Dearomatization drives complexity generation in freshwater organic matter.

Dissolved organic matter (DOM) is one of the most complex, dynamic and abundant sources of organic carbon, but its chemical reactivity remains uncertain1-3. Greater insights into DOM structural features could facilitate understanding its synthesis, turnover and processing in the global carbon cycle4,5. Here we use complementary multiplicity-edited 13C nuclear magnetic resonance (NMR) spectra to quantify key substructures assembling the carbon skeletons of DOM from four main Amazon rivers and two mid-size Swedish boreal lakes. We find that one type of reaction mechanism, oxidative dearomatization (ODA), widely used in organic synthetic chemistry to create natural product scaffolds6-10, is probably a key driver for generating structural diversity during processing of DOM that are rich in suitable polyphenolic precursor molecules. Our data suggest a high abundance of tetrahedral quaternary carbons bound to one oxygen and three carbon atoms (OCqC3 units). These units are rare in common biomolecules but could be readily produced by ODA of lignin-derived and tannin-derived polyphenols. Tautomerization of (poly)phenols by ODA creates non-planar cyclohexadienones, which are subject to immediate and parallel cycloadditions. This combination leads to a proliferation of structural diversity of DOM compounds from early stages of DOM processing, with an increase in oxygenated aliphatic structures. Overall, we propose that ODA is a key reaction mechanism for complexity acceleration in the processing of DOM molecules, creation of new oxygenated aliphatic molecules and that it could be prevalent in nature.

Polyphenolic Nanoparticle Platforms (PARCELs) for In Vitro and In Vivo mRNA Delivery.

Despite their successful implementation in the COVID-19 vaccines, lipid nanoparticles (LNPs) still face a central limitation in the delivery of mRNA payloads: endosomal trapping. Improving upon this inefficiency could afford improved drug delivery systems, paving the way toward safer and more effective mRNA-based medicines. Here, we present polyphenolic nanoparticle platforms (PARCELs) as effective mRNA delivery systems. In brief, our investigation begins with a computationally guided structural analysis of 1825 discrete polyphenolic structural data points across 73 diverse small molecule polyphenols and 25 molecular parameters. We then generate structurally diverse PARCELs, evaluating their in vitro mechanism and activity, ultimately highlighting the superior endosomal escape properties of PARCELs relative to analogous LNPs. Finally, we examine the in vivo biodistribution, protein expression, and therapeutic efficacy of PARCELs in mice. In undertaking this approach, the goal of this study is to establish PARCELs as viable delivery platforms for safe and effective mRNA delivery.

Recent Progress in Protein-Polyphenol Assemblies for Biomedical Applications.

Nowadays, natural materials as smart building blocks for assembling functional materials have aroused extensive interest in the scientific community. Proteins and polyphenols are typical natural building blocks that are widely used. On the one hand, proteins are one of the most versatile classes of biomolecules, serving as catalysts, signaling molecules, transporters, receptors, scaffolds that maintain the integrity of cell and tissue, and more. On the other hand, the facile adhesion of naturally abundant polyphenols with other substances and their potential biomedical applications have been highly attractive for functional biomaterials fabrication. Additionally, there are a variety of interactions between the proteins and polyphenols, mainly hydrogen bonding, hydrophobic, and ionic interactions. These reversible dynamic interactions enable proteins and polyphenols to form stable protein-polyphenol assemblies and maintain their inherent structures and biological activities in the assemblies. Therefore, protein-polyphenol assemblies can be applied to design a variety of advanced functional materials for biomedical applications. Herein, recent progress in protein-polyphenol particles, capsules, coatings, and hydrogels is summarized, the preparation and application of these assemblies are introduced in detail, and the future of the field is prospected.

Synthesis of MOF-5/polyethersulfone (PES) mixed matrix membranes for enhancing membrane filtration performance in polyphenol purification.

The various apple products industries produce a large amount of apple residue, which is easily fermented, causes environmental pollution, and its disposal cost is high, but is rich in nutrients, such as polyphenols. Polyphenols can be purified to realize high-value deep processing of apple pomace and to promote energy reuse of food waste. In this study, the highly selective purification of polyphenols was achieved by membrane filtration using prepared Metal-organic framework (MOF)-5/PES mixed matrix membranes with apple peels as raw material. The polyethersulfone mixed matrix membrane was loaded with MOF-5 by the phase inversion method, and their structural and physicochemical properties were characterized by scanning electron microscopy (SEM), and X-ray diffraction (XRD). Zeta potential and specific surface area of MOF-5 particles were measured, as well as the water contact angle and anti-fouling properties of the mixed matrix membrane were analyzed. It was confirmed that the membrane loaded with MOF-5 showed better hydrophilicity and mechanical properties compared with the pristine polyether sulfone membrane. Under practical conditions, the increased hydrophilicity could enhance the anti-fouling properties of membranes, which would improve the flux recovery ratio of membranes. In addition, the prepared MOF-5/PES mixed matrix membrane was applied to the purification of polyphenols, showing excellent purification performance of polyphenols. In particular, the purity of polyphenol after membrane filtration could reach 70.45% when the additional amount of MOF-5 was 10%. This research provides a method to prepare MOF-5/PES mixed matrix membranes, which effectively solves the problem of unstable and unsatisfactory purification effect of commercially available membranes, promotes the development of new materials in membrane science, and realizes high-value deep processing and comprehensive resource development of food waste using membrane filtration.

Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders.

Metabolic disorders (MDs), including dyslipidemia, non-alcoholic fatty liver disease, diabetes mellitus, obesity and cardiovascular diseases are a significant threat to human health, despite the many therapies developed for their treatment. Different classes of bioactive compounds, such as polyphenols, flavonoids, alkaloids, and triterpenes have shown therapeutic potential in ameliorating various disorders. Most of these compounds present low bioavailability when administered orally, being rapidly metabolized in the digestive tract and liver which makes their metabolites less effective. Moreover, some of the bioactive compounds cannot fully exert their beneficial properties due to the low solubility and complex chemical structure which impede the passive diffusion through the intestinal cell membranes. To overcome these limitations, an innovative delivery system of phytosomes was developed. This review aims to highlight the scientific evidence proving the enhanced therapeutic benefits of the bioactive compounds formulated in phytosomes compared to the free compounds. The existing knowledge concerning the phytosomes' preparation, their characterization and bioavailability as well as the commercially available phytosomes with therapeutic potential to alleviate MDs are concisely depicted. This review brings arguments to encourage the use of phytosome formulation to diminish risk factors inducing MDs, or to treat the already installed diseases as complementary therapy to allopathic medication.

Graphene and Natural Products: A Review of Antioxidant Properties in Graphene Oxide Reduction.

This review article addresses the antioxidant properties of different natural products, including ascorbic acid, gallic acid, oxalic acid, L-glutathione (GSH), bacteriorhodopsin, green tea polyphenols, glucose, hydroxycinnamic acid, ethanoic acid, betanin, and L-glutathione, in the reduction of graphene oxide (rGO). rGO can cause damage to cells, including oxidative stress and inflammation, limiting its application in different sectors that use graphene, such as technologies used in medicine and dentistry. The natural substances reviewed have properties that help reduce this damage, neutralizing free radicals and maintaining cellular integrity. This survey demonstrates that the combination of these antioxidant compounds can be an effective strategy to minimize the harmful effects of rGO and promote cellular health.

Highly Adhesive Amyloid-Polyphenol Hydrogels for Cell Scaffolding.

Rationally designing microstructures of soft hydrogels for specific biological functionalization is a challenge in tissue engineering applications. A novel and affordable soft hydrogel scaffold is constructed here by incorporating polyphenol modules with lysozyme amyloid fibrils (Lys AFs) via non-covalent self-assembly. Embedded polyphenols not only trigger hydrogel formation but also determine gel behavior by regulating the polyphenol gallol density and complex ratio. The feasibility of using a polyphenol-Lys AF hydrogel as a biocompatible cell scaffold, which is conducive to cell proliferation and spreading, is also shown. Notably, introducing polyphenols imparts the corresponding hydrogels a superior cell bioadhesive efficiency without further biofunctional decoration and thus may be successfully employed in both healthy and cancer cell lines. Confocal laser scanning microscopy also reveals that the highly expressed integrin-mediated focal adhesions form due to stimulation of the polyphenol-AF composite hydrogel, direct cell adhesion, proliferation, and spreading. Overall, this work constitutes a significant step forward in creating highly adhesive tissue culture platforms for in vitro culture of different cell types and may greatly expand prospects for future biomaterial design and development.

Processing Stabilization of Polyethylene with Grape Peel Extract: Effect of Extraction Technology and Composition.

Dry grape peel powder was extracted by three different techniques, stirred tank reactor, Soxhlet and ultrasound extraction. The composition, physical and chemical structure and inherent stability of the extracts were characterized by various methods. The extracts and reference compounds were added to polyethylene and their stabilization efficiency was determined in multiple extrusion experiments. The composition of the extracts was quite similar. Ten main compounds were identified in the extracts, which contained a considerable number of polyphenols, but only small amounts of quercetin and trans-resveratrol. The extracts proved to be more efficient processing stabilizers than trans-resveratrol and the commercial stabilizer, Irganox 1010, irrespective of the extraction technology used. In spite of their good processing stabilization effect, polymers containing the extracts had poor residual stability. The differences in processing and long-term stabilization must be related to the different structures of the polyphenols contained by the extracts and the reference compounds. The results clearly prove that the IC50 value determined by the DPPH assay is not suitable for the estimation of the efficiency of a compound as a stabilizer for polymers.

Assembly of Hexagonal Column Interpenetrated Spheres from Plant Polyphenol/Cationic Surfactants and Their Application as Antimicrobial Molecular Banks.

Microbial infections have become a great threat to human health and one of the main risks arises from direct contact with the surfaces contaminated by pathogenic microbes. Herein, a kind of hexagonal column interpenetrated spheres (HCISs) are fabricated by non-covalent assembly of plant gallic acid with quaternary ammonium surfactants. Different from one-time burst release of conventional antimicrobial agents, the HCIS acts like a "antimicrobial molecular bank" and releases the antimicrobial ingredients in a multistage way, leading to long-lasting antimicrobial performance. Taking advantage of strong hydrophobicity and adhesion, HCISs are applicable to various substrates and endowed with anti-water washing property, thus showing high in vitro antimicrobial efficiency (>99 %) even after being used for 10 cycles. Meanwhile, HCISs exhibit broad-spectrum antimicrobial activity against bacteria and fungi, and have good biocompatibility with mammalian cells. Such a low-cost and portable long-lasting antimicrobial agent meets the growing anti-infection demand in public spaces.

Polyphenol stabilized copper nanoparticle formulations for rapid disinfection of bacteria and virus on diverse surfaces.

Rapid and sustained disinfection of surfaces is necessary to check the spread of pathogenic microbes. The current study proposes a method of synthesis and use of copper nanoparticles (CuNPs) for contact disinfection of pathogenic microorganisms. Polyphenol stabilized CuNPs were synthesized by successive reductive disassembly and reassembly of copper phenolic complexes. Morphological and compositional characterization by transmission electron microscope (TEM), selected area diffraction and electron energy loss spectroscopy revealed monodispersed spherical (ϕ5-8 nm) CuNPs with coexisting Cu, Cu(I) and Cu (II) phases. Various commercial grade porous and non-porous substrates, such as, glass, stainless steel, cloth, plastic and silk were coated with the nanoparticles. Complete disinfection of 107copies of surrogate enveloped and non-enveloped viruses: bacteriophage MS2, SUSP2, phi6; and gram negative as well as gram positive bacteria:Escherichia coliandStaphylococcus aureuswas achieved on most substrates within minutes. Structural cell damage was further analytically confirmed by TEM. The formulation was well retained on woven cloth surfaces even after repeated washing, thereby revealing its promising potential for use in biosafe clothing. In the face of the current pandemic, the nanomaterials developed are also of commercial utility as an eco-friendly, mass producible alternative to bleach and alcohol based public space sanitizers used today.

A new method of extracting polyphenols from honey using a biosorbent compared to the commercial resin amberlite XAD2.

A new extraction method of polyphenols from honey using a biodegradable resin was developed and compared with the common commercial resin amberlite XAD2. For this purpose, three honey samples of Algerian origin were selected for the different physicochemical and biochemical parameters study. After extraction of the target compounds by both resins, the polyphenol content was determined, the antioxidant activity was tested, and liquid chromatography-mass spectrometry analyses were performed for identification and quantification. The results showed that physicochemical and biochemical parameters meet the norms of the International Honey Commission, and the H1 sample seemed to be of high quality. The optimal conditions of extraction by biodegradable resin were a pH of 3, an adsorption dose of 40 g/L, a contact time of 50 min, an extraction temperature of 60°C, and no stirring. The regeneration and reuse number of both resins was three cycles. The polyphenol contents demonstrated a higher extraction efficiency of biosorbent than of XAD2, especially in H1. Liquid chromatography-mass spectrometry analyses allowed for the identification and quantification of 15 compounds in the different honey samples extracted using both resins and the most abundant compound was 3,4,5-trimethoxybenzoic acid. In addition, the biosorbent extracts showed stronger antioxidant activities than the XAD2 extracts.

Microfibrillated cellulose films containing chitosan and tannic acid for wound healing applications.

The effectiveness of tannic acid as antimicrobial and wound healing for burns have been shown for a century; however, uncontrolled target dosage may result in undesirable side-effects. Remarkably, tannic acid polyphenols compounds crosslinked with polymeric materials produce a strong composite containing the beneficial properties of this tannin. However, investigation of the crosslink structure and its antibacterial and regenerative properties are still unknown when using nanocellulose by mechanical defibrillation; additionally, due to the potential crosslink structure with chitosan, its structure can be complex. Therefore, this work uses bleach kraft nanocellulose in order to investigate the effect on the physical and regenerative properties when incorporated with chitosan and tannic acid. This film results in increased rigidity with a lamellar structure when incorporated with tannic acid due to its strong hydrogen bonding. The release of tannic acid varied depending on the structure it was synthesised with, whereas with chitosan it presented good release model compared to pure cellulose. In addition, exhibiting similar thermal stability as pure cellulose films with antibacterial properties tested against S. aureus and E. coli with good metabolic cellular viability while also inhibiting NF-κB activity, a characteristic of tannic acid.

Basic Methods for Preparation of Liposomes and Studying Their Interactions with Different Compounds, with the Emphasis on Polyphenols.

Studying the interactions between lipid membranes and various bioactive molecules (e.g., polyphenols) is important for determining the effects they can have on the functionality of lipid bilayers. This knowledge allows us to use the chosen compounds as potential inhibitors of bacterial and cancer cells, for elimination of viruses, or simply for keeping our healthy cells in good condition. As studying those effect can be exceedingly difficult on living cells, model lipid membranes, such as liposomes, can be used instead. Liposomal bilayer systems represent the most basic platform for studying those interactions, as they are simple, quite easy to prepare and relatively stable. They are especially useful for investigating the effects of bioactive compounds on the structure and kinetics of simple lipid membranes. In this review, we have described the most basic methods available for preparation of liposomes, as well as the essential techniques for studying the effects of bioactive compounds on those liposomes. Additionally, we have provided details for an easy laboratory implementation of some of the described methods, which should prove useful especially to those relatively new on this research field.

Resveratrol-Encapsulated Mitochondria-Targeting Liposome Enhances Mitochondrial Respiratory Capacity in Myocardial Cells.

The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic ß cells (ß-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the ß-MEND (ß-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells). The ß-MEND (RES) was readily taken up by H9c2 cells, as verified by fluorescence-activated cell sorter data, and was observed to be colocalized with intracellular mitochondria by confocal laser scanning microscopy. Myocardial mitochondrial function was evaluated by a Seahorse XF Analyzer and the results showed that the ß-MEND (RES) significantly activated cellular maximal respiratory capacity. In addition, the ß-MEND (RES) showed no cellular toxicity for H9c2 cells as evidenced by Premix WST-1 assays. This is the first report of the use of a myocardial mitochondria-targeting liposome encapsulating RES for activating mitochondrial function, which was clearly confirmed based on analyses using a Seahorse XF Analyzer.

Innovative Combination of Dispersive Solid Phase Extraction Followed by NIR-Detection and Multivariate Data Analysis for Prediction of Total Polyphenolic Content.

Recently polyphenols attracted great interest in the field of food and nutrition as well as in the pharmaceutical and cosmetics industries due to their health benefits through antioxidative behavior in the human body. However, because of the high number of compounds characterized as phenols and their structural diversity, quantification of polyphenols turns out to be a highly complex task. Although, a wide variety of analytical methods are used for the determination of total polyphenolic content, they are all found to be lacking in a variety of different tasks, such as their limits of detection and quantification, repeatability, accuracy and specificity. For this reason, a novel approach combining the advantages of solid phase purification, near infrared analysis and multivariate data analysis was investigated for the prediction of total polyphenolic content, suitable for a wide range of sample matrices. Dispersive solid phase extraction was performed and optimized using polyvinylpyrrolidone as sorbent, known to selectively bind polyphenols. Near-infrared detection of adsorbed polyphenols was carried out subsequently. Furthermore, the method was in-house validated, examining selectivity, repeatability and accuracy, working range, as well as multivariate limit of detection and limit of quantification, comparing it with two routinely used methods-namely, Folin-Ciocalteu photometric assay and Löwenthal titration. The novel established method was applied for the prediction of total polyphenolic content in tea and wine samples.

Thermochemical Liquefaction as a Cleaner and Efficient Route for Valuing Pinewood Residues from Forest Fires.

Biomass thermochemical liquefaction is a chemical process with multifunctional bio-oil as its main product. Under this process, the complex structure of lignocellulosic components can be hydrolysed into smaller molecules at atmospheric pressure. This work demonstrates that the liquefaction of burned pinewood from forest fires delivers similar conversion rates into bio-oil as non-burned wood does. The bio-oils from four burned biomass fractions (heartwood, sapwood, branches, and bark) showed lower moisture content and higher HHV (ranging between 32.96 and 35.85 MJ/kg) than the initial biomasses. The increased HHV resulted from the loss of oxygen, whereas the carbon and hydrogen mass fractions increased. The highest conversion of bark and heartwood was achieved after 60 min of liquefaction. Sapwood, pinewood, and branches reached a slightly higher conversion, with yields about 8% greater, but with longer liquefaction time resulting in higher energy consumption. Additionally, the van Krevelen diagram indicated that the produced bio-oils were closer and chemically more compatible (in terms of hydrogen and oxygen content) to the hydrocarbon fuels than the initial biomass counterparts. In addition, bio-oil from burned pinewood was shown to be a viable alternative biofuel for heavy industrial applications. Overall, biomass from forest fires can be used for the liquefaction process without compromising its efficiency and performance. By doing so, it recovers part of the lost value caused by wildfires, mitigating their negative effects.

Oenothein B in Eucalyptus Leaf Extract Suppresses Fructose Absorption in Caco-2 Cells.

Inhibition of fructose absorption may suppress adiposity and adiposity-related diseases caused by fructose ingestion. Eucalyptus leaf extract (ELE) inhibits intestinal fructose absorption (but not glucose absorption); however, its active compound has not yet been identified. Therefore, we evaluated the inhibitory activity of ELE obtained from Eucalyptus globulus using an intestinal fructose permeation assay with the human intestinal epithelial cell line Caco-2. The luminal sides of a cell monolayer model cultured on membrane filters were exposed to fructose with or without the ELE. Cellular fructose permeation was evaluated by measuring the fructose concentration in the medium on the basolateral side. ELE inhibited 65% of fructose absorption at a final concentration of 1 mg/mL. Oenothein B isolated from the ELE strongly inhibited fructose absorption; the inhibition rate was 63% at a final concentration of 5 µg/mL. Oenothein B did not affect glucose absorption. In contrast, the other major constituents (i.e., gallic acid and ellagic acid) showed little fructose-inhibitory activity. To our knowledge, this is the first report that oenothein B in ELE strongly inhibits fructose absorption in vitro. ELE containing oenothein B can prevent and ameliorate obesity and other diseases caused by dietary fructose consumption.

Optimization of Two Eco-Friendly Extractions of Black Medick (Medicago lupulina L.) Phenols and Their Antioxidant, Cosmeceutical, α-Glucosidase and α-Amylase Inhibitory Properties.

Medicago lupulina is an ancient edible plant from the Fabaceae family. In this work, two eco-friendly methods for extraction of bioactive phenolics from M. lupulina were developed using mixtures of water with two non-toxic, skin- and environmentally-friendly polyol solvents: glycerol and polypropylene glycol. Ultrasound-assisted extractions were optimized using a Box-Behnken design. The independent variables were the concentration of organic solvent in water (X1), extraction temperature (X2) and time (X3), while the response was phenolic content. The optimum conditions for extraction of polyphenols were (X1, X2, X3): (45%, 70 °C, 60 min) and (10%, 80 °C, 60 min) for glycerol and polypropylene glycol extraction, respectively. The extracts prepared at optimum conditions were rich in phenolic compounds, mainly derivatives of apigenin, kaempferol, luteolin, quercetin, caffeic and ferulic acid, as well as coumestrol. Their cosmeceutical and antidiabetic activity was tested. Both extracts demonstrated notable antioxidant, anti-lipoxygenase and anti-α-amylase activity. In addition to those activities, the glycerol extract efficiently inhibited protein coagulation, elastase and α-glucosidase activity. Glycerol present in the extract displayed enzyme-inhibiting activity in several assays and supported the action of the bioactive constituents. Thus, the optimized glycerol extract is a desirable candidate for direct incorporation in antidiabetic food supplements and cosmeceutical products.

A Review on Obesity Management through Natural Compounds and a Green Nanomedicine-Based Approach.

Obesity is a serious health complication in almost every corner of the world. Excessive weight gain results in the onset of several other health issues such as type II diabetes, cancer, respiratory diseases, musculoskeletal disorders (especially osteoarthritis), and cardiovascular diseases. As allopathic medications and derived pharmaceuticals are partially successful in overcoming this health complication, there is an incessant need to develop new alternative anti-obesity strategies with long term efficacy and less side effects. Plants harbor secondary metabolites such as phenolics, flavonoids, terpenoids and other specific compounds that have been shown to have effective anti-obesity properties. Nanoencapsulation of these secondary metabolites enhances the anti-obesity efficacy of these natural compounds due to their speculated property of target specificity and enhanced efficiency. These nanoencapsulated and naive secondary metabolites show anti-obesity properties mainly by inhibiting the lipid and carbohydrate metabolizing enzymes, suppression of adipogenesis and appetite, and enhancing energy metabolism. This review focuses on the plants and their secondary metabolites, along with their nanoencapsulation, that have anti-obesity effects, with their possible acting mechanisms, for better human health.

Use of water and ethanol extracts from wine grape seed pomace to prepare an antioxidant toothpaste.

BACKGROUND: Extracts of fresh wine grape seeds/skin or of grape pomace seeds were used to prepare antioxidant natural toothpastes. RESULTS: Ethanol extracted twice more polyphenols than water; ultrasound did not provide any improvement in the extraction. The addition of freeze-dried ethanol extracts of seeds or skin, at 2% and 10%, to the commercial toothpaste significantly increased the polyphenol content, both from white grape seeds and skin and from red grape seed pomace. The evaluation of time stability (shelf life) revealed a decrease, after 4 months, of 3.9% and 9.4% in total polyphenol content, in 5% and 10% water extracts, but not for ethanol extracts. 1,1-Diphenyl-2-picrilhydrazil1 antiradical activity was the highest in 10% of seed water extract toothpaste and, after 4 months, the activity was stable. CONCLUSION: Ethanol and water are efficient and safe solvents to create natural toothpaste with grape or pomace seed extract with antioxidant activity. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.