Resveratrol and vascular health: evidence from clinical studies and mechanisms of actions related to its metabolites produced by gut microbiota.

Cardiovascular diseases are among the leading causes of mortality worldwide, with dietary factors being the main risk contributors. Diets rich in bioactive compounds, such as (poly)phenols, have been shown to potentially exert positive effects on vascular health. Among them, resveratrol has gained particular attention due to its potential antioxidant and anti-inflammatory action. Nevertheless, the results in humans are conflicting possibly due to interindividual different responses. The gut microbiota, a complex microbial community that inhabits the gastrointestinal tract, has been called out as potentially responsible for modulating the biological activities of phenolic metabolites in humans. The present review aims to summarize the main findings from clinical trials on the effects of resveratrol interventions on endothelial and vascular outcomes and review potential mechanisms interesting the role of gut microbiota on the metabolism of this molecule and its cardioprotective metabolites. The findings from randomized controlled trials show contrasting results on the effects of resveratrol supplementation and vascular biomarkers without dose-dependent effect. In particular, studies in which resveratrol was integrated using food sources, i.e., red wine, reported significant effects although the resveratrol content was, on average, much lower compared to tablet supplementation, while other studies with often extreme resveratrol supplementation resulted in null findings. The results from experimental studies suggest that resveratrol exerts cardioprotective effects through the modulation of various antioxidant, anti-inflammatory, and anti-hypertensive pathways, and microbiota composition. Recent studies on resveratrol-derived metabolites, such as piceatannol, have demonstrated its effects on biomarkers of vascular health. Moreover, resveratrol itself has been shown to improve the gut microbiota composition toward an anti-inflammatory profile. Considering the contrasting findings from clinical studies, future research exploring the bidirectional link between resveratrol metabolism and gut microbiota as well as the mediating effect of gut microbiota in resveratrol effect on cardiovascular health is warranted.

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-ß- 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.

Underrated aspects of a true Mediterranean diet: understanding traditional features for worldwide application of a "Planeterranean" diet.

Over the last decades, the Mediterranean diet gained enormous scientific, social, and commercial attention due to proven positive effects on health and undeniable taste that facilitated a widespread popularity. Researchers have investigated the role of Mediterranean-type dietary patterns on human health all around the world, reporting consistent findings concerning its benefits. However, what does truly define the Mediterranean diet? The myriad of dietary scores synthesizes the nutritional content of a Mediterranean-type diet, but a variety of aspects are generally unexplored when studying the adherence to this dietary pattern. Among dietary factors, the main characteristics of the Mediterranean diet, such as consumption of fruit and vegetables, olive oil, and cereals should be accompanied by other underrated features, such as the following: (i) specific reference to whole-grain consumption; (ii) considering the consumption of legumes, nuts, seeds, herbs and spices often untested when exploring the adherence to the Mediterranean diet; (iii) consumption of eggs and dairy products as common foods consumed in the Mediterranean region (irrespectively of the modern demonization of dietary fat intake). Another main feature of the Mediterranean diet includes (red) wine consumption, but more general patterns of alcohol intake are generally unmeasured, lacking specificity concerning the drinking occasion and intensity (i.e., alcohol drinking during meals). Among other underrated aspects, cooking methods are rather simple and yet extremely varied. Several underrated aspects are related to the quality of food consumed when the Mediterranean diet was first investigated: foods are locally produced, minimally processed, and preserved with more natural methods (i.e., fermentation), strongly connected with the territory with limited and controlled impact on the environment. Dietary habits are also associated with lifestyle behaviors, such as sleeping patterns, and social and cultural values, favoring commensality and frugality. In conclusion, it is rather reductive to consider the Mediterranean diet as just a pattern of food groups to be consumed decontextualized from the social and geographical background of Mediterranean culture. While the methodologies to study the Mediterranean diet have demonstrated to be useful up to date, a more holistic approach should be considered in future studies by considering the aforementioned underrated features and values to be potentially applied globally through the concept of a "Planeterranean" diet.

Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?

Isoflavones are a group of (poly)phenols, also defined as phytoestrogens, with chemical structures comparable with estrogen, that exert weak estrogenic effects. These phytochemical compounds have been targeted for their proven antioxidant and protective effects. Recognizing the increasing prevalence of cardiovascular diseases (CVD), there is a growing interest in understanding the potential cardiovascular benefits associated with these phytochemical compounds. Gut microbiota may play a key role in mediating the effects of isoflavones on vascular and endothelial functions, as it is directly implicated in isoflavones metabolism. The findings from randomized clinical trials indicate that isoflavone supplementation may exert putative effects on vascular biomarkers among healthy individuals, but not among patients affected by cardiometabolic disorders. These results might be explained by the enzymatic transformation to which isoflavones are subjected by the gut microbiota, suggesting that a diverse composition of the microbiota may determine the diverse bioavailability of these compounds. Specifically, the conversion of isoflavones in equol-a microbiota-derived metabolite-seems to differ between individuals. Further studies are needed to clarify the intricate molecular mechanisms behind these contrasting results.

Effect of olive leaf phytochemicals on the anti-acetylcholinesterase, anti-cyclooxygenase-2 and ferric reducing antioxidant capacity.

In this study, the phytochemical profile of fifty olive leaves (OL) extracts from Spain, Italy, Greece, Portugal, and Morocco was characterized and their anti-cholinergic, anti-inflammatory, and antioxidant activities were evaluated. Luteolin-7-O-glucoside, isoharmnentin, and apigenin were involved in the acetylcholinesterase (AChE) inhibitory activity, while oleuropein and hydroxytyrosol showed noteworthy potential. Secoiridoids contributed to the cyclooxygenase-2 inhibitory activity and antioxidant capacity. Compounds such as oleuropein, ligstroside and luteolin-7-O-glucoside, may exert an important role in the ferric reducing antioxidant capacity. It should be also highlighted the role of hydroxytyrosol, hydroxycoumarins, and verbascoside concerning the antioxidant activity. This research provides valuable insights and confirms that specific compounds within OL extracts contribute to distinct anti-cholinergic, anti-inflammatory, and anti-oxidative effects.

Correction: Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Correction for 'Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis' by Alicia Saz-Lara et al., Food Funct., 2024, https://doi.org/10.1039/D3FO05061K.

Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Background: Arterial stiffness and atherosclerosis are known risk factors for cardiovascular morbidity and mortality. Vegetarian diets have been associated with cardiovascular benefits, including improvements in metabolic parameters. However, the impact of a vegetarian diet on cardiovascular parameters, specifically arterial stiffness and atherosclerosis, in healthy individuals remains unclear. Thus, this study aims to analyze differences in arterial stiffness and atherosclerosis between vegetarian and omnivorous diets in healthy subjects. Methods: A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for studies examining the association between vegetarian and omnivorous diets with arterial stiffness and atherosclerosis. Cross-sectional studies reporting carotid to femoral pulse wave velocity (cf-PWv) as a measure of arterial stiffness and carotid intima media thickness (c-IMT) as a measure of atherosclerosis were included. Data were synthesized using random effects models, and sensitivity analyses, meta-regressions, and assessment of publication bias were performed. Results: Ten studies were included in the systematic review, and seven studies were included in the meta-analysis. The pooled analysis demonstrated that individuals following a vegetarian diet had differences in the levels of arterial stiffness (cf-PWv) compared to those following an omnivorous diet (MD: -0.43 m s-1; 95% CI: -0.63, -0.23). Similarly, atherosclerosis (c-IMT) was found to be different in individuals adhering to a vegetarian dietary pattern (MD = -29.86 mm; 95% CI: -58.41, -1.32). Conclusions: Our findings suggest that a vegetarian diet is associated with improved arterial stiffness and reduced atherosclerosis in healthy individuals. These results support the inclusion of a well-balanced vegetarian dietary pattern in the prevention and management of cardiovascular diseases. However, further research is needed to explore the effects of a vegetarian diet on arterial health in diverse populations and to assess long-term cardiovascular outcomes.

Rapid determination of geographical authenticity and pungency intensity of the red Sichuan pepper (Zanthoxylum bungeanum) using differential pulse voltammetry and machine learning algorithms.

The development of an analytical method for assessing pungency intensity and determining geographical origins is crucial for evaluating the quality of visually similar Zanthoxylum bungeanum pericarp (PZB). This study analyzed 210 PZB samples from 14 origins across China, focusing on origin adulteration identification and pungency intensity using a combination of differential pulse voltammetry (DPV) and machine learning algorithms. The artificial neural network (ANN) and K-nearest neighbor (KNN) algorithms provided the highest accuracy in origin identification (100 %) and adulteration detection (97.9 %) respectively. Moreover, the ANN excelled in predicting pungency intensity (R2 = 0.918). Assessment via feature importance analysis of DPV features revealed that segments of polyphenols (0.34-0.52 V and 1.0-1.2 V) and alkylamides (1.0-1.2 V) contributed significantly to the PZB pungency intensity. These findings highlight the potential of DPV as a reliable method for assessing the quality of PZB, and offer a promising solution for ensuring the geographical authenticity of this important crop.

Nutritional Modulation of Hepcidin in the Treatment of Various Anemic States.

Twenty years after its discovery, hepcidin is still considered the main regulator of iron homeostasis in humans. The increase in hepcidin expression drastically blocks the flow of iron, which can come from one's diet, from iron stores, and from erythrophagocytosis. Many anemic conditions are caused by non-physiologic increases in hepcidin. The sequestration of iron in the intestine and in other tissues poses worrying premises in view of discoveries about the mechanisms of ferroptosis. The nutritional treatment of these anemic states cannot ignore the nutritional modulation of hepcidin, in addition to the bioavailability of iron. This work aims to describe and summarize the few findings about the role of hepcidin in anemic diseases and ferroptosis, as well as the modulation of hepcidin levels by diet and nutrients.

Fish Intake in Relation to Fatal and Non-Fatal Cardiovascular Risk: A Systematic Review and Meta-Analysis of Cohort Studies.

Epidemiological studies have shown that eating fish significantly reduces cardiovascular disease (CVD) incidence and mortality. However, more focused meta-analyses based on the most recent results from prospective cohort studies are needed. This systematic review and meta-analysis aims to update the association between fish intake and cardiovascular disease (CVD) risk using recent prospective studies. A systematic review and meta-analysis following the PRISMA guideline was conducted based on a random effects synthesis of multivariable-adjusted relative risks (RRs) of high vs. low categories of fish intake in relation to CVD incidence and mortality. Non-linear meta-regression was applied to investigate the shape of the association between fish intake and CVD risk. Sensitivity analysis and stratifications by type of CVD outcome, type of fish intake and type of cooking were performed. Based on 18 papers reporting 17 independent estimates of CVD risk (1,442,407 participants and 78,805 fatal and non-fatal CVD events), high vs. low intake of fish corresponded to about 8% reduced CVD risk (RR = 0.93 [0.88-0.98]). According to a non-linear dose-response meta-regression, 50 g of fish intake per day corresponded to a statistically significant 9% reduced fatal and non-fatal CVD risk (RR = 0.92 [0.90-0.95]). Similarly, fish intake in the range of a weekly intake of two to three portions of fish with a size of 150 g resulted in 8% fatal and non-fatal CVD risk reduction (RR = 0.93 [0.91-0.96]). The recommended two portions of fish a week reduces the risk of CVD outcomes by approximately 10%. A full portion of fish a day reduces CVD risk by up to 30%.

Saltiness enhancement by "má là" umami flavor in NaCl model aqueous and oil-added systems.

The health concerns associated with high dietary sodium and the quest for a sensory experience have prompted the need for new strategies that can reduce the salt content of foods and have good acceptability. To investigate the cross-modal interaction effects of "má là" umami flavor (total of eight carriers) on the saltiness perception and effective sodium reduction in low-to-strong NaCl aqueous solutions (0.203 %-1.39 %) and oil-added systems (5 %, 10 %, 15 %, 20 %, 25 % canola oil, wt%), sixteen assessors were selected and two methods including saltiness intensity comparison with a category scale and rating with a generalized Labeled Magnitude Scale (gLMS) were used. The results showed PnSnUn carriers significantly enhance saltiness at moderate-to-strong NaCl solutions, and higher saltiness intensity with the addition of canola oil, especially at 25 % oil level. In addition, based on the developed Stevens' power function the sodium reduction was calculated, it was evident that two "má là" umami flavor combinations (one flavor combination was low "má", low "là" and moderate umami, and the other flavor combination with moderate "má", low "là" and moderate umami) were found to perform best with maximum sodium reduction of 18.88 % and 18 %, respectively, and when incorporating 25 % canola oil, the maximum sodium reduction raised by approximately 10 % (to 28.00 % and 28.42 %). This research not only confirmed the positive modulating effect of the "má là" umami flavor on saltiness perception in NaCl solutions, but also showed that the presence of oil further enhanced this effect. This work offered a new and promising insight into the development of foods with reduced sodium content while maintaining the saltiness properties.

Insights into the cellular, molecular, and epigenetic targets of gamma-aminobutyric acid against diabetes: a comprehensive review on its mechanisms.

Diabetes is a metabolic disease due to impaired or defective insulin secretion and is considered one of the most serious chronic diseases worldwide. Gamma-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid commonly present in a wide range of foods. A number of studies documented that GABA has good anti-diabetic potential. This review summarized the available dietary sources of GABA as well as animal and human studies on the anti-diabetic properties of GABA, while also discussing the underlying mechanisms. GABA may modulate diabetes through various pathways such as inhibiting the activities of α-amylase and α-glucosidase, promoting ß-cell proliferation, stimulating insulin secretion from ß-cells, inhibiting glucagon secretion from α-cells, improving insulin resistance and glucose tolerance, and increasing antioxidant and anti-inflammatory activities. However, further mechanistic studies on animals and human are needed to confirm the therapeutic effects of GABA against diabetes.

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-product.

Asparagus saponins: effective natural beneficial ingredient in functional foods, from preparation to applications.

Asparagus species is recognized as a perennial herb with several valuable functional ingredients, and has been widely used as medicine and food since ancient times. Among its main chemical constituents, saponins play a vital role in the health benefits and biological activities including anti-cancer, antioxidant, immunomodulatory, anti-microbial, anti-inflammatory, and hypoglycemic. This review summarizes the preparation methods, structure and classification, biological functions, as well as the food and non-food applications of asparagus saponins, with a special emphasis on its anti-cancer effects in vitro and in vivo. Further, the main challenges and limitations of the current research trends in asparagus saponins are highlighted after a detailed analysis of the recent research information. This review bridges the gap between bioactive components and human health and aids current research on functional and health-promoting foods and medicinal application of Asparagus saponins.

Can the phenolic compounds of Manuka honey chemosensitize colon cancer stem cells? A deep insight into the effect on chemoresistance and self-renewal.

Manuka honey, which is rich in pinocembrin, quercetin, naringenin, salicylic, p-coumaric, ferulic, syringic and 3,4-dihydroxybenzoic acids, has been shown to have pleiotropic effects against colon cancer cells. In this study, potential chemosensitizing effects of Manuka honey against 5-Fluorouracil were investigated in colonspheres enriched with cancer stem cells (CSCs), which are responsible for chemoresistance. Results showed that 5-Fluorouracil increased when it was combined with Manuka honey by downregulating the gene expression of both ATP-binding cassette sub-family G member 2, an efflux pump and thymidylate synthase, the main target of 5-Fluorouracil which regulates the ex novo DNA synthesis. Manuka honey was associated with decreased self-renewal ability by CSCs, regulating expression of several genes in Wnt/ß-catenin, Hedgehog and Notch pathways. This preliminary study opens new areas of research into the effects of natural compounds in combination with pharmaceuticals and, potentially, increase efficacy or reduce adverse effects.

The Application of Digital Technologies and Artificial Intelligence in Healthcare: An Overview on Nutrition Assessment.

In the last decade, artificial intelligence (AI) and AI-mediated technologies have undergone rapid evolution in healthcare and medicine, from apps to computer software able to analyze medical images, robotic surgery and advanced data storage system. The main aim of the present commentary is to briefly describe the evolution of AI and its applications in healthcare, particularly in nutrition and clinical biochemistry. Indeed, AI is revealing itself to be an important tool in clinical nutrition by using telematic means to self-monitor various health metrics, including blood glucose levels, body weight, heart rate, fat percentage, blood pressure, activity tracking and calorie intake trackers. In particular, the application of the most common digital technologies used in the field of nutrition as well as the employment of AI in the management of diabetes and obesity, two of the most common nutrition-related pathologies worldwide, will be presented.

Muscular involvement in long-term type 1 diabetes: Does it represent an underestimated complication?

OBJECTIVES: Structural, metabolic, and functional signs of skeletal muscle damage have been identified in individuals affected by type 1 diabetes (T1D), but, to our knowledge, no guidelines for the diagnosis and treatment of muscle impairment exist and studies on T1D and muscle health remain limited. The aim of this study was to evaluate the prevalence of sarcopenia in a long-term T1D population and to assess the effects of some clinical parameters on muscle mass and function. METHODS: Thirty-nine patients affected by T1D were enrolled. Body mass index (BMI), body composition (appendicular lean mass index [ALMI] and fat mass [FM]), and muscle strength were measured. Additionally, the relationship between Mediterranean diet adherence and sarcopenia was assessed. RESULTS: In the present sample (mean age 49.32 ± 13.49 y, 41.1% women, mean duration of diabetes 30.13 ± 12.28 y), the prevalence of sarcopenia was 7.7% (12.5 % in women and 4.35% in men). The prevalence of low ALMI was 23.1% (25% in women and 21.74% in men). Significant inverse correlations were found between ALMI and duration of diabetes and ALMI and FM; and significant positive correlations between ALMI and BMI, physical activity level, and muscle strength. At the same time, significant inverse correlations were observed between muscle strength and duration of diabetes and muscle strength and FM. CONCLUSIONS: We observed a high prevalence of low muscle mass, similar to those found in the older age groups of the general population (25 years in advance) and our findings suggest a possible pathogenetic role of T1D duration on muscle trophism and function.

The In Vitro Effects of Romina Strawberry Extract on 3D Uterine Leiomyosarcoma Cells.

Leiomyosarcoma is an aggressive soft tissue sarcoma derived from the smooth muscle cells of the uterus. We tested the effect of Romina strawberry extract treatment on three-dimensional cultured uterine leiomyosarcoma cells. We established 3D cultures in agarose gel, where the cells seeded were able to form spheroids. We performed the observation and counting of the spheroids with a phase-contrast optical microscope, finding a decrease in the number of spheroids formed in the plates after 24 and 48 h treatment with 250 µg/mL of cultivar Romina strawberry extract. We also characterized the spheroids morphology by DNA binding fluorescent-stain observation, hematoxylin and eosin stain, and Masson's trichrome stain. Finally, the real-time PCR showed a reduced expression of extracellular matrix genes after strawberry treatment. Overall, our data suggest that the fruit extract of this strawberry cultivar may be a useful therapeutic adjuvant for the management of uterine leiomyosarcoma.

Health benefits of saponins and its mechanisms: perspectives from absorption, metabolism, and interaction with gut.

Saponins, consisting of sapogenins as their aglycones and carbohydrate chains, are widely found in plants and some marine organisms. Due to the complexity of the structure of saponins, involving different types of sapogenins and sugar moieties, investigation of their absorption and metabolism is limited, which further hinders the explanation of their bioactivities. Large molecular weight and complex structures limit the direct absorption of saponins rendering their low bioavailability. As such, their major modes of action may be due to interaction with the gastrointestinal environment, such as enzymes and nutrients, and interaction with the gut microbiota. Many studies have reported the interaction between saponins and gut microbiota, that is, the effects of saponins on changing the composition of gut microbiota, and gut microbiota playing an indispensable role in the biotransformation of saponins into sapogenins. However, the metabolic routes of saponins by gut microbiota and their mutual interactions are still sparse. Thus, this review summarizes the chemistry, absorption, and metabolic pathways of saponins, as well as their interactions with gut microbiota and impacts on gut health, to better understand how saponins exert their health-promoting functions.

Dietary antioxidants and lifespan: Relevance of environmental conditions, diet, and genotype of experimental models.

The rise of life expectancy in current societies is not accompanied, to date, by a similar increase in healthspan, which represents a great socio-economic problem. It has been suggested that aging can be manipulated and then, the onset of all age-associated chronic disorders can be delayed because these pathologies share age as primary underlying risk factor. One of the most extended ideas is that aging is consequence of the accumulation of molecular damage. According to the oxidative damage theory, antioxidants should slow down aging, extending lifespan and healthspan. The present review analyzes studies evaluating the effect of dietary antioxidants on lifespan of different aging models and discusses the evidence on favor of their antioxidant activity as anti-aging mechanisms. Moreover, possible causes for differences between the reported results are evaluated.