Natural and Synthetic Flavylium-Based Dyes: The Chemistry Behind the Color.

Flavylium compounds are a well-known family of pigments because they are prevalent in the plant kingdom, contributing to colors over a wide range from shades of yellow-red to blue in fruits, flowers, leaves, and other plant parts. Flavylium compounds include a large variety of natural compound classes, namely, anthocyanins, 3-deoxyanthocyanidins, auronidins, and their respective aglycones as well as anthocyanin-derived pigments (e.g., pyranoanthocyanins, anthocyanin-flavan-3-ol dimers). During the past few decades, there has been increasing interest among chemists in synthesizing different flavylium compounds that mimic natural structures but with different substitution patterns that present a variety of spectroscopic characteristics in view of their applications in different industrial fields. This Review provides an overview of the chemistry of flavylium-based compounds, in particular, the synthetic and enzymatic approaches and mechanisms reported in the literature for obtaining different classes of pigments, their physical-chemical properties in relation to their pH-dependent equilibria network, and their chemical and enzymatic degradation. The development of flavylium-based systems is also described throughout this Review for emergent applications to explore some of the physical-chemical properties of the multistate of species generated by these compounds.

Chitosan/Polyvinyl Alcohol-Based Biofilms Using Ternary Deep Eutectic Solvents towards Innovative Color-Stabilizing Systems for Anthocyanins.

Anthocyanins are amazing plant-derived colorants with highly valuable properties; however, their chemical and color instability issues limit their wide application in different food industry-related products such as active and intelligent packaging. In a previous study, it was demonstrated that anthocyanins could be stabilized into green plasticizers namely deep eutectic solvents (DESs). In this work, the fabrication of edible films by integrating anthocyanins along with DESs into biocompatible chitosan (CHT)-based formulations enriched with polyvinyl alcohol (PVA) and PVA nanoparticles was investigated. CHT/PVA-DES films' physical properties were characterized by scanning electron microscopy, water vapor permeability, swelling index, moisture sorption isotherm, and thermogravimetry analysis. Innovative red-to-blue formulation films were achieved for CHT/PVA nanoparticles (for 5 min of sonication) at a molar ratio 1:1, and with 10% of ternary DES (TDES)-containing malvidin-3-glucoside (0.1%) where the physical properties of films were enhanced. After immersion in solutions at different pH values, films submitted to pHs 5-8 were revealed to be more color stable and resistant with time than at acidic pH values.

Exploring the Potential of Vine Shoots as a Source of Valuable Extracts and Stable Lignin Nanoparticles for Multiple Applications.

Large amounts of vine shoots are generated every year during vine pruning. This residue still presents many of the compounds found in the original plant, including low molecular weight phenolic compounds and structural compounds such as cellulose, hemicellulose, and lignin. For wine-producing regions, the challenge is to develop alternatives that will increase the value of this residue. This work proposes the full valorization of vine shoots, focusing on the extraction of lignin by mild acidolysis for the preparation of nanoparticles. The effect of the pretreatment solvents (ethanol/toluene, E/T, and water/ethanol, W/E), on the chemical and structural features of lignin, was evaluated. The chemical analysis suggests similar composition and structure regardless of the pretreatment solvent, although lignin isolated after pretreatment of biomass with E/T showed a higher content of proanthocyanidins (11%) compared with W/E (5%). Lignin nanoparticles (LNPs) presented an average size ranging from 130-200 nm and showed good stability for 30 days. Lignin and LNPs showed excellent antioxidant properties (half maximal inhibitory concentration, IC50 0.016-0.031 mg/mL) when compared to commercial antioxidants. In addition, extracts resulting from biomass pretreatment showed antioxidant activity, with W/E presenting a lower IC50 (0.170 mg/mL) than E/T (0.270 mg/mL), correlated with the higher polyphenol content of W/E, with (+)-catechin and (-)-epicatechin being the main compounds detected. Overall, this work shows that the pre-treatment of vine shoots with green solvents can yield (i) the production of high-purity lignin samples with antioxidant properties and (ii) phenolic-rich extracts, promoting the integral reuse of this byproduct and contributing to sustainability.

Interactions between Beer Compounds and Human Salivary Proteins: Insights toward Astringency and Bitterness Perception.

Beer is one of the most consumed beverages worldwide with unique organoleptic properties. Bitterness and astringency are well-known key features and, when perceived with high intensity, could lead to beer rejection. Most studies on beer astringency and bitterness use sensory assays and fail to study the molecular events that occur inside the oral cavity responsible for those perceptions. This work focused on deepening this knowledge based on the interaction of salivary proteins (SP) and beer phenolic compounds (PCs) and their effect toward these two sensory attributes. The astringency and bitterness of four different beers were assessed by a sensory panel and were coupled to the study of the SP changes and PC profile characterization of beers. The human SP content was measured before (basal) and after each beer intake using HPLC analysis. The beers' PC content and profile were determined using Folin-Ciocalteu and LC-MS spectrometry, respectively. The results revealed a positive correlation between PCs and astringency and bitterness and a negative correlation between SP changes and these taste modalities. Overall, the results revealed that beers with higher PC content (AAL and IPA) are more astringent and bitter than beers with a lower PC content (HL and SBO). The correlation results suggested that an increase in whole SP content, under stimulation, should decrease astringency and bitterness perception. No correlation was found between the changes in specific families of SP and astringency and bitterness perception.

Functionalization of 7-Hydroxy-pyranoflavylium: Synthesis of New Dyes with Extended Chromatic Stability.

This work reports the functionalization of pyranoflavyliums pigment using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride coupling chemistry. Four cinnamic acids were used to establish an ester bond with the hydroxyl group of the pyranoflavylium, namely 4-dimethylamino-, 4-amino-, 4-bromo-, and trans-cinnamic acids. The experimental condition, namely the molar ratios, solvent, and reaction time, were adjusted to obtain higher reaction yields in a reduced period. Excellent reaction yields of 68%, 85%, 94%, and 99% were achieved for 4-amino, trans-, 4-bromo, and 4-dimethylamino pyranoflavylium cinnamates, respectively. The structure of the functionalized pigments was fully clarified using one-dimensional (1H) and two-dimensional (COSY, HSQC, and HMBC) NMR experiments and HRSM analysis. Regardless of the type of functionalization, the UV-Visible spectrum showed a bathochromic shift (red region) on the maximum absorption wavelength and the absence of acid-base reactions throughout a broad pH range in comparison to the pyranoflavylium precursor. This work offers a valuable environmentally friendly, quick, and straightforward alternative to flavylium compounds' challenging and labor-intensive functionalization, resulting in novel dyes with higher stability and dissimilar chromatic features.

Upcycling Rocha do Oeste Pear Pomace as a Sustainable Food Ingredient: Composition, Rheological Behavior and Microstructure Alone and Combined with Yeast Protein Extract.

This work explores the potential of Rocha do Oeste pear pomace to be used as a sustainable and healthy food ingredient. Moreover, the enrichment with yeast protein extract (YPE) may be useful to design innovative food products. The main goals of this study were to assess pear pomace concerning: (i) chemical composition and antioxidant capacity; (ii) rheology, texture, and microstructure characterization (alone or enriched with YPE), before and after heating. The results showed that pear pomace was a rich source of dietary fibers (74.5% DW), with phenolic compounds (3.9 mg chlorogenic acid equivalents/g dry weight), also presenting antiradical activity (3.90 µmol Trolox equivalents/g DW). Pear pomace showed a shear thinning behavior and a typical soft-gel behavior, which was not affected by YPE enrichment, thus suggesting that YPE did not affect pear pomace technological properties. Thermal treatment also did not alter pear pomace rheological properties. YPE addition induced a decrease in the apparent viscosity and a destabilizing effect, compared to the samples that were subjected to thermal processing. These results highlight the importance of pear pomace and the use of YPE for protein enrichment, opening new opportunities for their exploitation.

Dietary polyglycosylated anthocyanins, the smart option? A comprehensive review on their health benefits and technological applications.

Over the years, anthocyanins have emerged as one of the most enthralling groups of natural phenolic compounds and more than 700 distinct structures have already been identified, illustrating the exceptional variety spread in nature. The interest raised around anthocyanins goes way beyond their visually appealing colors and their acknowledged structural and biological properties have fueled intensive research toward their application in different contexts. However, the high susceptibility of monoglycosylated anthocyanins to degradation under certain external conditions might compromise their application. In that regard, polyglycosylated anthocyanins (PGA) might offer an alternative to overcome this issue, owing to their peculiar structure and consequent less predisposition to degradation. The most recent scientific and technological findings concerning PGA and their food sources are thoroughly described and discussed in this comprehensive review. Different issues, including their physical-chemical characteristics, consumption, bioavailability, and biological relevance in the context of different pathologies, are covered in detail, along with the most relevant prospective technological applications. Due to their complex structure and acyl groups, most of the PGA exhibit an overall higher stability than the monoglycosylated ones. Their versatility allows them to act in a wide range of pathologies, either by acting directly in molecular pathways or by modulating the disease environment attributing an added value to their food sources. Their recent usage for technological applications has also been particularly successful in different industry fields including food and smart packaging or in solar energy production systems. Altogether, this review aims to put into perspective the current state and future research on PGA and their food sources.

Physiological Responses and Technical-Tactical Performance of Youth Basketball Players: A Brief Comparison between 3x3 and 5x5 Basketball.

This study aims to examine youth players' physiological responses and technical-tactical performance when playing simulated 3x3 and 5x5 basketball games. Fifteen well-trained male basketball players (16.6 ± 0.2 years old) participated in scrimmage basketball games under two different conditions: 3x3 (half-court) and 5x5 (full-court). The players' heart rate, muscle oxygen saturation and total hemoglobin data were collected and computed to describe physiological responses, while video analysis was used to characterize their technical-tactical performance. A Bayesian one-way analysis of variance (ANOVA) was used to quantify the predictive influence of both game conditions on the physiological and the technical-tactical variables. The results indicated that different game conditions influenced the players' physiological responses slightly, as only hemoglobin sample entropy increased between the 3x3 and 5x5 game scenarios. Conversely, statistical differences in most of the technical-tactical variables were moderate and decisive in favour of the game condition model. Overall, this study emphasizes that playing 3x3 and 5x5 basketball games lead to relatively negligible differences in the players' physiological response but pronounced variations in their technical-tactical performance. Therefore, important implications may be drawn to the applied field as the specificity of technical-tactical adaptations when playing 3x3 or 5x5 formats should be considered by basketball coaches to better design the training sessions for players that fall within our sample age category.

Interactions of dietary polyphenols with epithelial lipids: advances from membrane and cell models in the study of polyphenol absorption, transport and delivery to the epithelium.

Currently, diet-related diseases such as diabetes, obesity, hypertension, and cardiovascular diseases account for 70% of all global deaths. To counteract the rising prevalence of non-communicable diseases governments are investing in persuasive educational campaigns toward the ingestion of fresh fruits and vegetables. The intake of dietary polyphenols abundant in Mediterranean and Nordic-type diets holds great potential as nutritional strategies in the management of diet-related diseases. However, the successful implementation of healthy nutritional strategies relies on a pleasant sensory perception in the mouth able to persuade consumers to adopt polyphenol-rich diets and on a deeper understanding on the chemical modifications, that affect not only their chemical properties but also their physical interaction with epithelial lipids and in turn their permeability, location within the lipid bilayer, toxicity and biological activity, and fate during absorption at the gastro-intestinal epithelium, transport in circulation and delivery to the endothelium. In this paper, we review the current knowledge on the interactions between polyphenols and their metabolites with membrane lipids in artificial membranes and epithelial cell models (oral, stomach, gut and endothelium) and the findings from polyphenol-lipid interactions to physiological processes such as oral taste perception, gastrointestinal absorption and endothelial health. Finally, we discuss the limitations and challenges associated with the current experimental approaches in membrane and cell model studies and the potential of polyphenol-rich diets in the quest for personalized nutritional strategies ("personalized nutrition") to assist in the prevention, treatment, and management of non-communicable diseases in an increasingly aged population.

A pH-responsive fluorescent sensor based on a new pyranoxanthylium salt.

Stimuli-responsive pigments are very interesting for several technological applications, such as food and cosmetic colorants, color-based sensors and fluorescence probes, among others. In this work, the synthesis of a new xanthylium-derived pigment was developed and the chemical and photophysical properties in hydroalcoholic solution at different pH values were investigated by UV-Vis and fluorescence spectroscopy. The UV-Vis titration of 3,6,8-trihydroxy-11-methylpyranoxanthylium has shown four different colored chemical species (AH+, A, A- and A2-) in hydroalcoholic solution in a pH range between 1 and 12 with the thermodynamic acidic constants of pKa1 = 4.80 ± 0.03, pKa2 = 6.51 ± 0.05 and pKa3 = 8.64 ± 0.01. Regarding fluorescence properties, this dye revealed an interesting pH-dependent emission behavior. In fact, the anionic quinoidal base A- predominant at pH range between 5 and 9 should be mainly responsible for the pronounced fluorescence intensity observed at λex 467 nm/λem 510 nm pair (maximum at pH 7.5). This set of new insights make this dye useful as a potential "off-on-off" pH-responsive fluorescent probe for biological applications. A pyranoxanthylium dye was developed and revealed a selective fluorescence emission between 5 < pH < 9, being maximum at pH 7.5, which make it very interesting as a pH-responsive "off-on-off" fluorescent probe for biomedical applications.

Impact of Phlorotannin Extracts from Fucus vesiculosus on Human Gut Microbiota.

Recent studies indicate that plant polyphenols could be pointed as potential prebiotic candidates since they may interact with the gut microbiota, stimulating its growth and the production of metabolites. However, little is known about the fate of brown seaweeds' phlorotannins during their passage throughout the gastrointestinal tract. This work aimed to evaluate the stability and bioaccessibility of Fucus vesiculosus phlorotannins after being submitted to a simulated digestive process, as well as their possible modulatory effects on gut microbiota and short-chain fatty acids production following a fermentation procedure using fecal inoculates to mimic the conditions of the large intestine. The stability of phlorotannins throughout the gastrointestinal tract was reduced, with a bioaccessibility index between 2 and 14%. Moreover, slight alterations in the growth of certain commensal bacteria were noticed, with Enterococcus spp. being the most enhanced group. Likewise, F. vesiculosus phlorotannins displayed striking capacity to enhance the levels of propionate and butyrate, which are two important short-chain fatty acids known for their role in intestinal homeostasis. In summary, this work provides valuable information regarding the behavior of F. vesiculosus phlorotannins along the gastrointestinal tract, presenting clear evidence that these compounds can positively contribute to the maintenance of a healthy gastrointestinal condition.

The Role of Anthocyanins, Deoxyanthocyanins and Pyranoanthocyanins on the Modulation of Tyrosinase Activity: An In Vitro and In Silico Approach.

Tyrosinase is the central enzyme involved in the highly complex process of melanin formation, catalyzing the rate-limiting steps of this biosynthetic pathway. Due to such a preponderant role, it has become a major target in the treatment of undesired skin pigmentation conditions and also in the prevention of enzymatic food browning. Numerous phenolic-based structures from natural sources have been pointed out as potential tyrosinase inhibitors, including anthocyanins. The aim of the present study was to individually assess the tyrosinase inhibitory activity of eight purified compounds with a variable degree of structural complexity: native anthocyanins, deoxyanthocyanins, and pyranoanthocyanins. The latter two, the groups of anthocyanin-related compounds with enhanced stability, were tested for the first time. Compounds 1 to 4 (luteolinidin, deoxymalvidin, cyanidin-, and malvidin-3-O-glucoside) revealed to be the most effective inhibitors, and further kinetic studies suggested their inhibition mechanism to be of a competitive nature. Structure-activity relationships were proposed based on molecular docking studies conducted with mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (hTYRP1) crystal structures, providing information about the binding affinity and the different types of interactions established with the enzyme's active center which corroborated the findings of the inhibition and kinetic studies. Overall, these results support the applicability of these compounds as pigmentation modulators.

Antitumor Activity of Fucus vesiculosus-Derived Phlorotannins through Activation of Apoptotic Signals in Gastric and Colorectal Tumor Cell Lines.

Seaweeds are one of the largest producers of biomass in the marine environment and a source of multiple bioactive metabolites with valuable health benefits. Among these, phlorotannins have been widely recognized for their promising bioactive properties. The potential antitumor capacity of Fucus vesiculosus-derived phlorotannins remains, however, poorly explored, especially in gastrointestinal tract-related tumors. Therefore, this work aimed to evaluate the cytotoxic properties and possible mechanisms by which F. vesiculosus crude extract (CRD), phlorotannin-rich extract (EtOAc), and further phlorotannin-purified fractions (F1-F9) trigger cell death on different tumor cell lines of the gastrointestinal tract, using flow cytometry. The results indicate that F. vesiculosus samples exert specific cytotoxicity against tumor cell lines without affecting the viability of normal cells. Moreover, it was found that, among the nine different phlorotannin fractions tested, F5 was the most active against both Caco-2 colorectal and MKN-28 gastric cancer cells, inducing death via activation of both apoptosis and necrosis. The UHPLC-MS analysis of this fraction revealed, among others, the presence of a compound tentatively identified as eckstolonol and another as fucofurodiphlorethol, which could be mainly responsible for the promising cytotoxic effects observed in this sample. Overall, the results herein reported contribute to a better understanding of the mechanisms behind the antitumor properties of F. vesiculosus phlorotannin-rich extracts.

Metabolomics Insights of the Immunomodulatory Activities of Phlorizin and Phloretin on Human THP-1 Macrophages.

Dihydrochalcones, phlorizin (PZ) and its aglycone phloretin (PT), have evidenced immunomodulatory effects through several mechanisms. However, the differential metabolic signatures that lead to these properties are largely unknown. Since macrophages play an important role in the immune response, our study aimed to characterise human THP-1 macrophages under PZ and PT exposure. A multiplatform-based untargeted metabolomics approach was used to reveal metabolites associated with the anti-inflammatory mechanisms triggered by the dihydrochalcones in LPS-stimulated macrophages, for the first time. Results showed differential phenotypic response in macrophages for all treatments. Dihydrochalcone treatment in LPS-stimulated macrophages mimics the response under normal conditions, suggesting inhibition of LPS response. Antagonistic effects of dihydrochalcones against LPS was mainly observed in glycerophospholipid and sphingolipid metabolism besides promoting amino acid biosynthesis. Moreover, PT showed greater metabolic activity than PZ. Overall, the findings of this study yielded knowledge about the mechanisms of action PZ and PT at metabolic level in modulating inflammatory response in human cells.

Exploring the Applications of the Photoprotective Properties of Anthocyanins in Biological Systems.

Due to their physical and chemical characteristics, anthocyanins are amongst the most versatile groups of natural compounds. Such unique signature makes these compounds a focus in several different areas of research. Anthocyanins have well been reported as bioactive compounds in a myriad of health disorders such as cardiovascular diseases, cancer, and obesity, among others, due to their anti-inflammatory, antioxidant, anti-diabetic, anti-bacterial, and anti-proliferative capacities. Such a vast number of action mechanisms may be also due to the number of structurally different anthocyanins plus their related derivatives. In this review, we highlight the recent advances on the potential use of anthocyanins in biological systems with particular focus on their photoprotective properties. Topics such as skin aging and eye degenerative diseases, highly influenced by light, and the action of anthocyanins against such damages will be discussed. Photodynamic Therapy and the potential role of anthocyanins as novel photosensitizers will be also a central theme of this review.

Phlorotannins from Fucus vesiculosus: Modulation of Inflammatory Response by Blocking NF-κB Signaling Pathway.

Due to their large spectrum of bioactive properties, much attention has recently been drawn to phlorotannins-i.e., phenolic compounds characteristic from brown macroalgae. This study aimed to evaluate the antioxidant and anti-inflammatory properties of F. vesiculosus phlorotannin extracts and purified fractions. Overall, the crude extract and its ethyl acetate fraction (EtOAc) showed good radical scavenging activity, particularly towards nitric oxide (NO•). Subsequent subfractions of EtOAc (F1 to F9) with different molecular weights were then shown to inhibit lipopolysaccharide-induced NO• production in macrophages, with stronger effects being observed for fractions of lower MWs. Of the three intracellular markers analyzed, inducible NO• synthase showed the highest sensitivity to almost all the phlorotannin-rich samples, followed by interleukin 1ß and cyclooxygenase 2, which was only inhibited by F2. Furthermore, this subfraction inhibited the phosphorylation and degradation of inhibitory protein κBα, thus preventing the activation of NF-κB and blocking the inflammatory cascade at the transcriptional level. This sample was characterized by the presence of a major compound with a deprotonated molecular ion at m/z 507 with a fragmentation pattern coherent with that of a phlorotannin derivative. Overall, this work unveiled some of the mechanistic aspects behind the anti-inflammatory capacity of phlorotannins from F. vesiculosus, endorsing its use as a possible natural source of anti-inflammatory compounds.

Bioactive Peptides and Dietary Polyphenols: Two Sides of the Same Coin.

The call for health-promoting nutraceuticals and functional foods containing bioactive compounds is growing. Among the great diversity of functional phytochemicals, polyphenols and, more recently, bioactive peptides have stood out as functional compounds. The amount of an ingested nutrient able to reach the bloodstream and exert the biological activity is a critical factor, and is affected by several factors, such as food components and food processing. This can lead to unclaimed interactions and/or reactions between bioactive compounds, which is particularly important for these bioactive compounds, since some polyphenols are widely known for their ability to interact and/or precipitate proteins/peptides. This review focuses on this important topic, addressing how these interactions could affect molecules digestion, absorption, metabolism and (biological)function. At the end, it is evidenced that further research is needed to understand the true effect of polyphenol-bioactive peptide interactions on overall health outcomes.

Characterization of Anthocyanins and Anthocyanin-Derivatives in Red Wines during Ageing in Custom Oxygenation Oak Wood Barrels.

The ageing of wines in oak barrels is a key stage in the production of high-quality red wines, with the type of oak chosen and the amount of oxygen received by the wine being the determining factors of the process. This work analyses the effect of ageing the same red wine in barrels with different oxygenation rates for one year (OTR), specifically the effect on the evolution of anthocyanins, their derivatives and the appearance of new pigments according to the oxygen dosage in barrels. Results show that wines aged in High-Wood-OTR barrels have a large quantity of monomeric anthocyanins and wine aged in Low-Wood-OTR barrels presents a major intensity of colour. Moreover, using LC-MS analysis, it was possible to detect and identify different families of anthocyanin derivatives, including the tentative identification of two new aldehyde-flavanol-methylpyranoanthocyanin pigments.

Anthocyanins as Antidiabetic Agents-In Vitro and In Silico Approaches of Preventive and Therapeutic Effects.

Many efforts have been made in the past two decades into the search for novel natural and less-toxic anti-diabetic agents. Some clinical trials have assigned this ability to anthocyanins, although different factors like the food source, the amount ingested, the matrix effect and the time of consumption (before or after a meal) seem to result in contradictory conclusions. The possible mechanisms involved in these preventive or therapeutic effects will be discussed-giving emphasis to the latest in vitro and in silico approaches. Therapeutic strategies to counteract metabolic alterations related to hyperglycemia and Type 2 Diabetes Mellitus (T2DM) may include: (a) Inhibition of carbohydrate-metabolizing enzymes; (b) reduction of glucose transporters expression or activity; (c) inhibition of glycogenolysis and (d) modulation of gut microbiota by anthocyanin breakdown products. These strategies may be achieved through administration of individual anthocyanins or by functional foods containing complexes of anthocyanin:carbohydrate:protein.

Tannins in Food: Insights into the Molecular Perception of Astringency and Bitter Taste.

Astringency and bitterness are organoleptic properties widely linked to tannin compounds. Due to their significance to food chemistry, the food industry, and to human nutrition and health, these tannins' taste properties have been a line of worldwide research. In recent years, significant advances have been made in understanding the molecular perception of astringency pointing to the contribution of different oral key players. Regarding bitterness, several polyphenols have been identified has new agonists of these receptors. This review summarizes the last data about the knowledge of these taste properties perceived by tannins. Ultimately, tannins' astringency and bitterness are hand-in-hand taste properties, and future studies should be adapted to understand how the proper perception of one taste could affect the perception of the other one.