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.

Polyphenol-Enabled 2D Nanopatch for Enhanced Nasal Mucoadhesion and Immune Activation.

The advancement of effective nasal mucoadhesive delivery faces challenges due to rapid mucociliary clearance (MCC). Conventional studies have employed mucoadhesive materials, mainly forming spherical nanoparticles, but these offer limited adhesion to the nasal mucosa. This study hypothesizes that a 2D nanoscale structure utilizing adhesive polyphenols can provide a superior strategy for countering MCC, aligning with the planar mucosal layers. We explore the use of tannic acid (TA), a polyphenolic molecule known for its adhesive properties and ability to form complexes with biomolecules. Our study introduces an unprecedented 2D nanopatch, assembled through the interaction of TA with green fluorescent protein (GFP), and cell-penetrating peptide (CPP). This 2D nanopatch demonstrates robust adhesion to nasal mucosa and significantly enhances immunoglobulin A secretions, suggesting its potential for enhancing nasal vaccine delivery. The promise of a polyphenol-enabled adhesive 2D nanopatch signifies a pivotal shift from conventional spherical nanoparticles, opening new pathways for delivery strategies through respiratory mucoadhesion.

Change in Nfkb/Nrf2/Bax Levels by High Monomeric Polyphenols Berries Extract (HMPBE) in Acute and Chronic Secondary Brain Damage.

BACKGROUND/AIMS: High Monomeric Polyphenols Berries Extract (HMPBE) is a formula highly rich in polyphenols clinically proven to enhance learning and memory. It is currently used to enhances cognitive performance including accuracy, working memory and concentration. METHODS: Here, we investigated for the first time the beneficial effects of HMPBE in a mouse model of acute and chronic traumatic brain injury (TBI). RESULTS: HMPBE, at the dose of 15 mg/kg was able to reduce histological alteration as well as inflammation and lipid peroxidation. HMPBE ameliorate TBI by improving Nrf-2 pathway, reducing Nf-kb nuclear translocation and apoptosis, and ameliorating behavioral alteration such as anxiety and depression. Moreover, in the chronic model of TBI, HMPBE administration restored the decline of Tyrosine Hydroxylase (TH) and dopamine transporter (DAT) and the accumulation of a-synuclein into the midbrain region. This finding correlates the beneficial effect of HMPBE administration with the onset of parkinsonism related to traumatic brain damage. CONCLUSION: The data may open a window for developing new support strategies to limit the neuroinflammation event of acute and chronic TBI.

Smart Enzyme-Like Polyphenol-Copper Spray for Enhanced Bacteria-Infected Diabetic Wound Healing.

Developing functional medical materials is urgent to treat diabetic wounds with a high risk of bacterial infections, high glucose levels and oxidative stress. Here, a smart copper-based nanocomposite acidic spray has been specifically designed to address this challenge. This copper-based nanocomposite is pH-responsive and has multienzyme-like properties. It enables the spray to effectively eliminate bacteria and alleviate tissue oxidative pressure, thereby accelerating the healing of infected diabetic wounds. The spray works by generating hydroxyl radicals through catalysing H2O2, which has a high sterilization efficiency of 97.1%. As alkaline micro-vessel leakage neutralizes the acidic spray, this copper-based nanocomposite modifies its enzyme-like activity to eliminate radicals. This reduces the level of reactive oxygen species in diabetic wounds by 45.3%, leading to a similar wound-healing effect between M1 diabetic mice and non-diabetic ones by day 8. This smart nanocomposite spray provides a responsive and regulated microenvironment for treating infected diabetic wounds. It also offers a convenient and novel approach to address the challenges associated with diabetic wound healing.

Sonochemical Synthesis of Natural Polyphenolic Nanoparticles for Modulating Oxidative Stress.

Natural polyphenolic compounds play a vital role in nature and are widely utilized as building blocks in the fabrication of emerging functional nanomaterials. Although diverse fabrication methodologies are developed in recent years, the challenges of purification, uncontrollable reaction processes and additional additives persist. Herein, a modular and facile methodology is reported toward the fabrication of natural polyphenolic nanoparticles. By utilizing low frequency ultrasound (40 kHz), the assembly of various natural polyphenolic building blocks is successfully induced, allowing for precise control over the particle formation process. The resulting natural polyphenolic nanoparticles possessed excellent in vitro antioxidative abilities and in vivo therapeutic effects in typical oxidative stress models including wound healing and acute kidney injury. This study opens new avenues for the fabrication of functional materials from naturally occurring building blocks, offering promising prospects for future advancements in this field.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Polyphenol-Assisted Biomineralization of Metal-Organic Framework Nanoparticles for Precision Delivery of Therapeutic Proteins to Cancer Cells.

The delivery of proteins into the cytosol holds great promise for cell signaling manipulation and the development of precision medicine. However, this potency is challenged by achieving targeted and controlled delivery, specifically within diseased cells. In this study, we introduce a versatile and effective method for the precision delivery of therapeutic proteins to cancer cells by designing polyphenol-assisted biomineralization of zeolite imidazole framework-8 (ZIF-8). We demonstrate that by leveraging the strong noncovalent binding affinity of epigallocatechin gallate (EGCG) with both proteins and ZIF-8, our approach significantly enhances the biomineralization of ZIF-8, which in turn improves the efficiency of protein encapsulation and intracellular delivery. Moreover, the incorporation of EGCG within ZIF-8 enables controlled degradation of the nanoparticles and the selective release of the encapsulated proteins in cancer cells. This selective release is triggered by the oxidation of EGCG in response to the high levels of reactive oxygen species (ROS) found within cancer cells that destabilize the EGCG/ZIF-8 nanoparticles. We have further demonstrated the ability of EGCG/ZIF-8 to deliver a wide range of proteins into cancer cells, including bacterial virulence protein, to rewire cell signaling and prohibit tumor cell growth in a mouse xenograft model. Our strategy and findings underscore the potential of designing the EGCG/ZIF-8 interface for specific and controlled protein delivery for targeted cancer therapy.

High quality RNA extraction protocol for polyphenolics-rich Cotton tissue.

The extraction of high-quality RNA from cotton (Gossypium spp.) is challenging because of the presence of high polyphenolics, polysaccharides, quinones, and other secondary metabolites. A high-throughput RNA extraction protocol is a prerequisite. This Triton-X-100-based RNA extraction method utilizes Polyvinyl pyrrolidone polymer (PVPP) treatment which efficiently removes phenolics, and the application of Lithium chloride (LiCl) has been found that successfully precipitated the high-quality RNA from cotton tissue. Cytoplasmic male sterility (CMS) is a maternally inherited trait associated with specific mitochondrial genome rearrangements or mutations. The suitability of RNA extracted from Cotton CMS lines was assessed. cDNA was synthesized from RNA and assayed for mitochondrial genes (cox3, nad3, nad9) associated with male sterility. This paper discuss the advantages and limitation of this protocol over existing protocol for RNA extraction for polyphenolics-rich plant tissue.

Computational-Based Polyphenol Therapy for Nonsmall Cell Lung Cancer: Naringin Coamorphous Systems for Solubility and Bioavailability Enhancement.

In this research, we utilized molecular simulations to create co-amorphous materials (CAMs) of ceritinib (CRT) with the objective of improving its solubility and bioavailability. We identified naringin (NRG) as a suitable co-former for CRT CAMs based on binding energy and intermolecular interactions through computational modeling. We used the solvent evaporation method to produce CAMs of CRT and NRG, expecting to enhance both solubility and bioavailability simultaneously. The solid-state characterization using techniques like differential scanning calorimeter, X-ray powder diffraction, and Fourier-transform infrared spectroscopy affirmed the formation of a single amorphous phase and the presence of intermolecular interactions between CRT and NRG in the CAMs. These materials remained physically stable for up to six months under dry conditions at 40 °C. Moreover, the CAMs demonstrated significant improvements in the solubility and dissolution of CRT (specifically in the ratio CRT:NRG 1:2). This, in turn, led to an increase in cytotoxicity, apoptotic cells, and G0/G1 phase inhibition in A549 cells compared to CRT alone. Furthermore, CRT permeability is also improved twofold, as estimated by the everted gut sac method. The enhanced solubility of CAMs also positively affected the pharmacokinetic parameters. When compared to the physical mixture, the CAMs of CRT:NRG 2:1 exhibited a 2.1-fold increase in CRT exposure (AUC0-t) and a 2.4-fold increase in plasma concentration (Cmax).

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.

Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin.

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.

The role of artificial intelligence in the development of anticancer therapeutics from natural polyphenols: Current advances and future prospects.

Natural polyphenols, abundant in the human diet, are derived from a wide variety of sources. Numerous preclinical studies have demonstrated their significant anticancer properties against various malignancies, making them valuable resources for drug development. However, traditional experimental methods for developing anticancer therapies from natural polyphenols are time-consuming and labor-intensive. Recently, artificial intelligence has shown promising advancements in drug discovery. Integrating AI technologies into the development process for natural polyphenols can substantially reduce development time and enhance efficiency. In this study, we review the crucial roles of natural polyphenols in anticancer treatment and explore the potential of AI technologies to aid in drug development. Specifically, we discuss the application of AI in key stages such as drug structure prediction, virtual drug screening, prediction of biological activity, and drug-target protein interaction, highlighting the potential to revolutionize the development of natural polyphenol-based anticancer therapies.

In vitro inhibition of α-Synuclein aggregation and disaggregation of preformed fibers by polyphenol hybrids with 2-conjugated benzothiazole.

The misfolding and aggregation of α-Syn play a pivotal role in connecting diverse pathological pathways in Parkinson's disease (PD). Preserving α-Syn proteostasis and functionality by inhibiting its aggregation or disaggregating existing aggregates using suitable inhibitors represents a promising strategy for PD prevention and treatment. In this study, a series of benzothiazole-polyphenol hybrids was designed and synthesized. Three identified compounds exhibited notable inhibitory activities against α-Syn aggregation in vitro, with IC50 values in the low micromolar range. These inhibitors demonstrated sustained inhibitory effects throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation. Moreover, the compounds effectively disintegrated preformed α-Syn oligomers and fibers, potentially by binding to specific domains within the fibers, inducing fibril instability, collapse, and ultimately resulting in smaller-sized aggregates and monomers. These findings offer valuable insights into the therapeutic potential of polyphenol hybrids with 2-conjugated benzothiazole targeting α-Syn aggregation in the treatment of PD.

MPNTEXT: An Interactive Platform for Automatically Extracting Metal-Polyphenol Networks and Their Applications from Scientific Literature.

In recent years, metal-polyphenol networks (MPNs) have gained significant attention due to their unique properties and broad applications across various fields. However, the burgeoning volume of MPN literature necessitates the automation of chemical information extraction from the extensive corpus of unstructured data, including scientific publications. To address this challenge, we proposed a platform named MPNTEXT, which utilized natural language processing techniques and machine learning algorithms to efficiently identify and extract pertinent information, thereby assisting users in comprehending complex MPNs and their textual descriptions of applications. Users can enter keywords, such as "Fe", "drug delivery", or "tannic acid", to retrieve relevant information, which is then presented in a structured format. This study aims to provide a user-friendly tool for collecting and retrieving MPN data and promotes data-driven material design. The platform offers researchers a more convenient and efficient way to design versatile MPNs and explore their applications.

Glucose Uptake-Stimulating Metabolites from Aerial Parts of Centaurea sicula.

A comprehensive phytochemical investigation of aerial parts obtained from Centaurea sicula L. led to the isolation of 14 terpenoids (1-14) and nine polyphenols (15-23). The sesquiterpenoid group (1-11) included three structural families, namely, elemanolides (1-6), eudesmanolides (7 and 8), and germacranolides (9-11) with four unreported secondary metabolites (5-8), whose structure has been determined by extensive spectroscopic analysis, including 1D/2D NMR, HR-MS, and chemical conversion. Moreover, an unprecedented alkaloid, named siculamide (24), was structurally characterized, and a possible biogenetic origin was postulated. Inspired by the traditional use of the plant and in the frame of ongoing research on compounds with potential activity on metabolic syndrome, all the isolated compounds were evaluated for their stimulation of glucose uptake, disclosing remarkable activity for dihydrocnicin (10) and the lignan salicifoliol (15).

Effective α-glycosidase inhibitors based on polyphenolic benzothiazole heterocycles.

α-Glycosidase inhibition is one of the main approaches to treat Diabetes mellitus. Polyphenolic moieties are known to be responsible for yielding exhibit potent α-glycosidase inhibitory effects. In addition, compounds containing benzothiazole and Schiff base functionalities were previously reported to show α-glycosidase inhibition. In this paper, the synthesis of seven new phloroglucinol-containing benzothiazole Schiff base derivatives through the reaction of 6-substituted-2-aminobenzothiazole compounds with 2,4,6-trihydroxybenzaldehyde using acetic acid as a catalyst was reported. The synthesized compounds were characterized using spectroscopic methods such as FT-IR, 1H NMR, 13C NMR, and elemental analysis. The synthesized compounds were evaluated for their inhibitory effects on α-glycosidase, compounds 3f and 3g were found to show significant inhibitory properties when compared to the positive control. The IC50 values of 3f and 3g were calculated as 24.05 ± 2.28 and 18.51 ± 1.19 µM, respectively. Kinetic studies revealed that compounds 3f and 3g exhibited uncompetitive mode of inhibition against α-glycosidase. Molecular modeling predicted druglikeness for the title compounds and underpinned the importance of phloroglucinol hydroxyls for interacting with the key residues of α-glycosidase.

Structures, biosynthesis and biological activities of benastatins, anthrabenzoxocinones and fredericamycins.

The fast spread of antibiotic resistance results in the requirement for a constant introduction of new candidates. Pentangular polyphenols, a growing family of actinomycetes-derived aromatic type II polyketides, have attracted considerable attention due to their intriguing polycyclic systems and potent antimicrobial activity. Among them, benastatins, anthrabenzoxocinones (ABXs), and fredericamycins, display unique variations in their polycyclic frameworks, yet concurrently share structural commonalities within their substitutions. The present review summarizes advances in the isolation, spectroscopic characteristics, biosynthesis, and biological activities of pentangular polyphenols benastatins (1-16), ABXs (17-39), and fredericamycins (40-42) from actinomycetes. The information presented here thus prompts researchers to further explore and discover additional congeners within these three small classes of pentangular polyphenols.

Advanced application of tea residue extracts rich in polyphenols for enhancing sludge dewaterability: Unraveling the role of pH regulation.

Tea polyphenols (TPs), as a kind of derivatives from tea waste, were employed as a novel environmentally friendly bio-based sludge conditioner in this study. The findings showed that when TPs were applied at a dosage of 300 mg g-1 DS, the sludge CST0/CST ratio significantly increased to 1.90. pH regulation was found to markedly affect the dewatering efficiency of sludge. At pH 4, the CST0/CST rose to 2.86, coupled with a reduction in the specific resistance to filtration (SRF) from 6.69 × 1013 m kg-1 to 1.43 × 1013 m kg-1 and a decrease in the moisture content (MC) from 90.57% to 68.75%. TPs formed complexes and precipitated sludge proteins, as demonstrated by changes in the extracellular polymeric substances (EPS), viscosity, zeta potential, and particles size distribution. The optimization significance of acidification treatment on sludge structure disintegration, the interaction of TPs with EPS, and the removal of sludge proteins were elucidated. The research provided an ideal approach for the integrated utilization of biomass resources from tea waste and highlighted the potential application of TPs as an environmentally friendly conditioner in sludge dewatering.

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.