The Effect of Dietary Polyphenols on Vascular Health and Hypertension: Current Evidence and Mechanisms of Action

The study was a part of the ABIOCOR (Role of dietary antioxidants and biofortification of vegetable crops for human health) project funded by the "Piano di incentivi per la ricerca di Ateneo 2020/2022" of the University of Catania, Italy (G.G., M.L., F.G.). The figures have been generated by using Servier Medical Art available at smart.servier.com.The aim of this review was to explore existing evidence from studies conducted on humans and summarize the mechanisms of action of dietary polyphenols on vascular health, blood pressure and hypertension. There is evidence that some polyphenol-rich foods, including berry fruits rich in anthocyanins, cocoa and green tea rich in flavan-3-ols, almonds and pistachios rich in hydroxycinnamic acids, and soy products rich in isoflavones, are able to improve blood pressure levels. A variety of mechanisms can elucidate the observed effects. Some limitations of the evidence, including variability of polyphenol content in plant-derived foods and human absorption, difficulty disentangling the effects of polyphenols from other dietary compounds, and discrepancy of doses between animal and human studies should be taken into account. While no single food counteracts hypertension, adopting a plant-based dietary pattern including a variety of polyphenol-rich foods is an advisable practice to improve blood pressure."Piano di incentivi per la ricerca di Ateneo 2020/2022" of the University of Catania, Ital

Relation between Strawberry Fruit Redness and Bioactivity: Deciphering the Role of Anthocyanins as Health Promoting Compounds

The red colour of most berries is often associated to fruit healthiness, since it has been linked to enrichment in anthocyanins (polyphenol with antioxidative properties). However, recent studies suggest that anthocyanins could not be the major contributors to bioactivity leading to uncertainty about their role as important molecules in the generation of health-promoting properties. To shed light on this issue, spectrophotometric and HPLC techniques were used for characterizing the content of phenolic compounds, including anthocyanins, in fruits of red (Fragaria x ananassa, cv. Fortuna) and white strawberry (Fragaria vesca spp. XXVIII) species (distinguishing receptacle from achene). In addition, the effect of these extracts on the reduction of intracellular ROS was tested, as well as on the activity of antioxidant enzymes and the quantification of cell oxidation markers. The results showed that white receptacle extracts (deprived of anthocyanins) were able to protect cells from oxidative damage to a greater extent than red fruits. This could be due per se to their high antioxidant capacity, greater than that shown in red fruits, or to the ability of antioxidants to modulate the activity of antioxidant enzymes, thus questioning the positive effect of anthocyanins on the wholesomeness of strawberry fruits. The results shed light on the relevance of anthocyanins in the prevention of health-associated oxidative damage.AVA2019.034 project, co-financed by the FEDER funds (UE) within the “Programa Operativo de Andalucía 2014–2020”Breeding Value project funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 101000747IFAPA, Junta de AndalucíaJdC-I post-doctoral contract with grant reference IJC2020-043910-I, funded by NextGenerationE

Strawberry tree honey in combination with 5-fluorouracil enhances chemosensitivity in human colon adenocarcinoma cells

The authors would like to thank Prof. Gavino Sanna, Department of Chemistry and Pharmacy (University of Sassari, Italy), for providing STH samples. Tamara Y. Forbes-Hernandez is supported by a "Juan de la Cierva-Formacion" post-doctoral contract.Colorectal cancer remains a challenging health burden worldwide. This study aimed to assess the potentiality of Strawberry tree honey (STH), a polyphenol-enriched food, to increase the effectiveness of 5-Fluorouracil (5-FU) in adenocarcinoma (HCT-116) and metastatic (LoVo) colon cancer cell lines. The combined treatment reduced cell viability and caused oxidative stress, by increasing oxidative biomarkers and decreasing antioxidant defence, in a more potent way compared to 5-FU alone. The expression of endoplasmic reticulum (ATF-6, XBP-1) and MAPK (p-p38 MAPK, p-ERK1/2) markers were also elevated after the combined treatment, enhancing the cell cycle arrest through the modulation of regulatory genes (i.e., cyclins and CDKs). Apoptotic gene (i.e., caspases) expressions were also increased after the combined treatment, while those of proliferation (i.e., EGFR), cell migration, invasion (i.e., matrix metallopeptidase) and epithelial–mesenchymal transition (N-cadherin, β-catenin) were suppressed. Finally, the combined treatment led cell metabolism towards a quiescent stage, by reducing mitochondrial respiration and glycolysis. In conclusion, this work represents an initial step to highlight the possibility to use STH in combination with 5-FU in the treatment of colon cancer, even if further in vitro an in vivo studies are strongly needed to confirm the possible chemo-sensitizing effects of STH."Juan de la Cierva-Formacion" post-doctoral contrac

Exploring the Antioxidant, Neuroprotective, and Anti-Inflammatory Potential of Olive Leaf Extracts from Spain, Portugal, Greece, and Italy

The leaves of the olive tree (Olea europaea L.) are one of the major solid wastes from the olive industry. Globally, the European Union is the largest producer of olive by-products, with Spain, Italy, Greece, and Portugal accounting for almost the entire production. Many questions remain to be solved concerning olive leaves (OL), including those related to possible differences in composition and/or biological activities depending on their geographical origin. In the present work, OL from Spain, Italy, Greece, and Portugal have been characterized according to their phytochemical profile, antioxidant capacity, neuroprotective activity, and anti-inflammatory effects. The Spanish and Italian OL samples presented the highest antioxidant and neuroprotective activities, while the Greek OL showed the lowest. These results were strongly associated with the content of oleoside methyl ester and p-hydroxybenzoic acid for the Spanish and Italian samples, respectively, whereas the content of decarboxymethyl elenolic acid dialdehyde form (hydrated) was negatively associated with the mentioned biological activities of the Greek samples. No country-related effect was observed in the anti-inflammatory activity of OL. Comprehensively, this work could provide a useful tool for manufacturers and R&D departments in making environmentally friendly decisions on how OL can be used to generate nutraceutical products based on the composition and origin of this by-productPRIMA EU programSUSTAINOLIVE grant n 1811PID2019-106778RB-I00, funded by MCIN/AEI/10.13039/501100011033 FEDER “Una Manera de Hacer Europ

In Vitro and In Vivo Insights into a Broccoli Byproduct as a Healthy Ingredient for the Management of Alzheimer’s Disease and Aging through Redox Biology

Broccoli has gained popularity as a highly consumed vegetable due to its nutritional and health properties. This study aimed to evaluate the composition profile and the antioxidant capacity of a hydrophilic extract derived from broccoli byproducts, as well as its influence on redox biology, Alzheimer’s disease markers, and aging in the Caenorhabditis elegans model. The presence of glucosinolate was observed and antioxidant capacity was demonstrated both in vitro and in vivo. The in vitro acetylcholinesterase inhibitory capacity was quantified, and the treatment ameliorated the amyloid-β- and tau-induced proteotoxicity in transgenic strains via SOD-3 and SKN-1, respectively, and HSP-16.2 for both parameters. Furthermore, a preliminary study on aging indicated that the extract effectively reduced reactive oxygen species levels in aged worms and extended their lifespan. Utilizing broccoli byproducts for nutraceutical or functional foods could manage vegetable processing waste, enhancing productivity and sustainability while providing significant health benefits.“Visiting Scholars 2022” Program from the Universidad de GranadaFEDER/Junta de Andalucía-Consejería de Economía y Conocimiento, Grant B-AGR-193-UGR18“Contratos-Puente” funded by the Universidad de GranadaFPU fellow with grant reference FPU2018/ 05301 funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro″JdC-I postdoctoral contract with grant reference IJC2020-043910-I, funded by NextGenerationE

Bioactive Properties of Tagetes erecta Edible Flowers: Polyphenol and Antioxidant Characterization and Therapeutic Activity against Ovarian Tumoral Cells and Caenorhabditis elegans Tauopathy

Tagetes erecta is an edible flower deeply rooted in traditional Mexican culture. It holds a central role in the most popular and iconic Mexican celebration, “the Day of the Dead”. Furthermore, it is currently receiving interest as a potential therapeutic agent, motivated mainly by its polyphenol content. The present study aims to evaluate the biological activity of an extract synthesized from the petals of the edible flower T. erecta. This extract showed significant antioxidant scores measured by the most common in vitro methodologies (FRAP, ABTS, and DPPH), with values of 1475.3 μM trolox/g extr, 1950.3 μM trolox/g extr, and 977.7 μM trolox/g extr, respectively. In addition, up to 36 individual polyphenols were identified by chromatography. Regarding the biomedical aspects of the petal extract, it exhibited antitumoral activity against ovarian carcinoma cells evaluated by the MTS assay, revealing a lower value of IC50 compared to other flower extracts. For example, the extract from T. erecta reported an IC50 value half as low as an extract from Rosa × hybrida and six times lower than another extract from Tulbaghia violacea. This antitumoral effect of T. erecta arises from the induction of the apoptotic process; thus, incubating ovarian carcinoma cells with the petal extract increased the rate of apoptotic cells measured by flow cytometry. Moreover, the extract also demonstrated efficacy as a therapeutic agent against tauopathy, a feature of Alzheimer’s disease (AD) in the Caenorhabditis elegans experimental model. Treating worms with the experimental extract prevented disfunction in several motility parameters such as wavelength and swimming speed. Furthermore, the T. erecta petal extract prevented the release of Reactive Oxygen Species (ROS), which are associated with the progression of AD. Thus, treatment with the extract resulted in an approximate 20% reduction in ROS production. These findings suggest that these petals could serve as a suitable source of polyphenols for biomedical applications.FEDER/Junta de Andalucía-Consejería de Economía y Conocimiento, Grants BAGR-193-UGR18, B-AGR-652-UGR20, and P20_00336Postdoctoral fellowship financed by Junta de Andalucia (ref. POSTDOC_21_028

An Olive-Derived Extract 20% Rich in Hydroxytyrosol Prevents beta-Amyloid Aggregation and Oxidative Stress, Two Features of Alzheimer Disease, via SKN-1/NRF2 and HSP-16.2 in Caenorhabditis elegans

The authors gratefully acknowledge the funding support of FEDER/Junta de AndaluciaConsejeria de Economia y Conocimiento, Grant B-AGR-193-UGR18. Also grant PID2019-106778RBI00, funded by MCIN/AEI/10.13039/501100011033 FEDER "Una manera de hacer Europa".Olive milling produces olive oil and different by-products, all of them very rich in different bioactive compounds like the phenolic alcohol hydroxytyrosol. The aim of the present study was to investigate the effects of an olive fruit extract 20% rich in hydroxytyrosol on the molecular mechanisms associated with Alzheimer disease features like A beta- and tau- induced toxicity, as well as on oxidative stress in Caenorhabditis elegans. Moreover, characterization of the extracts, regarding the profile and content of phenolics, as well as total antioxidant ability, was investigated. The study of lethality, growth, pharyngeal pumping, and longevity in vivo demonstrated the lack of toxicity of the extract. One hundred mu g/mL of extract treatment revealed prevention of oxidative stress and a delay in A beta-induced paralysis related with a lower presence of A beta aggregates. Indeed, the extract showed the ability to avoid a certain degree of proteotoxicity associated with aggregation of the tau protein. According to RNAi tests, SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2 were mechanistically associated in the observed effects.FEDER/Junta de AndaluciaConsejeria de Economia y Conocimiento B-AGR-193-UGR18 PID2019-106778RBI00 MCIN/AEI/10.13039/50110001103

Phenolic Compounds in Honey and Their Associated Health Benefits: A Review

Honey is a natural substance appreciated for its therapeutic abilities since ancient times. Its content in flavonoids and phenolic acids plays a key role on human health, thanks to the high antioxidant and anti-inflammatory properties that they exert. Honey possesses antimicrobial capacity and anticancer activity against different types of tumors, acting on different molecular pathways that are involved on cellular proliferation. In addition, an antidiabetic activity has also been highlighted, with the reduction of glucose, fructosamine, and glycosylated hemoglobin serum concentration. Honey exerts also a protective effect in the cardiovascular system, where it mainly prevents the oxidation of low-density lipoproteins, in the nervous system, in the respiratory system against asthma and bacterial infections, and in the gastrointestinal system. A beneficial effect of honey can also be demonstrated in athletes. The purpose of this review is to summarize and update the current information regarding the role of honey in health and diseases

Effect of Brazil Nuts on Selenium Status, Blood Lipids, and Biomarkers of Oxidative Stress and Inflammation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Conducting of the study and its publication was partially funded from the Jagiellonian University statutory resources (A.M.).Tree nuts, including Brazil nuts, have been hypothesized to impact cardiovascular health through the modulation of oxidative stress and inflammation. Nonetheless, a quantitative analysis of these effects has not been performed. Therefore, the aim of this study was to systematically revise and quantify the effect of Brazil nut intervention on selenium status, blood lipids, and biomarkers of oxidative stress and inflammation using a meta-analytical approach. To meet the goals of this study, a systematic search of PubMed, EMBASE, and Web of Science databases of published randomised clinical trials reporting on dietary interventions with Brazil nuts and their effects on selenium status, blood lipids, and markers of oxidative stress and inflammation was performed. Eight articles were included for systematic review and meta-analysis. Based on the conducted analysis, a significant positive effect of Brazil nuts on selenium blood concentration (SMD = 6.93, 95% CI: 3.99; 9.87) was found. Additionally, a positive effect of Brazil nut intervention on glutathione peroxidase activity (SMD = 0.53, 95% CI: 0.07; 0.99) was observed. However, no significant results were found when considering blood lipid levels, including results for total cholesterol (SMD = -0.22, 95% CI: -0.57; 0.14), HDL cholesterol (SMD = -0.04, 95% CI: -0.28; 0.19) and LDL cholesterol (SMD = -0.15; 95% CI: -0.43; 0.13). In conclusion, the findings from this study suggest that Brazil nut consumption improves selenium status and exerts antioxidant effects, which could be considered a potential pathway for the prevention of metabolic disorders related to altered blood lipid profiles. However, further studies are needed to elucidate the effect of Brazil nuts toward blood lipid profile, also preferably controlling for other biomarkers.Jagiellonian University statutory resource

Alcohol Consumption, Bone Mineral Density, and Risk of Osteoporotic Fractures: A Dose–Response Meta-Analysis

Excess alcohol consumption is known to be detrimental to human health. However, the role of light-to-moderate alcohol intake is under investigation for potential certain health benefits—mostly related to the cardiovascular system. Nevertheless, there is no univocal agreement on this matter, and research is still ongoing to clarify whether there might be other potential outcomes affected by alcohol intake. In this regard, there is evidence that excess alcohol intake may negatively influence the risk of osteoporotic fractures. However, there is no comprehensive evidence of literature assessing the role of alcohol consumption in bone mineral density (BMD) and the risk of osteoporotic fractures. Thus, the aim of this study was to quantitatively assess the dose–response relationship between alcohol intake and BMD and risk of osteoporotic fractures. The Embase and MEDLINE electronic databases were searched from their inception to December 2021 for articles providing a quantifiable measurement of alcohol consumption for at least three categories and (1) a measurement of BMD (and dispersion as continuous variables) in some area of the body or (2) risk of osteoporotic fracture provided as relative risk (RR) or hazard ratio (HR), with a 95% confidence interval (CI) as the measure of the association of each category with alcohol intake. A total of 11 studies including 46,916 individuals with BMD assessment and 8 studies including 240,871 individuals with risk of fracture analysis were included. Compared to non-drinkers, consumption of up to two standard drinks of alcohol per day was correlated with higher lumbar and femur neck BMD values, while up to one standard drink of alcohol was correlated with higher hip BMD compared to no alcohol consumption. Higher risk of hip fractures was found starting from three standard drinks of alcohol per day (RR = 1.33, 95% CI: 1.04; 1.69 for three alcoholic drinks/d, and RR = 1.59, 95% CI: 1.23; 2.05 for four alcoholic drinks/d) compared to no alcohol consumption, with no evidence of heterogeneity. Concerning the risk of any osteoporotic fractures, the risk steadily increased with higher intake of alcohol, although never reaching statistical significance. In conclusion, there is consistent evidence that increased alcohol consumption is associated with higher risk of osteoporotic hip fracture; however, the role of alcohol at lower doses is uncertain, as BMD was even higher in light drinkers compared to abstainers