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.

Amyloid Fibrils Produced by Streptococcus sanguinis Contribute to Biofilm Formation and Immune Evasion.

Bacterial surface proteins assembled into amyloids contribute to biofilm formation and host immune evasion. Streptococcus sanguinis, a pioneer colonizer of teeth commonly involved in cardiovascular infections, expresses about thirty-three proteins anchored to the cell wall by sortase A. Here, we characterized the production of amyloid in S. sanguinis strains differing in biofilm and immune evasion phenotypes and investigated the role of sortase A in amyloidogenesis. Amyloid was identified in biofilms formed by nine strains, using Congo red (CR) staining and cross-polarized light microscopy. Additionally, EGCG, an amyloid inhibitor, impaired biofilm maturation in a strain-specific fashion. The amounts of amyloid-like components quantified in culture fluids of nine strains using thioflavin T and fluorimetry negatively correlated with bacterial binding to complement-activating proteins (SAP, C1q), C3b deposition and rates of opsonophagocytosis in PMNs, implying amyloid production in immune evasion. The deletion of the sortase A gene (srtA) in strain SK36 compromised amyloid production and sucrose-independent biofilm maturation. The srtA mutant further showed increased susceptibility to C3b deposition and altered interactions with PMNs as well as reduced persistence in human blood. These findings highlight the contribution of amyloids to biofilm formation and host immune evasion in S. sanguinis strains, further indicating the participation of sortase A substrates in amyloidogenesis.

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.

Corema album Leaves Mediate DNA Damage in Triple-Negative Breast Cancer Cells.

Corema (C.) album is a shrub endemic to the Atlantic coast and has been described as yielding beneficial effects for human health. Nevertheless, studies concerning the bioactivity of C. album leaves are scarce. This study aims at investigating the anticancer potential and mode of action, of an hydroethanolic extract of C. album leaves (ECAL) on triple-negative breast cancer. This is a poor survival breast cancer subtype, owing to its high risk of distant reappearance, metastasis rates and the probability of relapse. The ECAL ability to prevent tumor progression through (i) the inhibition of cell proliferation (cell viability); (ii) the induction of apoptosis (morphological changes, TUNEL assay, caspase-3 cleaved) and (iii) the induction of DNA damage (PARP1 and γH2AX) with (iv) the involvement of NF-κB and of ERK1/2 pathways (AlphaScreen assay) was evaluated. ECAL activated the apoptotic pathway (through caspase-3) along with the inhibition of ERK and NF-κB pathways causing DNA damage and cell death. The large polyphenolic content of ECAL was presumed to be accountable for these effects. The extract of C. album leaves can target multiple pathways and, thus, can block more than one possible means of disease progression, evidencing the anticancer therapeutic potential from a plant source.

Modulating the thermodynamics, kinetics and photochemistry of 7-diethylamino-4'-dimethylaminoflavylium in water/ethanol, SDS and CTAB micelles.

The thermodynamics and kinetics of compound 7-diethylamino-4'-dimethylaminoflavylium were studied in water : ethanol (1 : 1) and water in the presence of SDS and CTAB micelles. The blue flavylium cation is in equilibrium with the pink protonated flavylium cation defined by pKAH2+/AH+ and the yellow trans-chalcone, defined by pKAH+/Ct. The difference between these two pKs gives the pH domain of the flavylium cation, ΔpK = 1.95 in CTAB, ΔpK = 5.6 in water/ethanol (1 : 1) and ΔpK = 8.5 in SDS micelles. On the other hand, the pH domain of the trans-chalcone is limited by pKAH+/Ct and pKCt/Ct-. It is lower in SDS micelles ΔpK = 2.7, increases in ethanol/water (1 : 1) ΔpK = 5.1 and is maximum in CTAB micelles, ΔpK = 6.8. All these effects can be explained by the electric charge present at the micellar surface. Relative energy level diagrams that allow for the explanation of the driving forces for any pH stimuli or light absorption were constructed from the calculated equilibrium constants. Irradiation of the trans-chalcone at 466 nm leads to the formation of the flavylium cation. In water : ethanol (1 : 1), the photochemistry is residual with Φ < 0.00002, while in SDS micelles at pH = 7 light increases the rate of the spontaneous conversion of trans-chalcone to the flavylium cation, with quantum yield Φ = 0.002; photochromism from trans-chalcone to give the flavylium cation with the same quantum yield is also observed in CTAB micelles.

Effects of light-emitting diode therapy on cardiovascular and salivary nitrite responses in postmenopausal women submitted to a single bout of high-intensity interval training.

The aim of the present study was to analyze the effects of light-emitting diode therapy (LEDT) on cardiovascular effort during a single bout of high-intensity interval training (HIIT) and on blood pressure (BP), salivary nitrite, and heart rate variability (HRV) responses after the exercise session in postmenopausal women. Sixteen postmenopausal women between 50 and 70 years of age participated in the present study. The intervention comprised two sessions: placebo plus HIIT and LEDT plus HIIT, with a 14-day interval between sessions. The oxygen uptake (VO2), heart rate (HR), and rating of perceived exertion (RPE) were monitored throughout the HIIT sessions. Salivary samples were taken before, immediately post, and 30' and 60' post-HIIT sessions for nitric oxide (NO) analysis. In addition, HR and BP were checked before, 15 min, 30 min, 45 min, and 60 min post-HIIT sessions. HR data were used to calculate the HRV indices. Cardiovascular parameters during HIIT and BP, HRV, and NO responses were not different between placebo and LEDT conditions (p > 0.05). BP responses increased after compared to pre-exercise (p < 0.01). HRV was impaired post- compared to pre-exercise (p < 0.05). LEDT did not improve physiological performance during HIIT and did not accelerate the recovery of BP and autonomic modulation or change the NO release after exercise in postmenopausal women.

Velocity Prediction of a Pipeline Inspection Gauge (PIG) with Machine Learning.

A device known as a pipeline inspection gauge (PIG) runs through oil and gas pipelines which performs various maintenance operations in the oil and gas industry. The PIG velocity, which plays a role in the efficiency of these operations, is usually determined indirectly from odometers installed in it. Although this is a relatively simple technique, the loss of contact between the odometer wheel and the pipeline results in measurement errors. To help reduce these errors, this investigation employed neural networks to estimate the speed of a prototype PIG, using the pressure difference that acts on the device inside the pipeline and its acceleration instead of using odometers. Static networks (e.g., multilayer perceptron) and recurrent networks (e.g., long short-term memory) were built, and in addition, a prototype PIG was developed with an embedded system based on Raspberry Pi 3 to collect speed, acceleration and pressure data for the model training. The implementation of the supervised neural networks used the Python library TensorFlow package. To train and evaluate the models, we used the PIG testing pipeline facilities available at the Petroleum Evaluation and Measurement Laboratory of the Federal University of Rio Grande do Norte (LAMP/UFRN). The results showed that the models were able to learn the relationship among the differential pressure, acceleration and speed of the PIG. The proposed approach can complement odometer-based systems, increasing the reliability of speed measurements.

Attenuation of Autism-like Behaviors by an Anthocyanin-Rich Extract from Portuguese Blueberries via Microbiota-Gut-Brain Axis Modulation in a Valproic Acid Mouse Model.

Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental pathologies whose current treatment is neither curative nor effective. Anthocyanins are naturally occurring compounds abundant in blueberries and in other red fruits which have been shown to be successful in the treatment of several neurological diseases, at least in in vitro and in vivo disease models. The aim of the present work was to study the ability of an anthocyanin-rich extract (ARE) obtained from Portuguese blueberries to alleviate autism-like symptoms in a valproic acid (VPA) mouse model of ASD and to get insights into the underlying molecular mechanisms of such benefits. Therefore, pregnant BALB/c females were treated subcutaneously with a single dose of VPA (500 mg/kg) or saline on gestational day 12.5. Male offspring mice were orally treated with the ARE from Portuguese blueberries (30 mg/kg/day) or the vehicle for three weeks, and further subjected to behavioral tests and biochemical analysis. Our data suggested that the ARE treatment alleviated autism-like behaviors in in utero VPA-exposed mice and, at the same time, decreased both neuroinflammation and gut inflammation, modulated the gut microbiota composition, increased serotonin levels in cerebral prefrontal cortex and gut, and reduced the synaptic dysfunction verified in autistic mice. Overall, our work suggests that anthocyanins extracted from Portuguese blueberries could constitute an effective strategy to ameliorate typical autistic behaviors through modulation of the microbiota-gut-brain axis.

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.

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.

Strategies used by nature to fix the red, purple and blue colours in plants: a physical chemistry approach.

While identified by the respective flavylium cation, anthocyanins are much more than this molecule. The flavylium cation (generally appearing only at very acidic pH values) is one of the molecules of a complex sequence of pH dependent molecular species reversibly interconnected by different chemical reactions. These species include the red flavylium cation, purple quinoidal base and blue or bluish anionic quinoidal bases. At the common pH of the vacuoles of simpler anthocyanins, the red flavylium cation is present only at very acidic pH values and at moderately acidic pHs there is no significant colour of the purple quinoidal base. Moreover, the blue or bluish anionic quinoidal base appearing around neutral pH values is not stable. Intermolecular (copigmentation) and intramolecular (in acylated anthocyanins) interactions increase the colour hue and yield bathochromic shifts in the absorption bands, permitting to extend the pH domain of the flavylium cation and increase the mole fraction of the quinoidal bases. Metal complexation is another strategy. In particular, the Al3+ cation plays an essential role in the blue colour of hydrangea. The most sophisticated structures are however the metaloanthocyanins, such as the one that gives the blue colour of commelina communis, constituted of six anthocyanins, six flavanones and two metals. In this work we discuss how physical chemical tools are indispensable to account for the chemical behaviour of these complex systems. The experimental procedures and the equations needed to calculate all equilibrium constants of anthocyanins and the consequent pH dependent mole fraction distributions in the absence or presence of copigments are described in detail. Reverse pH jumps monitored by stopped flow have been shown to be an indispensable tool to calculate these parameters.

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.

Anthocyanin Color Stabilization by Host-Guest Complexation with p-Sulfonatocalix[n]arenes.

Flavylium-based compounds in their acidic and cationic form bring color to aqueous solutions, while under slightly acidic or neutral conditions they commonly bring discoloration. Selective host-guest complexation between water-soluble p-sulfonatocalix[n]arenes (SCn) macrocycles and the flavylium cationic species can increase the stability of the colored form, expanding its domain over the pH scale. The association constants between SCn and the cationic (acid) and neutral basic forms of flavylium-based compounds were determined through UV-Vis host-guest titrations at different pH values. The affinity of the hosts for synthetic chromophore was found to be higher than for a natural anthocyanin (Oenin). The higher affinity of SC4 for the synthetic flavylium was confirmed by 1H NMR showing a preferential interaction of the flavylium phenyl ring with the host cavity. In contrast with its synthetic counterpart, the flavylium substitution pattern in the anthocyanin seems to limit the inclusion of the guest in the host's binding pocket. In this case, the higher affinity was observed for the octamer (SC8) likely due to its larger cavity and higher number of negatively charged sulfonate groups.

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.

An Insight into Kiwiberry Leaf Valorization: Phenolic Composition, Bioactivity and Health Benefits.

During kiwiberry production, different by-products are generated, including leaves that are removed to increase the fruit's solar exposure. The aim of this work was to extract bioactive compounds from kiwiberry leaf by employing microwave-assisted extraction (MAE). Compatible food solvents (water and ethanol) were employed. The alcoholic extract contained the highest phenolic and flavonoid contents (629.48 mg of gallic acid equivalents (GAE) per gram of plant material on dry weight (dw) (GAE/g dw) and 136.81 mg of catechin equivalents per gram of plant material on dw (CAE/g dw), respectively). Oppositely, the hydroalcoholic extract achieved the highest antioxidant activity and scavenging activity against reactive oxygen and nitrogen species (IC50 = 29.10 µg/mL for O2•-, IC50 = 1.87 µg/mL for HOCl and IC50 = 1.18 µg/mL for •NO). The phenolic profile showed the presence of caffeoylquinic acids, proanthocyanidin, and quercetin in all samples. However, caffeoylquinic acids and quercetin were detected in higher amounts in the alcoholic extract, while proanthocyanidins were prevalent in the hydroalcoholic extract. No adverse effects were observed on Caco-2 viability, while the highest concentration (1000 µg/mL) of hydroalcoholic and alcoholic extracts conducted to a decrease of HT29-MTX viability. These results highlight the MAE potentialities to extract bioactive compounds from kiwiberry leaf.