Polyphenols Research Articles

Preparation and Characterisation of High-Density Polyethylene/Tannic Acid Composites

This research paper highlights the preparation and characterisation of high-density polyethylene (HDPE)/tannic acid (TA) composites, designed to confer antioxidant properties to HDPE, valorising a biobased filler. Indeed, tannic acid is a natural polyphenol, demonstrating, among others, strong antioxidation properties. Using a melt-mixing process, HDPE/TA composites containing various amounts of TA, ranging between 1 and 20 wt%, were prepared, and analyses on their structural, thermal, mechanical, as well as antioxidant properties were conducted. Infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction showed that TA was successfully incorporated into the HDPE matrix. Thermogravimetric analysis evidenced that the onset of thermal degradation decreased, but overall satisfactory stability was observed. The composites exhibited exceptional antioxidant properties, especially the ones with the highest TA content, although it was observed that a high amount of TA had adverse effects on the mechanical performance of the composites.

Modulation of the receptor for advanced glycation end products pathway by natural polyphenols: A therapeutic approach to neurodegenerative diseases

Modulation of the receptor for advanced glycation end products pathway by natural polyphenols: A therapeutic approach to neurodegenerative diseases

Proanthocyanidin-Imbued Cellulosic 3-Dimentional Intrinsic Aligned Nanostructures: A Novel Approach for Dental and Bone Regeneration using Dental Pulp Derived Stem Cells

Developing effective scaffolds to address significant bone and dental defects is crucial in regenerative osteal and dental medicine. Traditional methods utilizing synthetic micropatterned scaffolds have effectively stimulated osteogenic and odontogenic differentiation of stem cells through parallel, 3D topographic, hexagonal, and elongated architectural features. However, these approaches face significant cost, scalability, and biocompatibility challenges. Recent advancements have highlighted the potential of decellularized plant scaffolds, such as those derived from Beaucarnea recurvata leaves (BLDS), which offer intrinsic microstructural advantages with solving reproducibility, scalability, incurred cost, and biocompatibility challenges. This study explores the enhancement of BLDS using grape seed proanthocyanidin extract (GSPE), a natural polyphenol known for its beneficial effects on bone and dental stem cell differentiation. By functionalizing BLDS with GSPE, we investigated its impact on osteogenic and odontogenic differentiation of human dental pulp-derived mesenchymal stem cells (DPDMSCs). The modified scaffolds exhibited improved physicochemical properties, including enhanced cell proliferation, protein absorption, scaffold interactions, and upregulated osteogenic and dental marker gene expression. SEM imaging revealed significant cellular growth and morphological changes indicative of successful differentiation. Furthermore, BLDS-GSPE demonstrated increased ALP activity and mineral deposition, suggesting its potential as a cost-effective, reproducible and biocompatible alternative for bone and dental repair compared to conventional synthetic biomaterials.

A Tannin–Oxidized Glucose Wood Adhesive with High Performance

Tannin, as a natural polyphenol found in plant sources, has been widely employed to replace petrol-based phenol to prepare tannin-based wood adhesives. However, the development of all-biomass tannin-based wood adhesive with superior bonding strength and water resistance is still a challenge. Herein, an all-biomass tannin-based adhesive was synthesized using tannin and glucose, demonstrating enhanced bonding strength and water resistance. To improve the reactivity of glucose, part of the hydroxyl groups on the glucose molecule is oxidized to aldehyde groups. The successful oxidation of glucose and synthesis of tannin-oxidized glucose (TOG) adhesive were demonstrated by Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). It was suggested that the improvement of TOG adhesive bonding properties and water resistance were caused by the formation of cross-linked network with covalent and hydrogen bonding synergies. The TOG adhesive has good water-resistance, and its residual rates can reach to 93.8% after soaking in water for 24h while the residual rates of tannin-glucose (T-G) adhesive only 81%. Compared with T-G and TOG adhesives, the dry bonding strength of adhesive increased by 256.5%, from 0.62MPa to 2.21MPa, the wet bonding strength of adhesive from zero to 1.97MPa. The plywood prepared with TOG adhesive met the GB/T 17657-2022 standard for Class II plywood. This study introduces an innovative and eco-friendly method for synthesizing an all-biomass tannin- based wood adhesive, characterized by superior bonding strength and enhanced water resistance.

Resveratrol Can Differentiate Human Melanoma Stem-like Cells from Spheroids Treated With All-trans Retinoic Acid.

Stem-like cancer cells are believed to be the leading cause of therapy resistance in malignant melanoma (MM). All-trans retinoic acid (ATRA) differentiation therapy is considered a promising approach to eradicate stem-like cancer cells, but some melanoma cells are resistant to ATRA. This study aimed to examine whether resveratrol (RS), a natural polyphenol compound, could improve the response of MM stem-like cells to ATRA and explore the possible underlying mechanisms. MM stem-like cells were established from a spheroid model of A375 human MM cell line. The response to RES alone and in combination with ATRA, was examined through analysis of cancer stemness, cell viability, and protein expression. The stem-like cells showed resistance to the anticancer drug docetaxel; however, the combination of RES and ATRA augmented the effects of docetaxel. Accordingly, these combinatorial effects were associated with significant inhibition of the expression levels of stemness markers CD133, OCT4, CD271, and ABCG2. The tested combinations also led to a significant increase in melanocyte differentiation marker SOX9, while efficiently suppressing the dedifferentiation marker SOX10. Notably, RES alone effectively up-regulated retinoic acid receptor beta (RARβ) expression and down-regulated crucial mediators like DNMT1, polycomb-group proteins EZH2, and BMI-1, which mechanistically explain how RES enhanced the differentiation-inducing effects of ATRA. The resistance of MM stem-like cells to ATRA can be attenuated by RES and combined applications of ATRA and RES provide a promising strategy for MM treatment.

Deciphering the biophysical aspects of the interaction of 3,5,4'-trihydroxy-trans-stilbene with ribonuclease A: spectroscopic and computational studies.

Drug-receptor interaction is an important aspect in drug action, drug discovery, and pharmacological aspects. The molecule 3,5,4'-trihydroxy-trans-stilbene known as resveratrol is a natural polyphenol and exhibits diverse biological activities. Ribonuclease A catalyses the degradation of RNA by its ribonucleolytic activity. The report presents the binding interaction of resveratrol with RNase A using experimental and theoretical techniques. Experimental studies revealed the interaction strength of 104M-1 order with a single binding site. Resveratrol quenched the ribonuclease A fluorescence with a quenching constant of 104M-1 range. The accessible fraction of the fluorophore was found to be 0.75 besides non-radiative energy transfer from ribonuclease A to resveratrol. The donor-acceptor distance was 2.14nm from FRET calculations. No visible changes in the protein structure was evident from the circular dichroism studies. The interface residues involved in the interaction were obtained from docking studies. Further, the participation of the active site residues, His 12, His 119, and Lys 41 with interaction indicates the location of resveratrol near to the active site of ribonuclease A and indicates its possible potential to inhibit the ribonuclease A activity. The RMSD of less than 3Å indicates stable conformation of protein in the complex. The protein RMSF value in the complex less than 3Å shows no deviation of protein residues over time and thus suggests no conformational variation in the protein after binding.

Synergistic photothermal enhancement of the antibacterial activity of fibroin hydrogel by dual-directional crosslink strategy for efficient solar steam generation

Silk fibroin (SF) has attracted wide attention due to its excellent biocompatibility and versatile adjustability. The regeneration and reutilization of silk fibroin can efficiently utilize waste cocoons and silk. However, the regenerated SF hydrogels suffer from inadequate mechanical properties and lack inherent antibacterial capabilities, limiting their application in seawater desalination. This study achieved a novel hydrogel (STS@Fe) with photothermal antimicrobial activity, good mechanical property, and excellent durability using a green dual-directional crosslink and meso-reconstruction strategy. The metal-phenolic networks (MPN) were synthesized utilizing the natural plant polyphenol tannic acid (TA) and Fe3O4 nanoparticles. This research incorporated MPN into dissolved and regenerated silk fibroin and sodium alginate solution, enhanced mechanical properties through cryogenic salt precipitation, and prepared STS@Fe hydrogel. The inherent photothermal properties of Fe3O4 nanoparticles and TA complex, coupled with their synergistic effect under near-infrared radiation, can confer excellent photothermal-enhanced antibacterial activity to the fibroin hydrogel. The tensile strength of STS@Fe hydrogel is enhanced 31 times than that of traditional fibroin hydrogel, and its evaporation rate is 4.77 times higher than that of pure water evaporation. The hydrogel has an efficient seawater desalination rate and outstanding antibacterial properties in real seawater conditions. Moreover, The STS@Fe shows effective treatment capabilities for dyeing wastewater and oily saline water.

High-throughput screening-based design of multifunctional natural polyphenol nano-vesicles to accelerate diabetic wound healing

Oxidative stress is a major pathological factor that impedes the diabetic wound healing process. Procyanidins (PC) form nanoparticle-vesicles (PPNs) through hydrogen bonding and exhibit good drug delivery capability; however, their application in diabetic wounds is unsatisfactory. To meet the antioxidant needs for treating, high-throughput screening in the natural product library (NPL) under in vitro oxidative stress conditions was conducted to enhance the antioxidant activity of PPNs. HUVECs treated with tert-Butyl Hydroperoxide (TBHP) were established as screening model in vitro. Baicalein (BAI) was identified from over 600 products in the library as the most effective one to combat oxidative stress. Further study showed that PC and BAI may react in equal proportions to synthesize new vesicles, named BAI-PC Polyphenolic nanovesicles (BPPNs), which possess reactive oxygen species (ROS) responsive and antioxidant effects. Network pharmacology indicated that in diabetic wounds, the target genes of PC are mainly enriched in the vascular endothelial growth factor (VEGF)-related pathways, while BAI primarily regulates tyrosine phosphorylation. The complementarity between the two has been validated in both in vitro and in vivo experiments. In summary, the antioxidant drug BAI, identified through high-throughput screening of NPL, could optimize the biological function of PPNs; the newly-synthesized BPPNs may accelerate diabetic wound healing through dual mechanisms of promoting angiogenesis and combating oxidative stress.Graphical abstract

Synergistic Antioxidant Activity of Lycium barbarum Polysaccharide and Chlorogenic Acid and Its Effect on Inflammatory Response of NR8383 Cells.

It is inevitable for polyphenols and polysaccharides to interact during food preparation. Modifications in microstructure can lead to changes in the physical and chemical properties of food systems, which in turn may influence the nutritional characteristics and functional activities of the food. Recent studies have shown that, in addition to traditional Chinese medicine compounds, certain natural polysaccharides and polyphenols exhibit significant anti-inflammatory and antioxidant properties. These compounds are also associated with beneficial therapeutic effects for the prevention and treatment of acute lung injury. The objective of this study was to examine the synergistic antioxidant effects of chlorogenic acid (CA) and Lycium barbarum polysaccharide (LBP) in various ratios, along with their combined antioxidant and anti-inflammatory effects on LPS-induced inflammation in rat alveolar macrophages. Using the Combination Index (CI), which quantifies the synergistic or antagonistic effect of two substances, all four combinations showed synergistic antioxidant properties over a range of concentrations by in vitro antioxidant property experiments. However, based on comparing them, the four group ratios exhibited the highest antioxidant activity of the infusion at CA:LBP = 1:7, indicating synergistic interactions (CI < 1). In addition, the antioxidant and anti-inflammatory effects of the CA-LBP complex were observed to alleviate cellular inflammatory injury by reducing LPS-induced nitric oxide and reactive oxygen species production and inhibiting the release of inflammatory factors such as TNF-α and IL-6.

Development, characterization, and assessment of PLAROsomal vesicular system of curcumin for enhanced stability and therapeutic efficacy

BackgroundCurcumin (CUR) is a natural polyphenol and one of the key phytoconstituents found in the rhizomes of Curcuma Longa. It exhibits various pharmacological properties, encompassing antioxidant, anticancer effects, antiseptic, and anti-inflammatory, among several others.A significant drawback of using CUR is its limited bioavailability, which primarily depends on gut microorganisms responsible for converting it into its bioavailable form. Therefore, the contemporary study intended to formulate a novel PLAROsomal vesicular delivery of CUR, i.e., CUR-PLAROsomes employing a design of experiments approach to examine the influence of various process parameters, such as particle size and drug percentage release.ResultThe prepared CUR-PLAROsomes were characterized for their physicochemical properties using various hyphenated tools. The CUR-PLAROsomes exhibited sizes ranging from 40 to 300 nm, and the optimized batch demonstrated a drug entrapment of 86.38 ± 0.22%.In-vitro anticancer studies were conducted using human colorectal adenocarcinoma cells (COLO320DM) and human breast adenocarcinoma (MCF-7). CUR-PLAROsomes exhibited significant in-vivo anti-inflammatory potential against carrageenan-induced paw edema. CUR-PLAROsomes were more potent against COLO320DM and MCF-7 cell lines, even at lower concentrations, than pure CUR.ConclusionFurthermore, based on the observations, it exhibits potential as an anti-inflammatory agent, suggesting that PLAROsomes are an effective vesicular drug delivery system.HighlightsNewly introduced PLARosome is a next generation of Liposomes which have gain popularity owing to its better adaptability to overcome leakage problem of vesicular drug delivery system.This is the pioneer attempt to prepare Curcumin-loaded PLARosome as an anti-cancer and anti-inflammatory activity.Nano size of the PLAROsomes may contribute to enhance the efficacy of Curcumin as a target specific drug delivery system.Site specific delivery of phytoconstituents is possible by use of PLAROsomes as a novel drug delivery system.Graphical abstract

Natural Polyphenol‐Reinforced Ion‐Selective Separators for High‐Performance Lithium‐Sulfur Batteries with High Sulfur Loading and Lean Electrolyte

AbstractIon‐selective separators are promising to inhibit soluble intermediates shuttle in practical lithium‐sulfur (Li−S) batteries. However, designing and fabricating such high‐performance ion‐selective separators using cost‐effective, eco‐friendly, and versatile methods remains a formidable challenge. Here we present ion‐selective separators fabricated via the spontaneous deposition of green tea‐derived polyphenols onto a polypropylene separator, aimed at enhancing the stability of Li−S batteries. The resulting natural polyphenol‐reinforced ion‐selective (NPRIS24) separators exhibit rapid Li ion transport and high soluble intermediates inhibition capability with an ultralow shuttle rate of 0.67 % for Li2S4, 0.19 % for Li2S6 and 0.10 % for Li2S8. This superior ion‐selectivity arises from the high electronegativity and strong lithiophilic nature of the phenolic compounds. Consequently, we have achieved high‐performance Li−S batteries that are steadily cyclable under the challenging conditions of an S loading of 5.7 mg cm−2, an electrolyte‐to‐S ratio of 5.1 μL mg−1, and a 50 μm Li foil anode. Furthermore, the NPRIS24 separator enhances the performance of other Li metal batteries utilizing commercial LiFePO4 (5.3 mg cm−2) and LiNi0.5Co0.2Mn0.3O2 (9.9 mg cm−2) cathodes. This work underscores the potential of utilizing natural polyphenols for the design of advanced ion‐selective separators in energy storage systems.

Natural Polyphenol-Reinforced Ion-Selective Separators for High-Performance Lithium-Sulfur Batteries with High Sulfur Loading and Lean Electrolyte.

Ion-selective separators are promising to inhibit soluble intermediates shuttle in practical lithium-sulfur (Li-S) batteries. However, designing and fabricating such high-performance ion-selective separators using cost-effective, eco-friendly, and versatile methods remains a formidable challenge. Here we present ion-selective separators fabricated via the spontaneous deposition of green tea-derived polyphenols onto a polypropylene separator, aimed at enhancing the stability of Li-S batteries. The resulting natural polyphenol-reinforced ion-selective (NPRIS24) separators exhibit rapid Li ion transport and high soluble intermediates inhibition capability with an ultralow shuttle rate of 0.67 % for Li2S4, 0.19 % for Li2S6 and 0.10 % for Li2S8. This superior ion-selectivity arises from the high electronegativity and strong lithiophilic nature of the phenolic compounds. Consequently, we have achieved high-performance Li-S batteries that are steadily cyclable under the challenging conditions of an S loading of 5.7 mg cm-2, an electrolyte-to-S ratio of 5.1 μL mg-1, and a 50 μm Li foil anode. Furthermore, the NPRIS24 separator enhances the performance of other Li metal batteries utilizing commercial LiFePO4 (5.3 mg cm-2) and LiNi0.5Co0.2Mn0.3O2 (9.9 mg cm-2) cathodes. This work underscores the potential of utilizing natural polyphenols for the design of advanced ion-selective separators in energy storage systems.

Supramolecular nanomedicine targeted therapy for tumor treatment

Abstract. In recent years, the incidence of multiple myeloma (MM) has been increasing significantly and showing a trend of younger age. With the advent of new therapies, the median overall survival of patients with MM has improved, but some still relapse early or even pass away. Meanwhile, chemotherapy drugs such as Bortezomib (BTZ) used in patients bring great pain to them because of its non-targeting. Based on this, this paper explores a supramolecular nanomedicine with targeted therapeutic effect on tumors and evaluates the potential of this drug to form new supramolecular nanomedicine. The drug is a combination of BTZ, the natural polyphenol Caffeic Acid (CA), and iron ion (Fe3+), a supramolecular design that brings many advantages to cancer treatment systems, including efficient drug loading, excellent biodegradability and bio-compatibility. Studies have shown that this supramolecular nanomedicine can effectively reduce the killing effect of chemotherapy BTZ on normal cells. This kind of supramolecular nanomedicine provides a new idea for the construction of tumor targeting drugs and is also hopeful to be applied to more chemotherapy drugs.

Carpet Grass Polyphenol Reductive Degradation of Aqueous Nitrate-A Conceptual Field Application Study.

Rainwater flowing along the ground, and from hard surface such as pavement and roofs, becomes surface water runoff, which flows to surface waters, and infiltrates into the ground to become groundwater. Surface water runoff can contain elevated levels of nitrates (NO3 -) from various sources including animal wastes and fertilizers. Reducing elevated levels of NO3 - in surface water runoff can minimize and/or prevent groundwater and surface water contamination. Natural polyphenols in carpet grass, due to phenolic hydroxyl groups, can degrade aqueous NO3 -. This study evaluated the potential for carpet grass to purify water by denitrifying NO3 - as surface water flows through grass-covered land. The research investigated nitrate removal efficiency and reaction kinetics under various flow rates and doses of carpet grass, validating the feasibility of using natural polyphenols for water purification. A grass dose of 100 g and a retention time of 24 h, which produced approximately 20-80 mg/L as gallic acid equivalent (GAE) of polyphenol in simulated surface water runoff, were demonstrated to effectively degrade NO3 - in aqueous solution (110 mg/L) and result in the denitrification of NO3 - to nitrite (NO2 -) and eventually N2. The first-order reaction kinetic rate constants for NO3 - degradation, NO2 - formation, and subsequent degradation of NO2 - are k obs(NO3-degradation) = 6.89 × 10-2 h-1, k 1(NO2-formation) = 5.11 × 10-2 h-1, and k 2(NO2-degradation) = 4.63 × 10-2 h-1, respectively, with a conversion rate (α) of NO3 - to NO2 - to be 0.74. Implementing natural vegetation, such as carpet grass, in water management practices offers an environmentally sustainable approach to reducing nitrate contamination in surface water runoff.

Curcumin Induces MCF-7 Breast Cancer Cell Apoptosis Through miR-15a Alteration

Background: In recent years, the application of herbal compounds in cancer treatment has shown significant progress. Curcumin (CUR), a natural polyphenol, demonstrates potent anti-cancer effects against various cancers, including breast cancer (BC). Curcumin targets a range of molecular pathways, contributing to the inhibition of cancer cell proliferation, metastasis, and angiogenesis, and promoting apoptosis. Objectives: This study aimed to assess the effect of CUR on BC cells, focusing on alterations in the expression levels of Mir-15a and Bcl-2 through the apoptotic pathway. Methods: The cytotoxicity of CUR was evaluated using an MTT assay. Changes in the expression of Mir-15a and Bcl-2 genes were analyzed by real-time PCR, and cell apoptosis was measured using flow cytometry. Data analysis was conducted using SPSS. Results: The MTT assay results indicated that cell viability decreased as CUR concentration increased (5 – 25 µM). Real-time PCR results showed a significant decrease in the expression of Mir-15a and Bcl-2 (P &lt; 0.05). Flow cytometry findings demonstrated that CUR treatment at the IC50 concentration for 48 hours induced apoptosis in 75.9% of MCF-7 cells. Conclusions: Our study provides a crucial foundation indicating that CUR induces apoptosis in MCF-7 cells by modulating the expression of Mir-15a.

The Metabolic Characteristics and Bioavailability of Resveratrol Based on Metabolic Enzymes.

The natural polyphenol resveratrol (RV) has garnered fame for its extensive pharmacological properties. Although clinical studies have shown some positive results, many contradictory outcomes remain. An important obstacle to the development of therapeutic applications for RV is its low bioavailability in vivo. This may be partially attributed to biotransformation mediated by phase I and II enzymes, such as cytochrome P450s, UDP-glucuronosyltransferases, and sulfotransferases. To date, more than 20 different types of metabolites have been detected after catalysis by these enzymes. Notably, RV and some of its metabolites serve as substrates for these enzymes. Conversely, RV can directly regulate the expression or activity of these enzymes. Given the increasing number of studies investigating the bioactivity of RV, this review summarizes its physicochemical and pharmacokinetic characteristics and describes the metabolism of RV and the bioactivities of its metabolites, with emphasis on the interaction between RV and its related metabolic enzymes. In addition to hepatic metabolism, the crucial roles of RV metabolism in multiple other tissues and organs cannot be overlooked, and they reveal the relationship between RV metabolism and its biological potential.

Curcumin-Etoposide Synergy: Unveiling the Molecular Mechanisms of Enhanced Apoptosis and Chemoresistance Attenuation in Breast Cancer

Background: Combining natural compounds with chemotherapeutic agents has emerged as a promising approach for cancer treatment. Curcumin (Cur), a natural polyphenol, is known for its anti-cancer properties, including the ability to induce apoptosis and arrest cell cycle progression. Objectives: This study aimed to evaluate the effects of Cur and etoposide (ETO), both individually and in combination, on the induction of apoptosis in breast cancer (BC) cell lines. Methods: The impact of Cur and ETO on cell proliferation was assessed using MTT viability assays. Apoptosis induction by these drugs was evaluated through Annexin V flow cytometry and caspase-3 and caspase-9 activity assays. Quantitative real-time PCR was employed to measure Bax and Bcl-2 gene expression levels. Western blotting was conducted to determine protein levels of p53, p21, Bax, and Bcl-2. Results: A non-significant dose of ETO was selected based on MTT assay results and combined with 75 µM of Cur. Curcumin enhanced ETO’s pro-apoptotic effect by increasing caspase activities. The combination of Cur and ETO significantly reduced Bcl-2 gene expression while upregulating Bax expression. Furthermore, treatment with this combination elevated the protein levels of p53, p21, and Bax, compared to ETO or Cur alone, while significantly decreasing Bcl-2 protein levels. Conclusions: Cur has the potential to amplify ETO-induced apoptosis in BC cells. This combination may offer a promising therapeutic approach for BC.

Nanoenabled Self-Assembled Metal-Organic Algaecides Generated Photosynthetic Inhibition and Oxidative Stress for Sustainable Food Security.

Achieving food sustainability is one of the biggest challenges in the new millennium. Plant factory cultivation systems provide an alternative for food sustainability, while they often suffer from algal blooms. The overuse of conventional algaecides has caused significant environmental pollution and concerns about food security. Here, we design a nanoenabled metal-organic algaecide that is self-assembled from natural polyphenols and two functional metal ions for providing shading effects and delivering active ingredients synergistically to suppress algal blooms. Black wattle tannin (BWT) and Fe3+ ions are utilized to develop self-assembled FeBWT nanoalgaecides with significant shading effects for decreasing light transmission (up to 97 %) and effectively inhibiting algal photosynthesis. Further, the FeBWT is functionalized with Cu2+ ions (bimetallic Cu/FeBWT) to target the algal cells and release Cu2+ ions via phenolic-mediated cell surface interactions, thus enhancing the inhibition efficiency. Importantly, the biosafety of Cu/FeBWT is demonstrated through toxicity tests on zebrafish and NIH3T3 cells. In our real-world field test, the Cu/FeBWT demonstrates high algal inhibition performance (>95 %, over 30 days), and enhances the accumulation of food nutrients in model plant lettuces. Collectively, the supramolecular metal-organic nanoalgaecide provides a promise for nanoagrochemical application and promotes food sustainability and security.

Resveratrol Potentiates BCG-induced Trained Immunity in Human Monocytes.

Resveratrol is a natural polyphenol derived from plants such as grapes and berries. In addition to its role in plants during injury and infection, various cardioprotective, neuroprotective, and longevity-promoting effects were reported in diverse model organisms. The primary target of resveratrol is the deacetylase Sirtuin 1 (SIRT1), which regulates many immunological processes, including BCG-induced trained immunity response in humans. We, therefore, investigated the effect of resveratrol on trained immunity induced by BCG, β-glucan, C. albicans, or oxidized low-density lipoprotein (oxLDL). Using an in-vitro model of trained immunity with monocytes obtained from healthy donors, we demonstrate that resveratrol amplifies BCG-induced trained immunity regarding IL-6 and TNFα production after a secondary challenge. Although resveratrol did not improve and even limited glycolysis, oxidative phosphorylation, and reactive oxygen species production, it enhanced the permissive epigenetic mark H3K27Ac on IL-6 and TNFα promoters. In contrast to BCG-induced trained immunity, resveratrol potently inhibited training induced by β-glucan, C. albicans, oxLDL, and muramyl dipeptide (MDP), a peptidoglycan component of BCG. Resveratrol's unique boosting effect on BCG training depended on BCG being alive and metabolically active. These results suggest that resveratrol might amplify the effects of BCG vaccination, which should be mechanistically characterized further. In addition, resveratrol could alleviate oxLDL-induced training of innate immune cells in atherosclerosis, and in-vivo studies of trained immunity combined with resveratrol are warranted to explore these therapeutic possibilities.

Resveratrol Inhibits Nucleosome Binding and Catalytic Activity of PARP1.

The natural polyphenol resveratrol is a biologically active compound that interacts with DNA and affects the activity of some nuclear enzymes. Its effect on the interaction between nucleosomes and poly(ADP-ribose) polymerase-1 (PARP1) and on the catalytic activity of PARP1 was studied using Western blotting, spectrophotometry, electrophoretic mobility shift assay, and single particle Förster resonance energy transfer microscopy. Resveratrol inhibited PARP1 activity at micro- and sub-micromolar concentrations, but the inhibitory effect decreased at higher concentrations due to the aggregation of the polyphenol. The inhibition of PARP1 by resveratrol was accompanied by its binding to the enzyme catalytic center and a subsequent decrease in PARP1 affinity to nucleosomal DNA. Concurrent binding of talazoparib to the substrate binding pocket of PARP1, which occurs in the presence of resveratrol, restores the interaction of PARP1 with nucleosomes, suggesting that the binding sites of resveratrol and talazoparib overlap. The data suggest that resveratrol can be classified as a natural inhibitor of PARP1.