the flu. More than 20 different MAPs were being used in smaller frequencies against various conditions. Key contributing factors to the consumption of MAPs were sex (female over male), employment (employed vs. unemployed), education (higher education vs. lower) and higher Body Mass Index (overweight and obese vs. normal), while consumption of fruit, fish, and vegetables was mainly associated with the use of MAPs as common items of diet and in health disorders. CONCLUSIONS: The use of MAPs as part of the diet and as traditional remedy is present in the examined population, while particular choices seem to be affected by sociodemographic and lifestyle factors.

Exploring Hedonic and Eudaimonic Items of Well-Being in Mediterranean and Non-Mediterranean Countries: Influence of Sociodemographic and Lifestyle Factors.

Increased understanding of subjective well-being (SWB), as well as factors that influence it, are essential to enhance well-being at the individual and national level. We have applied a hedonic and eudaimonic 9-item composed tool (SWB score) to measure SWB across several Mediterranean (MED) and non-Mediterranean (non-MED) countries, and to explore the association between the SWB score and a range of sociodemographic, health and Mediterranean lifestyle factors. A specifically designed web-based questionnaire was distributed to adult participants (N = 2400) from Spain, Italy, Portugal, Bulgaria and Republic of North Macedonia. Results showed that the SWB score was significantly different across the examined countries with the MED participants displaying slightly higher average scores than the non-MED ones (6.3 ± 1.5 vs. 6.1 ± 1.6, p = 0.002). Several sociodemographic, health status and lifestyle factors displayed a significant but limited association with the 9-item SWB score, with a multiple regression model explaining around 17% of the variance. Nevertheless, our results support that a closer adherence to Mediterranean lifestyle habits-the Mediterranean Diet, spending time with friends, family, and in nature, being active, and getting adequate rest at night-has a positive influence on the 9-item SWB score. Further research is needed to advance the understanding of the measuring and differentiating of SWB across different populations and to establish all the factors that influence it.

Persistent Moderate-to-Weak Mediterranean Diet Adherence and Low Scoring for Plant-Based Foods across Several Southern European Countries: Are We Overlooking the Mediterranean Diet Recommendations?

The Mediterranean diet (MD) has been sponsored worldwide as a healthy and sustainable diet. Our aim was to update and compare MD adherence and food choices across several Southern European countries: Spain (SP), Portugal (PT), Italy (IT), Greece (GR), and Cyprus (CY) (MED, Mediterranean), and Bulgaria (BG) and the Republic of North Macedonia (NMK) (non-MED, non-Mediterranean). Participants (N = 3145, ≥18 y) completed a survey (MeDiWeB) with sociodemographic, anthropometric, and food questions (14-item Mediterranean Diet Adherence Screener, 14-MEDAS). The MED and non-MED populations showed moderate (7.08 ± 1.96) and weak (5.58 ± 1.82) MD adherence, respectively, with significant yet small differences across countries (SP > PT > GR > IT > CY > BG > NMK, p-value < 0.001). The MED participants scored higher than the non-MED ones for most of the Mediterranean-typical foods, with the greatest differences found for olive oil (OO) and white meat preference. In most countries, ≥70% of the participants reported quantities of red meat, butter, sweet drinks, and desserts below the recommended cutoff points, whereas <50% achieved the targets for plant-based foods, OO, fish, and wine. Being a woman and increasing age were associated with superior adherence (p-value < 0.001), but differences were rather small. Our results suggest that the campaigns carried out to support and reinforce the MD and to promote plant-based foods have limited success across Southern Europe, and that more hard-hitting strategies are needed.

A novel synthesis of 3-aryl coumarins and evaluation of their antioxidant and lipoxygenase inhibitory activity.

A series of coumarin analogues bearing a substituted phenyl ring on position 3 were synthesized via a novel methodology, through an intermolecular condensation reaction of 2-hydroxyacetophenones and 2-hydroxybenzaldehyde, with imidazolyl phenylacetic acid active intermediates. The in vitro antioxidant activity of the synthesized compounds was evaluated using two different antioxidant assays (radical scavenging ability of DPPH stable free radical and inhibition of lipid peroxidation induced by the thermal free radical AAPH). Moreover, the ability of the compounds to inhibit soybean lipoxygenase was determined as an indication of potential anti-inflammatory activity.

Exploring the Validity of the 14-Item Mediterranean Diet Adherence Screener (MEDAS): A Cross-National Study in Seven European Countries around the Mediterranean Region.

This study provides comprehensive validation of the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) in an adult population from Greece (GR), Portugal (PT), Italy (IT), Spain (SP), Cyprus (CY), Republic of North Macedonia (NMK), and Bulgaria (BG). A moderate association between the 14-MEDAS and the reference food diary was estimated for the entire population (Pearson r = 0.573, p-value < 0.001; Intraclass Correlation Coefficient (ICC) = 0.692, p-value < 0.001) with the strongest correlation found in GR, followed by PT, IT, SP, and CY. These results were supported by kappa statistics in GR, PT, IT, and SP with ≥50% of food items exhibiting a fair or better agreement. Bland-Altman analyses showed an overestimation of the 14-MEDAS score in the whole population (0.79 ± 1.81, 95%Confidence Interval (CI) 0.61, 0.96), but this value was variable across countries, with GR, NMK, and BG exhibiting the lowest bias. Taking all analyses together, the validation achieved slightly better results in the Mediterranean countries but a definitive validation ranking order was not evident. Considering growing evidence of the shift from Mediterranean Diet (MD) adherence and of the importance of culture in making food choices it is crucial that we further improve validation protocols with specific applications to compare MD adherence across countries.

Mediterranean Diet Adherence and Subjective Well-Being in a Sample of Portuguese Adults.

The Mediterranean diet (MD) and other lifestyle characteristics have been associated with well-being, a broad multiparameter concept that includes individual's subjective assessment of their own well-being (SWB). Some studies have suggested that diet influences SWB, thus, this work aimed to add novel information on the association of MD and SWB in a sample of Portuguese adults. Data on sociodemographic, economic, lifestyle, diet, and SWB were collected through a self-filled online questionnaire. MD adherence was assessed by the Mediterranean Diet Adherence Screener (MEDAS) score ]. Results showed a moderate adherence to the MD in 490 Portuguese adults (mean MEDAS of 7.4 ± 2.1). A higher MD adherence was found to be significantly positively associated with women, employed individuals, a higher number of meals per day, and those with frequent contact with nature (p-value < 0.0025, using Bonferroni adjustment). As a novelty, this study divided the participants into low SWB, medium SWB, and medium to high SWB profiles (3.9 ± 1.0; 6.2 ± 1.0; 8.2 ± 1.3, respectively; p-value < 0.05), which reported significantly increasing MEDAS scores (6.5 ± 2.1; 7.3 ± 2.1; 7.8 ± 1.9; respectively, p-value < 0.05).

Natural and synthetic 2'-hydroxy-chalcones and aurones: synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity.

A series of 2'-hydroxy-chalcones and their oxidative cyclization products, aurones, have been synthesized and tested for their antioxidant and lipoxygenase inhibitory activity. The natural product aureusidin (31) was synthesized in high yield by a new approach. An extensive structure-relationship study was performed and revealed that several chalcones and aurones possess an appealing pharmacological profile combining high antioxidant and lipid peroxidation activity with potent soybean LOX inhibition.

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability.

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790.

Coumarin derivatives protection against ROS production in cellular models of Abeta toxicities.

The role of oxidative stress and free radicals in the development of Alzheimer's disease (AD) has been the focus of many recent studies. The role of hydrogen peroxide (H(2)O(2)) in AD is thought to be associated with Abeta (amyloid - beta) damage in cells. A number of coumarin derivatives were previously found to be potent anti-inflammatory and antioxidant agents. Herein, these coumarin derivatives were tested as H(2)O(2) scavengers with the DCF assay using two types of neuronal cells: (a) wild type (N2a) neuroblastoma cells and (b) APP/PS1 transgenic cell line expressing Abeta. Their scavenging activity was varied between the types of cell cultures and it was found to be concentration and time dependent in the mutant cells. Their protective role against cell death further supports this notion. These results suggest that these compounds could be used as a template in the design of new molecules with a possible role in AD.

Synthesis and antiinflammatory activity of coumarin derivatives.

The synthesis of several coumarin Mannich bases is described. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity was determined experimentally by RPTLC method. All compounds were evaluated for their antiinflammatory and antioxidant activity and for their ability to inhibit in vitro lipoxygenase. The derivatives were found to present antioxidant and antiinflammatory activities. The tested derivatives inhibited carraggeenin-induced hind paw edema. They also significantly suppressed the arthritis induced by Freund's adjuvant. Compound 10, the most active in vivo, was found to possess protective properties against adjuvant-induced arthritis in rats. The biological in vitro activities were concentration dependent. Hydrophilicity, the presence of a free 7-OH, and steric requirements for the substituent at position 8 are the most important factors in terms of SAR. An attempt was made to correlate several physicochemical properties of the molecules with their in vivo/in vitro activity.

Synthesis and evaluation of the antioxidative potential of minoxidil-polyamine conjugates.

A series of conjugates (MNX-CO-PA) of minoxidil (MNX) with the polyamines (PAs) putrescine (PUT), spermidine (SPD) and spermine (SPM) as well as dopamine were produced through activation of MNX with N,N'-carbonyldiimidazole, followed by reaction with dopamine or selectively protected PAs and acid-mediated deprotection. These conjugates together with conjugates of the general type MNX-PA or PA-MNX-PA, readily produced using literature protocols, were tested as antioxidants. The most potent inhibitors of lipid peroxidation were the conjugates MNX-SPM (2, 94%), SPM-MNX-SPM (4, 94%) and MNX-N(4)-SPD (7, 91%) and MNX (91%). The most powerful lipoxygenase (LOX) inhibitors were MNX (IC50 = 20 µM) and the conjugates MNX-N(8)-SPD (9, IC50 = 22.1 µM), MNX-CO-dopamine (11, IC50 = 28 µM) and MNX-N(1)-SPD (8, IC50 = 30 µM). The most interesting conjugates 2, MNX-CO-PUT (5), 8 and 11 as well as MNX were generally found to exhibit weaker (22-36.5%) or no (conjugate 8) anti-inflammatory activity than indomethacin (47%) with the exception of MNX which showed almost equal potency (49%) to indomethacin. The cytocompatibility of conjugates and MNX at the highest concentration of 100 µM showed a survival percentage of 87-107%, with the exception of conjugates with SPM (compound 2) and MNX-CO-SPM (6), which showed considerable cytotoxicity (survival percentage 8-14%). Molecular docking studies were carried on conjugate 9 and the parent compound MNX and were found to be in accordance with our experimental biological results.

Non-steroidal antiinflammatory drug-copper(II) complexes: structure and biological perspectives.

Copper(II) complexes with the non-steroidal antiinflammatory drug mefenamic acid in the presence of aqua or nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine or pyridine) have been synthesized and characterized. The crystal structures of [(2,2'-bipyridine)bis(mefenamato)copper(II)], 2, [(2,2'-bipyridylamine)bis(mefenamato)copper(II)], 4, and [bis(pyridine)bis(methanol)bis(mefenamato)copper(II)], 5, have been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [bis(aqua)tetrakis(mefenamato)dicopper(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the complexes can bind to CT DNA by the intercalative binding mode verified also by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting strong competition with EB. Mefenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. All the compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity.

One-pot microwave assisted synthesis under green chemistry conditions, antioxidant screening, and cytotoxicity assessments of benzimidazole Schiff bases and pyrimido[1,2-a]benzimidazol-3(4H)-ones.

The synthesis of a number of benzimidazole Schiff bases 3 and 3-oxo-pyrimido[1,2-a]benzimidazoles 4 in excellent yields by a one-step sequence from the reaction of 2-aminobenzimidazole under green chemistry conditions is described. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved based on the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS and elemental analysis data. To the synthesized Schiff bases the E-configuration was assigned on the basis of comparison of experimental and calculated (DFT) (13)C NMR chemical shifts. Compounds 3 and 4 were evaluated as inhibitors of lipoxygenase (LOX) and of lipid peroxidation (LPO). All the tested derivatives showed inhibition of lipid peroxidation, whereas most of them were found to have higher activation than the reference compound trolox; The Schiff bases 3e, 3h, and 3i, and the pyrimidobenzimidazoles 4a, 4e and 4f were found to be the most potent. The most potent LOX inhibitor within the subset of Schiff bases was found compound 3i, followed by 3f, whereas compounds 4a and 4g were found the most potent of the 3-oxo-pyrimido[1,2-a]benzimidazole group. Moreover, some cytotoxicity assessments were undertaken, whereupon it was found that Schiff base 3i and pyrimidobenzimidazoles 4e and 4f did not exhibit cytotoxicity at similar concentrations resembling thus the inhibitory activity of lipid peroxidation. The most cytotoxic Schiff base and pyrimidobenzimidazole were found to be 3d and 4c, respectively.

1,5-Benzoxazepines vs 1,5-benzodiazepines. one-pot microwave-assisted synthesis and evaluation for antioxidant activity and lipid peroxidation inhibition.

Amino-1,5-benzoxazepines 2 and 5 and hydroxyl-1,5-benzodiazepines 3 and 6 have been synthesized in one-pot solvent-free conditions from 2,3-diaminophenol and ketones through microwave assisted acid catalysis, the benzoxazepine/benzodiazepine ratio depending on the R(1) and R(3) aryl substituents. The otherwise inaccessible and unknown 2,2-dimethyl-4-aryl-1,5-benzodiazepines 8 were also prepared in an analogous manner. The reaction mechanism was investigated by means of DFT calculations. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved on the basis of the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS, and elemental analysis data, whereas the presence of an amino group in 5 and of a hydroxyl in 6 was confirmed by derivatization. Compounds 2, 3, 5f, 6a, 6c, 6d, 6f, 6h, 8c, and 12 were evaluated as antioxidants and lipid peroxidation inhibitors in vitro. Compound 6f was also evaluated as anti-inflammatory agent in vivo. Compounds 2 and 6f were found to be the most potent as inhibitors of lipoxygenase and of lipid peroxidation, respectively.

Nitric oxide release from coumarin-7-azomethine derivatives in the presence of thiol.

A series of coumarin derivatives containing a 7-azomethine linkage with anti-inflammatory activity were tested for nitric oxide release in the presence of thiol cofactors in vitro. It was found that nitric oxide release was dependent on the nature of thiol.

Antiinflammatory and antioxidant evaluation of novel coumarin derivatives.

Several coumarin derivatives have been reported to present multiple biological activities and especially antiinflammatory/antioxidant activities. Recently the synthesis and in vivo/in vitro anti-inflammatory/antioxidant activities of several new coumarin derivatives with a 7-azomethine linkage have been reported. In the present study these derivatives were further tested for their antioxidant ability. Some of them were found in vitro to inhibit lipid peroxidation and to strongly scavenge superoxide radicals. Compound 3 was found to potently inhibit cyclooxygenase-1 (COX-1) and the yeast-induced rat paw oedema. The most active compounds within the set were tested against adjuvant-induced arthritis. Compound 3 was found to significantly protect the rats from adjuvant-induced arthritis (when it is administered from the first day or when it is administered the fourteenth day, with the first symptoms of the disease). An attempt was made to delineate the possible mechanism of action of the studied compounds.