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Interruption of wound healing by multi-drug resistant-bacterial infection is a harmful issue for the worldwide health care system, and conventional treatment approaches may not resolve this issue due to antimicrobial resistance. So, there is an unmet need to develop scaffolds with intrinsic wound healing properties to combat bacterial-infected wounds. Inspired by the α-lactalbumin's (Lalb's) ability to promote collagen synthesis, we herein electrospun Lalb with cephalexin (CPL) and epigallocatechin (EP) to produce nanofibers (CE-Lalb NFs) to solve this issue. The CE-Lalb NFs were prepared using the electrospinning technique and subjected to physicochemical characterizations, in vitro, and in vivo assessments. The CE-Lalb NFs promoted fibroblast migration, proliferation, and collagen synthesis, while CPL/EP annihilated MRSA and E. coli infections. Physicochemical characterizations proved the successful fabrication and doping of CE-Lalb NFs. Antimicrobial assays and fractional inhibitory concentration index (FICI) declared synergistic antibacterial activity of CE-Lalb NFs against MRSA and E. coli. The in vivo and immunohistochemical data evidenced its exceptional potential for wound healing, promoting growth factor, collagen synthesis, and reduced scar formation. The presence of mature collagen, fewer inflammatory cytokines, increased expression of blood vessels, and low expression of IL-6 at the wound site support in vitro and in vivo results. In our view, the tailored scaffold is the next step for personalized wound dressings that could meet patients with infected wounds' unmet needs by the subscription of noninvasive and easily navigable therapeutic options., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Natural polyphenols are promising alternatives to antifungals for novel treatments of vulvovaginal candidiasis (VVC) in an era of antimicrobial resistance. However, polyphenols are poorly soluble and prone to degradation. To overcome their limitations, we propose incorporation in liposomes. The study aimed to develop chitosan and liposome comprising delivery systems for epicatechin (EC) or propyl gallate (PG) as treatment of VVC. EC was selected for its antioxidative properties and PG as an ester of antifungal gallic acid. To improve formulation retention at vaginal site, mucoadhesive chitosan was introduced into formulation as liposomal surface coating or hydrogel due to intrinsic antifungal properties. These polyphenol-loaded liposomes exhibited an average size of 125 nm with a 64 % entrapment efficiency (for both polyphenols). A sustained in vitro polyphenol release was seen from liposomes, particularly in chitosan hydrogel (p < 0.01 or lower). Viscosity was evaluated since increased viscosity upon mucin contact indicated adhesive bond formation between chitosan and mucin confirming mucoadhesiveness of formulations. Antifungal activity was evaluated by the broth microdilution method on Candida albicans CRM-10231. Unlike PG, incorporation of EC in liposomes enabled antifungal activity. Fungicidal activity of chitosan was confirmed both when used as liposomal coating material and as hydrogel vehicle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study examined the suppressive effects of 16 selected plant-based foods on α-glucosidase and pancreatic lipase and their antioxidant properties. Among these, the bark of Cinnamomum cassia (Cinnamon, WLN-FM 15) showed the highest inhibitory activity against α-glucosidase and the highest antioxidant activity. Additionally, WLN-FM 15 showed promising results in the other tests. To further identify the bioactive constituents of WLN-FM 15, a multi-bioactivity-labeled molecular networking approach was used through a combination of GNPS-based molecular networking, DPPH-HPLC, and affinity-based ultrafiltration-HPLC. A total of nine procyanidins were identified as antioxidants and inhibitors of α-glucosidase and pancreatic lipase in WLN-FM 15. Subsequently, procyanidins A1, A2, B1, and C1 were isolated, and their efficacy was confirmed through functional assays. In summary, WLN-FM 15 has the potential to serve as a functional food ingredient with the procyanidins as its bioactive constituents. These results also suggest that the multi-bioactivity-labeled molecular networking approach is reliable for identifying bioactive constituents in plant-based foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Modulation of immune microenvironment is critical for inflammatory bowel disease (IBD) intervention. Epigallocatechin gallate (EGCG), as a natural low toxicity product, has shown promise in treating IBD. However, whether and how EGCG regulates the intestinal microenvironment is not fully understood. Here we report that EGCG lessens colitis by orchestrating Th1 polarization and self-amplification in a novel manner that required multilevel-regulated intestinal microecosystem. Mechanistically, EGCG activates GPR43 on IEC to inhibit Th1 polarization dependently of short chain fatty acid (SCFA)-producing gut microbiota. Inhibition of GPR43 activity weakens the protective effects of EGCG on colitis development. Moreover, we confirm that fecal SCFAs and/or intestinal GPR43 are limited in patients with colitis and are correlated with Th1 cell number. Taken together, our study reveals an intestinal microenvironment-dependent immunoregulatory effects of EGCG in treating IBD and provides insight into mechanisms of EGCG-based novel immunotherapeutic strategies for IBD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The study aimed to examine effects of (-)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Natural antioxidants have become the subject of many investigations due to the role that they play in the reduction of oxidative stress. Their main scavenging mechanisms concern the direct inactivation of free radicals and the coordination of metal ions involved in Fenton-like reactions. Recently, increasing attention has been paid to non-covalent inhibition of enzymes involved in different diseases by the antioxidants. Here, a computational investigation on the primary antioxidant power of (+)-catechin against the • OOH radical has been performed in both lipid-like and aqueous environments, taking into account the relevant species present in the simulated acid-base equilibria at the physiological pH. Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET), and Radical Adduct Formation (RAF) mechanisms were studied, and relative rate constants were estimated. The potential inhibitory activity of the (+)-catechin towards the most important proteases from SARS-CoV-2, 3C-like (M pro ) and papain-like (PL pro ) proteases was also investigated by MD simulations to provide deeper atomistic insights on the binding sites. Based on the antioxidant and antiviral properties also unravelled by comparison with other molecules having similar chemical scaffold, our results propose that (+)-CTc satisfies can explicate a dual action as antioxidant and antiviral in particular versus M pro from SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diet is of major importance in modulating intestinal inflammation, as the gastrointestinal tract is directly exposed to high concentrations of dietary components. Procyanidins are flavan-3-ol oligomers abundant in fruits and vegetables. Although with limited or no intestinal absorption, they can have GI health benefits which can promote overall health. We previously observed that epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) dimers inhibit in vitro colorectal cancer cell proliferation and invasiveness. Inflammation-mediated intestinal barrier permeabilization can result in a chronic inflammatory condition and promote colorectal cancer onset/progression. Thus, this study investigated the structure-dependent capacity of ECG, EGCG and (-)-epicatechin (EC) dimers to inhibit tumor necrosis factor alpha (TNFα)-induced inflammation, oxidative stress, and loss of barrier integrity in Caco-2 cells differentiated into an intestinal epithelial cell monolayer. Cells were incubated with TNFα (10 ng/ml), in the absence/presence of ECG, EGCG and EC dimers. The three dimers inhibited TNFα-mediated Caco-2 cell monolayer permeabilization, modulating events involved in the loss of barrier function and inflammation, i.e. decreased tight junction protein levels; increased matrix metalloproteinases expression and activity; increased NADPH oxidase expression and oxidant production; activation of the NF-κB and ERK1/2 pathways and downstream events leading to tight junction opening. For some of these mechanisms, the galloylated ECG and EGCG dimers had stronger protective potency than the non-galloylated EC dimer. These differences could be due to differential membrane interactions as pointed out by molecular dynamics simulation of procyanidin dimers-cell membrane interactions and/or by differential interactions with NOX1. Results show that dimeric procyanidins, although poorly absorbed, can promote health by alleviating intestinal inflammation, oxidative stress and barrier permeabilization., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Brain Muscle ARNT-Like Protein 1 (BMAL1) suppresses oxidative stress in brain injury during surgery. Epigallocatechin-3-gallate (EGCG), a monomer in green tea, has been identified as an antioxidant and a potential agonist for BMAL1. In this work, the mechanism by which BMAL1 is regulated was investigated, as well as the therapeutic effect of EGCG on surgically injured rats. The pathological environment after brain injury during surgery was simulated by excising the right frontal lobe of rats. Rats received an intraperitoneal injection of EGCG immediately after surgery. Neurological scores and cerebral edema were recorded after surgery. Fluoro-Jade C staining, TUNEL staining, western blot, and lipid peroxidation analyses were conducted 3 days later. Here we show that the endogenous BMAL1 level decreased after brain injury. Postoperative administration of EGCG up-regulated the content of BMAL1 around the cerebral cortex, reduced the oxidative stress level, reduced neuronal apoptosis and the number of degenerated neurons, alleviated cerebral edema, and improved neurological scores in rats. This suggests that BMAL1 is an effective target for treating surgical brain injury, as well as that EGCG may be a promising agent for alleviating postoperative brain injury., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Theabrownin (TB) is a dark brown pigment from Pu-erh tea or other dark teas. It is formed by further oxidization of theaflavins and thearubigins, in combination with proteins, polysaccharides, and caffeine etc. TB is a characteristic ingredient and bioactive substance of Pu-erh tea. However, the effects of TB on ulcerative colitis (UC) remains unclear., Purpose: This study aims to elucidate the mechanism of TB on UC in terms of recovery of intestinal homeostasis and regulation of toll-like receptor (TLR) 2&4 signaling pathway., Methods: The colitis models were established by administering 5% dextran sulfate sodium (DSS) to C57BL/6 mice for 5 days to evaluate the therapeutic and preventive effects of TB on UC. Mesalazine was used as a positive control. H&E staining, complete blood count, enzyme-linked immunosorbent assay, immunohistochemistry, flow cytometry, and 16S rRNA sequencing were employed to assess histological changes, blood cells analysis, content of cytokines, expression and distribution of mucin (MUC)2 and TLR2&4, differentiation of CD4 + T cells in lamina propria, and changes in intestinal microbiota, respectively. Western blot was utilized to study the relative expression of tight junction proteins and the key proteins in TLR2&4-mediated MyD88-dependent MAPK, NF-κB, and AKT signaling pathways., Results: TB outstanding alleviated colitis, inhibited the release of pro-inflammatory cytokines, reduced white blood cells while increasing red blood cells, hemoglobin, and platelets. TB increased the expression of occludin, claudin-1 and MUC2, effectively restored intestinal barrier function. TB also suppressed differentiation of Th1 and Th17 cells in the colon's lamina propria, increased the fraction of Treg cells, and promoted the balance of Treg/Th17 to tilt towards Tregs. Moreover, TB increased the Firmicutes to Bacteroides (F/B) ratio, as well as the abundance of Akkermansia, Muribaculaceae, and Eubacterium&#95;coprostanoligenes&#95;group at the genus level. In addition, TB inhibited the activation of TLR2&4-mediated MAPK, NF-κB, and AKT signaling pathways in intestinal epithelial cells of DSS-induced mice., Conclusion: TB acts in restoring intestinal homeostasis and anti-inflammatory in DSS-induced UC, and exhibiting a preventive effect after long-term use. In a word, TB is a promising beverage, health product and food additive for UC., Competing Interests: Declaration of competing interest The authors declare that they have no known conflict of interest or individual connections that could have appeared to impact the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Catechin is a kind of flavonoids, mainly derived from the plant Camellia sinensis. It has a strong antioxidant effect, and it also has significant therapeutic effects on anti-cancer, anti-diabetes, and anti-infection. This study was intended to look at how catechin affected the malignant biological activity of gastric cancer cells. We used databases to predict the targets of catechin and the pathogenic targets of gastric cancer. Venn diagram was used to find the intersection genes, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed on intersection genes. Using the STRING database, the Protein-Protein Interaction (PPI) network was built. The top 8 genes were screened by Cytoscape 3.9.1, then their binding was verified by molecular docking. The proliferation ability, cell cycle, apoptosis and migration of gastric cancer cells were detected, as well as the protein expression levels of PI3K, p-AKT, and AKT and the mRNA expression levels of AKT1, VEGFA, EGFR, HRAS, and HSP90AA1 in gastric cancer cells. Our research revealed that different concentrations of catechin could effectively inhibit the proliferation and migration of gastric cancer cells, regulate the cell cycle, and promote the death of these cells, and it's possible that the PI3K/Akt pathway was crucial in mediating this impact. Moreover, adding the PI3K/Akt pathway agonist significantly reduced the promoting effect of catechin on the apoptosis of gastric cancer cells. This study suggested that catechin was a potential drug for the treatment of gastric cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

(-)-Epicatechin gallate (ECG) is beneficial to the treatment of cardiovascular diseases (CVDs), especially atherosclerosis (AS) through antioxidant stress, but there is a lack of detailed mechanism research. In this study, the therapeutic target of ECG was determined by crossing the drug target and disease target of CVDs and AS. The combination ability of ECG with important targets was verified by Discovery Studio software. The abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by Ang-II and the oxidative damage of AML 12 induced by H 2 O 2 were established to verify the reliability of ECG intervention on the target protein. A total of 120 ECG targets for the treatment of CVDs-AS were predicted by network pharmacology. The results of molecular docking showed that ECG has strong binding force with VEGFA, MMP-9, CASP3 and MMP-2 domains. In vitro experiments confirmed that ECG significantly reduced the expression of VEGFA, MMP-9, CASP3 and MMP-2 in Ang-II-induced VSMCs, and also blocked the abnormal proliferation, oxidative stress and inflammatory reaction of VSMCs by inhibiting the phosphorylation of PI3K signaling pathway. At the same time, ECG also interfered with H 2 O 2 -induced oxidative damage of AML 12 cells, decreased the expression of ROS and MDA and cell foaming, and increased the activities of antioxidant enzymes such as SOD, thus playing a protective role., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

2. This research investigates the impact of the EGCG-CSH/n-HA/CMC composite material on bone defect repair, emphasizing its influence on macrophage polarization and osteogenic differentiation of BMSCs. Comprehensive evaluations of the composite's physical and chemical characteristics were performed. BMSC response to the material was tested in vitro for proliferation, migration, and osteogenic potential. An SD rat model was employed for in vivo assessments of bone repair efficacy. Both transcriptional and proteomic analyses were utilized to delineate the mechanisms influencing macrophage behavior and stem cell differentiation. The material maintained excellent structural integrity and significantly promoted BMSC functions critical to bone healing. In vivo results confirmed accelerated bone repair, and molecular analysis highlighted the role of macrophage M2 polarization, particularly through changes in the SIRPA gene and protein expression. EGCG-CSH/n-HA/CMC plays a significant role in enhancing bone repair, with implications for macrophage and BMSC function. Our findings suggest that targeting SIRPA may offer new therapeutic opportunities for bone regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Notch signaling is a key molecular pathway that regulates cell fate and development. Aberrant Notch signaling can lead to carcinogenesis and progression of malignant tumors. However, current therapies targeting Notch pathway lack specificity and induce high toxicity. In this report, a tumor microenvironment-responsive and injectable hydrogel is designed to load plasmid DNA complexes as a cascade gene delivery system to achieve precise Notch-targeted gene therapy of colorectal cancer (CRC). The hydrogels are prepared through cross-linking between phenylboric acid groups containing poly(oligo(ethylene glycol)methacrylate) (POEGMA) and epigallocatechin gallate (EGCG), used to load the complexes between plasmid DNA encoding short hairpin RNAs of Notch1 (shNotch1) and fluorinated polyamidoamine (PAMAM-F) (PAMAM-F/shNotch1). In response to low pH and H 2 O 2 in tumor microenvironment, the hydrogel can be dissociated and release the complexes for precise delivery of shNotch1 into tumor cells and inhibit Notch1 activity to suppress malignant biological behaviors of CRC. In the subcutaneous tumor model of CRC, PAMAM-F/shNotch1-loaded hydrogels can accurately attenuate Notch1 activity and significantly inhibit tumor growth without affecting Notch signal in adjacent normal tissues. Therefore, this therapeutic system can precisely inhibit Notch1 signal in CRC with high responsiveness and low toxicity, providing a promising Notch-targeted gene therapeutic for human malignancy., (© 2024 Wiley‐VCH GmbH.)

The widespread use of chlorine-based disinfectants in drinking water treatment has led to the proliferation of chlorine-resistant bacteria and the risk of disinfection byproducts (DBPs), posing a serious threat to public health. This study aims to explore the effectiveness and potential applications of epigallocatechin gallate (EGCG) against chlorine-resistant Bacillus and its spores in water, providing new insights for the control of chlorine-resistant bacteria and improving the biological stability of distribution systems. The inactivation effects of EGCG on Bacillus subtilis (B. subtilis) and its spores were investigated using transmission electron microscopy, ATP measurement, and transcriptome sequencing analysis to determine changes in surface structure, energy metabolism, and gene expression levels, thereby elucidating the inactivation mechanism. The results demonstrate the potential application of EGCG in continuously inhibiting chlorine-resistant B. subtilis in water, effectively improving the biological stability of the distribution system. However, EGCG is not suitable for treating raw water with high spore content and is more suitable as a supplementary disinfectant for processes with strong spore removal capabilities, such as ozone, ultraviolet, or ultrafiltration. EGCG exhibits a disruptive effect on the morphological structure and energy metabolism of B. subtilis and suppresses the synthesis of substances, energy metabolism, and normal operation of the antioxidant system by inhibiting the expression of multiple genes, thereby achieving the inactivation of B. subtilis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bone and tooth defects can considerably affect the quality of life and health of patients, and orthopedic implants remain the primary method of addressing such defects. However, implant materials cannot coordinate with the immune microenvironment because of their biological inertness, which may lead to implant loosening or failure. Motivated by the microstructure of nacre, we engineered a biomimetic micro/nanoscale topography on a tantalum surface using a straightforward method. This comprised an organized array of tantalum nanotubes arranged in a brick wall structure, with epigallocatechin gallate acting as "mortar." The coating improved the corrosion resistance, biocompatibility, and antioxidant properties. In vitro and in vivo evaluations further confirmed that coatings can create a favorable bone immune microenvironment through the synergistic effects of mechanochemistry and enhance bone integration. This research offers a new viewpoint on the creation of sophisticated functional implants, possessing vast potential for use in the regeneration and repair of bone tissue.

An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'- O -gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis. Furthermore, the protective effect of B2-3'-G against alcohol-induced liver injury (ALI) was investigated. Compared with the parent compounds, B2-3'-G exhibited a stronger capacity for inhibiting ALI, attributed to its polymerization degree and galloyl group. Subsequent experiments revealed that the pretreatment of BRL-3A cells with B2-3'-G prior to ethanol improved ALI through activation of the Nrf2-HO-1/NQO1 pathway and initiation of enzymatic antioxidant systems. These findings suggest that GPC B2-3'-G is a potential hepatoprotective agent, which provides a new perspective for functional development of GPCs.

Fluoride is a double-edged sword. It was widely used for early caries prevention while excessive intake caused a toxicology effect, affected enamel development, and resulted in dental fluorosis. The study aimed to evaluate the protective effect and mechanism of Epigallocatechin-3-gallate (EGCG) on the apoptosis induced by fluoride in ameloblast-like cells. We observed that NaF triggered apoptotic alterations in cell morphology, excessive NaF arrested cell cycle at the G1, and induced apoptosis by up-regulating Bax and down-regulating Bcl-2. NaF activated the insulin-like growth factor receptor (IGFR), and phosphatidylinositol-3-hydroxylase (p-PI3K), while dose-dependently down-regulating the expression of Forkhead box O1 (FoxO1). EGCG supplements reversed the changes in LS8 morphology, the cell cycle, and apoptosis induced by fluoride. These results indicated that EGCG possesses a protective effect against fluoride toxicity. Furthermore, EGCG suppressed the activation of p-PI3K and the down-regulation of FoxO1 caused by fluoride. Collectively, our findings suggested that EGCG attenuated fluoride-induced apoptosis by inhibiting the PI3K/FoxO1 signaling pathway. EGCG may serve as a new alternative method for dental fluorosis prevention, control, and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Developing multifunctional films with antibacterial, antioxidant, and sustained-release properties is a robust strategy for preventing contamination of perishable fruits by foodborne microorganisms. This study engineered a sustained-release biodegradable antibacterial film loaded with EGCG (Pickering emulsion (PE)/α-Cyclodextrin (α-CD)/Konjac glucomannan (KGM)) through multi-strategy cross-linking for fruit preservation. EGCG is stabilized using PE and incorporated into the α-CD/KGM inclusion compound; the unique structure of α-CD enhances EGCG encapsulation, while KGM provides the film toughness and surface adhesion. The composite film's physicochemical properties, antioxidant, bacteriostatic and biodegradability were studied. Results showed that Pickering emulsions with 3 % oil phase exhibited excellent stability. Moreover, α-CD introduction increased the loading and sustained release of EGCG from the film, and its concentration significantly affected the light transmission, thermal stability, mechanical strength, mechanical characteristics and antioxidant capacity of the composite membrane. Antioxidant and antimicrobial activities of the composite film increased significantly with increasing α-CD concentration. Application of the film to tomatoes and strawberries effectively inhibited Escherichia coli and Staphylococcus aureus growth, prolonging the shelf-life of the fruits. Notably, the composite film exhibits superior biodegradability in soil. This EGCG-loaded PE/α-CD/KGM composite film is anticipated to be a multifunctional antimicrobial preservation material with sustained-release properties and biodegradable for perishable food applications., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Apostichopus japonicus (A. japonicus) has rich nutritional value and is an important economic crop. Due to its rich endogenous enzyme system, fresh A. japonicus is prone to autolysis during market circulation and storage, resulting in economic losses. In order to alleviate this phenomenon, we investigated the effect of polyphenol oxidase (PPO) mediated (-)-epigallocatechin gallate (EGCG) on the activity and structure of endogenous cathepsin series protein (CEP) from A. japonicus. Research on cathepsin activity showed that PPO mediated EGCG could significantly reduce enzyme activity, resulting in a decrease in enzymatic reaction rate. SDS-PAGE and scanning electron microscopy results showed that PPO mediates EGCG could induce CEP aggregation to form protein aggregates. Various spectral results indicated that EGCG caused changes in the structure of CEP. Meanwhile, the conjugates formed by PPO mediated EGCG had lower thermal stability. In conclusion, PPO mediated EGCG was an effective method to inhibit the endogenous enzyme activity., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although minimally invasive interventional occluders can effectively seal heart defect tissue, they still have some limitations, including poor endothelial healing, intense inflammatory response, and thrombosis formation. Herein, a polyphenol-reinforced medicine/peptide glycocalyx-like coating was prepared on cardiac occluders. A coating consisting of carboxylated chitosan, epigallocatechin-3-gallate (EGCG), tanshinone IIA sulfonic sodium (TSS), and hyaluronic acid grafted with 3-aminophenylboronic acid was prepared. Subsequently, the mercaptopropionic acid-GGGGG-Arg-Glu-Asp-Val peptide was grafted by the thiol-ene "click" reaction. The coating showed good hydrophilicity and free radical-scavenging ability and could release EGCG-TSS. The results of biological experiments suggested that the coating could reduce thrombosis by promoting endothelialization, and promote myocardial repair by regulating the inflammatory response. The functions of regulating cardiomyocyte apoptosis and metabolism were confirmed, and the inflammatory regulatory functions of the coating were mainly dependent on the NF-kappa B and TNF signaling pathway.

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O 2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG's role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier's intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy., (© 2024. The Author(s).)

Background and Purpose: Radiation therapy is a crucial treatment for nonsmall cell lung cancer (NSCLC), but its effectiveness is limited by the resistance of tumor cells to radiation. This study aimed to evaluate the effect of epicatechin (EC) on radiosensitivity in NSCLC and to determine its relationships with matrix metalloproteinase (MMP)-9., Methods: MMP-9 expression was detected by Western blotting, and the expression of the DNA damage marker protein was detected by immunofluorescence. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated using the clonogenesis assay. Flow cytometry was used to determine the cell apoptosis, whereas cell migration and invasion were detected using the transwell assays. The cells were treated with ionizing radiation (IR) and EC to verify the sensitizing effect of EC on radiation therapy., Results: MMP-9 expression was elevated in the NSCLC cells and tissues. DNA damage and cell apoptosis were increased, whereas cell vigor, proliferation, migration, and invasion were significantly decreased after IR. MMP-9 knockdown strengthened the impact of IR on the biological behaviors of the cells. EC + IR had the best effect on promoting DNA damage and the biological behaviors of the NSCLC cells; alternatively, the overexpression of MMP-9 weakened the role of EC., Conclusions: This study shows that EC can downregulate MMP-9 expression, promote DNA damage, reduce cell viability, proliferation, migration, and invasion, and facilitate cell apoptosis, thus, showing potential as a radiosensitizer for NSCLC., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Introduction: Uterine fibroids, the most common nonmalignant tumors affecting the female genital tract, are a significant medical challenge. This article focuses on the most recent studies that attempted to identify novel non-hormonal therapeutic targets and strategies in UF therapy., Areas Covered: This review covers the analysis of the pharmacological and biological mechanisms of the action of natural substances and the role of the microbiome in reference to UFs. This study aimed to determine the potential role of these compounds in UF prevention and therapy., Expert Opinion: While there are numerous approaches for treating UFs, available drug therapies for disease control have not been optimized yet. This review highlights the biological potential of vitamin D, EGCG and other natural compounds, as well as the microbiome, as promising alternatives in UF management and prevention. Although these substances have been quite well analyzed in this area, we still recommend conducting further studies, particularly randomized ones, in the field of therapy with these compounds or probiotics. Alternatively, as the quality of data continues to improve, we propose the consideration of their integration into clinical practice, in alignment with the patient's preferences and consent.

The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1β. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats., (© 2024 Wiley Periodicals LLC.)

Hyaluronic acid (HA) serves as a vitreous substitute owing to its ability to mimic the physical functions of native vitreous humor. However, pure HA hydrogels alone do not provide sufficient protection against potential inflammatory risks following vitrectomy. In this study, HA was crosslinked with 1,4-butanediol diglycidyl ether (BDDE) to form HA hydrogels (HB). Subsequently, the anti-inflammatory agent epigallocatechin gallate (EGCG) was added to the hydrogel (HBE) for ophthalmic applications as a vitreous substitute. The characterization results indicated the successful preparation of HB with transparency, refractive index, and osmolality similar to those of native vitreous humor, and with good injectability. The anti-inflammatory ability of HBE was also confirmed by the reduced expression of inflammatory genes in retinal pigment epithelial cells treated with HBE compared with those treated with HB. In a New Zealand white rabbit model undergoing vitreous substitution treatment, HBE 50 (EGCG 50 μM addition) exhibited positive results at 28 days post-surgery. These outcomes included restored intraocular pressure, improved electroretinogram responses, minimal increase in corneal thickness, and no inflammation during histological examination. This study demonstrated the potential of an injectable HA-BDDE cross-linked hydrogel containing EGCG as a vitreous substitute for vitrectomy applications, offering prolonged degradation time and anti-inflammatory effects postoperatively., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

SARS-CoV-2 main protease (Mpro) is a well-recognized target for COVID-19 therapy. Green tea (-)-epigallocatechin-3-gallate (EGCG) possesses Mpro-inhibitory activity; however, the influence of EGCG oxidation on its inhibition activity remains obscure, given its high oxidation propensity. This study reveals that prolonged EGCG oxidation in the presence of Mpro dramatically increases its inhibitory activity with an IC 50 of 0.26 μM. The inhibitory mechanism is that EGCG-quinone preferentially binds the active site Mpro-Cys145-SH, which forms a quinoprotein. Though Mpro is present in the cell lysate, EGCG preferentially depletes its thiols. Non-cytotoxic EGCG effectively generates a quinoprotein in living cells, thus EGCG might selectively inhibit Mpro in SARS-CoV-2 infected cells. Chlorogenic acid facilitates EGCG oxidation. Together, they synergistically deplete multiple Mpro thiols though this is not more beneficial than EGCG alone. By contrast, excessive EGCG oxidation prior to incubation with Mpro largely compromises its inhibitory activity. Overall, the low IC 50 and the high selectivity imply that EGCG is a promising dietary Mpro inhibitor. While EGCG oxidation in the presence of Mpro has a pivotal role in inhibition, enhancing EGCG oxidation by chlorogenic acid no longer increases its inhibitory potential. EGCG oxidation in the absence of Mpro should be avoided to maximize its Mpro-inhibitory activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The thymus, a site to culture the naïve T lymphocytes, is susceptible to atrophy or involution due to aging, inflammation, and oxidation. Epigallocatechin-3-gallate (EGCG) has been proven to possess anti-inflammatory, antioxidant, and antitumor activity. Here, we investigate the effects of EGCG on thymic involution induced by lipopolysaccharide (LPS), an endotoxin derived from Gram-negative bacteria. The methodology included an in vivo experiment on female Kunming mice exposed to LPS and EGCG. Morphological assessment of thymic involution, immunohistochemical detection, and thymocyte subsets analysis by flow cytometry were further carried out to evaluate the potential role of EGCG on the thymus. As a result, we found that EGCG alleviated LPS-induced thymic atrophy, increased mitochondrial membrane potential and superoxide dismutase levels, and decreased malondialdehyde and reactive oxygen species levels. In addition, EGCG pre-supplement restored the ratio of thymocyte subsets, the expression of autoimmune regulator, sex-determining region Y-box 2, and Nanog homebox, and reduced the number of senescent cells and collagen fiber deposition. Western blotting results indicated that EGCG treatment elevated LPS-induced decrease in pAMPK, Sirt1 protein expression. Collectively, EGCG relieved thymus architecture and function damaged by LPS via regulation of AMPK/Sirt1 signaling pathway. Our findings may provide a new strategy on protection of thymus from involution caused by LPS by using EGCG. And EGCG might be considered as a potential agent for the prevention and treatment of thymic involution., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Introduction: There have been reports on the effects of epigallocatechin gallate (EGCG) against Streptococcus mutans viability and acidogenesis. However, the effects of EGCG on the virulence of S. mutans biofilm development have yet to be fully investigated using validated cariogenic biofilm models., Objective: Thus, this study aimed to evaluate the effects of EGCG on S. mutans biofilm virulence using a validated cariogenic model and clinically relevant treatment regimens, twice a day for 1.5 min., Methods: Effects of EGCG on bacterial viability, polyssacharide synthesis and biofilm acidogenesis were evaluated. The morphology and 3D structure of the biofilms were evaluated by scanning electron (SEM) and confocal laser scanning microscopy, respectively., Results: No significant change in S. mutans viability or culture medium pH were observed when comparing EGCG-treated and NaCl-treated biofilms. EGCG significantly reduced the accumulation of soluble and insoluble polysaccharides, resulting in the formation of a biofilm with interspaced exopolysaccharide-microcolony complexes unevenly distributed on enamel. The SEM images of the biofilm treated with EGCG depict multilayers of cells arranged in short chains of microorganisms adhered to an unstructured matrix, which is not continuous and does not enmesh or protect the microorganisms entirely. Importantly, confocal images demonstrated that treatment with EGCG affected the 3D structure and organization of S. mutans biofilm, which presented a biofilm matrix more confined to the location of the microcolonies., Conclusion: In conclusion, EGCG lowered the virulence of S. mutans matrix-rich biofilm by reducing the synthesis of biofilm matrix components, altering the biofilm matrix structure, organization, and distribution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Walnut isolate protein (WPI)-epigallocatechin gallate (EGCG) conjugates can be employed to creat food-grade delivery systems for preserving bioactive compounds. In this study, WPI-EGCG nanoparticles (WENPs) were developed for encapsulating lycopene (LYC) using the ultrasound-assisted method. The results indicated successful loading of LYC into these WENPs, forming the WENPs/LYC (cylinder with 200-300 nm in length and 14.81-30.05 nm in diameter). Encapsulating LYC in WENPs led to a notable decrease in release rate and improved stability in terms of thermal, ultraviolet (UV), and storage conditions compared to free LYC. Simultaneously, WENPs/LYC exhibited a synergistic and significantly higher antioxidant activity with an EC 50 value of 23.98 μg/mL in HepG2 cells compared to free LYC's 31.54 μg/mL. Treatment with WENPs/LYC led to a dose-dependent restoration of intracellular antioxidant enzyme activities (SOD, CAT, and GSH-Px) and inhibition of intracellular malondialdehyde (MDA) formation. Furthermore, transcriptome analysis indicated that enrichment in glutathione metabolism and peroxisome processes following WENPs/LYC addition. Quantitative real-time reverse transcription PCR (qRT-PCR) verified the expression levels of related genes involved in the antioxidant resistance pathway of WENPs/LYC on AAPH-induced oxidative stress. This study offers novel perspectives into the antioxidant resistance pathway of WENPs/LYC, holding significant potential in food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Obesity and Type 2 diabetes are prevalent metabolic dysfunctions that present significant health challenges worldwide. Available cures for these ailments have constraints with accompanying unwanted effects that persistently exist. Compounds originated from plants have recently been introduced as hopeful remedies to treat metabolic disorders because of their diverse pharmacological activities. This detailed observation gives an introduction into the treatment capacity of plant-derived compounds regarding metabolic syndromes while analyzing various groups alongside their performance in this field despite unique mechanisms designed by nature itself. Interestingly, this study provides some examples including curcumin, resveratrol, quercetin, berberine, epigallocatechin gallate (EGCG), and capsaicin, which highlights potential therapeutic impacts for future testing. However, current clinical trials inspecting human studies investigating efficacies concerning metabolism challenge present limitations. Finally, the review weighs up bad reactions possibly inflicted after administering plant-originated materials though suggestive insights will be provided later. Above all, it outlines the chance to identify novel therapies encapsulated within natural substances based upon recent developments could hold significant promise toward managing misplaced metabolisms globally., (© 2024 John Wiley & Sons Ltd.)

Nanotechnology offers promising avenues for enhancing drug delivery systems, particularly in HIV-1 treatment. This study investigates a nanoemulsified formulation combining epigallocatechin gallate (EGCG) with dolutegravir (DTG) for managing HIV-1 infection. The combinatorial interaction between EGCG and DTG was explored through cellular, enzymatic, and molecular studies. In vitro assays demonstrated the potential of a dual drug-loaded nanoemulsion, NE-DTG-EGCG, in inhibiting HIV-1 replication, with EGCG serving as a supplementary treatment containing DTG. In silico molecular interaction studies highlighted EGCG's multifaceted inhibitory potential against HIV-1 integrase and reverse transcriptase enzymes. Further investigations are needed to validate the formulation's efficacy across diverse contexts. Overall, by integrating nanotechnology into drug delivery systems, this study represents a significant advancement in managing HIV-1 infection., (© 2024 Federation of European Biochemical Societies.)

At present, consumers increasingly favored the natural food preservatives with fewer side-effects on health. The green tea catechins and black tea theaflavins attracted considerable interest, and their antibacterial effects were extensively reported in the literature. Epicatechin (EC), a green tea catechin without a gallate moiety, showed no bactericidal activity, whereas the theaflavin (TF), also lacking a gallate moiety, exhibited potent bactericidal activity, and the antibacterial effects of green tea catechins and black tea theaflavins were closely correlated with their abilities to disrupt the bacterial cell membrane. In our present study, the mechanisms of membrane interaction modes and behaviors of TF and EC were explored by molecular dynamics simulations. It was demonstrated that TF exhibited markedly stronger affinity for the POPG bilayer compared to EC. Additionally, the hydrophobic interactions of tropolone/catechol rings with the acyl chain part could significantly contribute to the penetration of TF into the POPG bilayer. It was also found that the resorcinol/pyran rings were the key functional groups in TF for forming hydrogen bonds with the POPG bilayer. We believed that the findings from our current study could offer useful insights to better understand the stronger antibacterial effects of TF compared to EC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enterococcus faecalis, an opportunistic pathogen responsible for nosocomial infections, exhibits increased pathogenicity via biofilm formation. Theaflavin-3,3'-digallate (TF3), a theaflavin extracted from black tea, exhibits potent antibacterial effects. In the present study, we investigated the inhibitory effect of TF3 on E. faecalis. Our results indicated that TF3 significantly inhibited E. faecalis ATCC 29212 biofilm formation. This observation was further confirmed via crystal violet staining, confocal laser scanning microscopy, and field emission-scanning electron microscopy. To disclose the underlying mechanisms, RNA-seq was applied. TF3 treatment significantly altered the transcriptomic profile of E. faecalis, as evidenced by identification of 248 differentially expressed genes (DEGs). Through functional annotation of these DEGs, several quorum-sensing pathways were found to be suppressed in TF3-treated cultures. Further, gene expression verification via real-time PCR confirmed the downregulation of gelE, sprE, and secY by TF3. These findings highlighted the ability of TF3 to impede E. faecalis biofilm formation, suggesting a novel preventive strategy against E. faecalis infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hemoglobin (Hb) is effective inducer for lipid oxidation and protein-polyphenol interaction is a well-known phenomenon. The effects of the interaction of (-)-epigallocatechin gallate (EGCG) with Hb on lipid oxidation were rarely elucidated. The detailed interaction between bovine Hb and EGCG was systematically explored by experimental and theoretical approaches, to illustrate the molecular mechanisms by which EGCG influenced the redox states and stability of Hb. EGCG would bind to the central pocket of protein with one binding site to form Hb-EGCG complex. The binding constant for Hb-EGCG complex was 0.34 × 10 4  M -1 at 277 K, and thermodynamic parameters (ΔH > 0, ΔS > 0 and ΔG < 0) revealed the participation of hydrophobic forces in the binding process. The binding of EGCG would increase the compactness of protein molecule and diminish the crevice near the heme cavity, which was responsible for the reduction of met-Hb to oxy-Hb and inhibition of hemin release from met-Hb. Moreover, EGCG efficiently suppressed Hb-caused lipid oxidation in liposomes and cod muscles, which was possibly attributed to the reduction to oxy-Hb state and declined hemin dissociation from met-Hb. Altogether, our results provide significant insights into the binding of EGCG to redox-active Hb, which represents a novel mechanism for the anti-oxidant capacity of EGCG in human health and is favorable to the applications of natural EGCG in the good quality of Hb-containing products., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate the potential therapeutic applications of (+)-catechin in the treatment of neuropathic pain. In vivo study, 32 SD rats were randomly divided into four groups: sham group, chronic constriction injury (CCI) group, CCI + ibuprofen group and CCI+ (+)-catechin group. They were subjected to behavioural tests, ELISA, immunohistochemistry and Western blotting. The mechanisms involved were investigated using specific inhibitors in cell experiments. Results of in vivo experiments showed that (+)-catechin could reduce the cold sensitivity pain in a rat model of CCI; ELISA and immunohistochemistry results showed that (+)-catechin could decrease the levels of IL-8, IL-6, TNF-α, CCL2 and CCL5 in serum and the expression levels of nNOS, COX2, IL6, TNF-α, IBA-1 and CSF1R in DRG of CCI rats. Finally, western blot confirmed that (+)-catechin could diminish the levels of IL-34/CSF1R/JAK2/STAT3 signalling pathway in DRG of CCI rats. In vitro studies showed that (+)-catechin reduced IL-34 secretion in LPS-induced RSC96 cells. Meanwhile, (+)-catechin administration in LPS-induced Schwann cell-conditioned medium (L-CM) significantly inhibited the proliferation and migration of RAW264.7 cells; in addition, L-CM+(+)-catechin reduced the activation of the CSF1R/JAK2/STAT3 signalling pathway. (+)-Catechin attenuated the Schwann cell-macrophage cascade response in the DRG by modulating the IL34/CSFIR axis and inhibiting activation of the JAK2/STAT3 pathway, thereby attenuating CCI-induced neuropathic pain in rats., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Epigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats., Methods and Materials: PE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50 mg/kg (High, H) from gestational day (GD) 6-17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured., Results: EGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG., Conclusion: EGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1., Competing Interests: Declaration of Competing Interest Authors declare that no conflict of interests are involved in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inflammatory bowel disease (IBD) is a recurrent chronic intestinal disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Its pathogenesis involves intricate interactions between pathogenic microorganisms, native intestinal microorganisms, and the intestinal immune system via the oral-gut axis. The strong correlation observed between oral diseases and IBD indicates the potential involvement of oral pathogenic microorganisms in IBD development. Consequently, therapeutic strategies targeting the proliferation, translocation, intestinal colonization and exacerbated intestinal inflammation of oral microorganisms within the oral-gut axis may partially alleviate IBD. Tea consumption has been identified as a contributing factor in reducing IBD, with epigallocatechin gallate (EGCG) being the primary bioactive compound used for IBD treatment. However, the precise mechanism by which EGCG mediates microbial crosstalk within the oral-gut axis remains unclear. In this review, we provide a comprehensive overview of the diverse oral microorganisms implicated in the pathogenesis of IBD and elucidate their colonization pathways and mechanisms. Subsequently, we investigated the antibacterial properties of EGCG and its potential to attenuate microbial translocation and colonization in the gut, emphasizing its role in attenuating exacerbations of IBD. We also elucidated the toxic and side effects of EGCG. Finally, we discuss current strategies for enhancing EGCG bioavailability and propose novel multi-targeted nano-delivery systems for the more efficacious management of IBD. This review elucidates the role and feasibility of EGCG-mediated modulation of the oral-gut axis microbiota in the management of IBD, contributing to a better understanding of the mechanism of action of EGCG in the treatment of IBD and the development of prospective treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Background: The proinflammatory response induced by macrophages plays a crucial role in the development of sepsis and the resulting multiorgan dysfunction. Identifying new regulatory targets for macrophage homeostasis and devising effective treatment strategies remains a significant challenge in contemporary research., Purpose: This study aims to identify new regulatory targets for macrophage homeostasis and develop effective strategies for treating sepsis., Study Design and Methods: Macrophage infiltration in septic patients and in lungs, kidneys, and brains of caecum ligation and puncture (CLP)-induced septic mice was observed using CIBERSORT and immunofluorescence (IF). Upon integrating the MSigDB database and GSE65682 dataset, differently expressed macrophage-associated genes (DEMAGs) were identified. Critical DEMAGs were confirmed through machine learning. The protein level of the critical DEMAG was detected in PBMCs of septic patients, RAW264.7 cells, and mice lungs, kidneys, and brains using ELISA, western blot, immunohistochemistry, and IF. siRNA was applied to investigate the effect of the critical DEMAG in RAW264.7 cells. A natural product library was screened to find a compound targeting the critical DEMAG protein. The binding of compounds and proteins was analyzed through molecular docking, molecular dynamics simulations, CETSA, and MST analysis. The therapeutic efficacy of the compounds against sepsis was then evaluated through in vitro and in vivo experiments., Results: Macrophage infiltration was inversely correlated with survival in septic patients. The critical differentially expressed molecule RasGRP1 was frequently observed in the PBMCs of septic patients, LPS-induced RAW264.7 cells, and the lungs, kidneys, and brains of septic mice. Silencing RasGRP1 alleviated proinflammatory response and oxidative stress in LPS-treated RAW264.7 cells. Catechin Hydrate (CH) was identified as an inhibitor of RasGRP1, capable of maintaining macrophage homeostasis and mitigating lung, kidney, and brain damage during sepsis., Conclusion: This study demonstrates that RasGRP1, a novel activator of macrophage proinflammatory responses, plays a crucial role in the excessive inflammation and oxidative stress associated with sepsis. CH shows potential for treating sepsis by inhibiting RasGRP1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Maintenance of NAD pools is critical for neuronal survival. The capacity to maintain NAD pools declines in neurodegenerative disease. We identify that low NMNAT2, the critical neuronal NAD producing enzyme, drives retinal susceptibility to neurodegenerative insults. As proof of concept, gene therapy over-expressing full length human NMNAT2 is neuroprotective. To pharmacologically target NMNAT2, we identify that epigallocatechin gallate (EGCG) can drive NAD production in neurons through an NMNAT2 and NMN dependent mechanism. We confirm this by pharmacological and genetic inhibition of the NAD-salvage pathway. EGCG is neuroprotective in rodent (mixed sex) and human models of retinal neurodegeneration. As EGCG has poor drug-like qualities, we use it as a tool compound to generate novel small molecules which drive neuronal NAD production and provide neuroprotection. This class of NMNAT2 targeted small molecules could have an important therapeutic impact for neurodegenerative disease following further drug development., (© 2024. The Author(s).)

Long-term exposure to hyperglycemic conditions leads to β-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of β-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus., (© 2024. The Author(s).)

Chronic obesity is an alarmingly growing global public health concern, posing substantial challenges for the prevention of chronic diseases, including hyperinsulinemia, type 2 diabetes, hyperlipidemia, hypertension, and coronary artery disease, and there is an urgent need for early mitigation strategies. We previously reported the obesity-reducing effects of green tea and β-cryptoxanthin intake. However, since tea has a complex mixture of compounds, it remained unclear which component contributed the most to this effect. Using high-performance liquid chromatography, we analyzed the components of tea in this study to determine if consumption of any combination of these compounds with β-cryptoxanthin had an obesity-reducing effect. Consuming epigallocatechin gallate (EGCG), a component of green tea, and β-cryptoxanthin for 4 weeks led to a decrease in body weight. Moreover, the weight and size of the white adipose tissues were significantly reduced, and blood biochemistry test results were comparable to normal values, with particular improvement in liver function. This indicated that intake of EGCG and β-cryptoxanthin reduces obesity in both subcutaneous and visceral fat. These findings suggest that simultaneous intake of EGCG and β-cryptoxanthin not only reduces obesity but also has a systemic beneficial effect on the body's normal physiological function.

Chemotherapy-induced oral mucositis (CIOM) is a prevalent complication of chemotherapy and significantly affects the treatment process. However, effective treatment for CIOM is lacking due to the unique environment of the oral cavity and the single effect of current drug delivery systems. In this present study, we propose an innovative approach by combining a methacrylate-modified human recombinant collagen III (rhCol3MA) hydrogel system with hyaluronic acid-epigallocatechin gallate (HA-E) and dopamine-modified methacrylate-alginate (AlgDA-MA). HA-E is used as an antioxidant and anti-inflammatory agent and synergizes with AlgDA-MA to improve the wet adhesion of hydrogel. The results of rhCol3MA/HA-E/AlgDA-MA (Col/HA-E/Alg) hydrogel demonstrate suitable physicochemical properties, excellent wet adhesive capacity, and biocompatibility. Notably, the hydrogel could promote macrophage polarization from M1 to M2 and redress human oral keratinocyte (HOK) inflammation by inhibiting NF-κB activation. Wound healing evaluations in vivo demonstrate that the Col/HA-E/Alg hydrogel exhibits a pro-repair effect by mitigating inflammatory imbalances, fostering early angiogenesis, and facilitating collagen repair. In summary, the Col/HA-E/Alg hydrogel could serve as a promising multifunctional dressing for the treatment of CIOM.

Pulmonary fibrosis is a formidable challenge in chronic and age-related lung diseases. Myofibroblasts secrete large amounts of extracellular matrix and induce pro-repair responses during normal wound healing. Successful tissue repair results in termination of myofibroblast activity via apoptosis; however, some myofibroblasts exhibit a senescent phenotype and escape apoptosis, causing over-repair that is characterized by pathological fibrotic scarring. Therefore, the removal of senescent myofibroblasts using senolytics is an important method for the treatment of pulmonary fibrosis. Procyanidin C1 (PCC1) has recently been discovered as a senolytic compound with very low toxicity and few side effects. This study aimed to determine whether PCC1 could improve lung fibrosis by promoting apoptosis in senescent myofibroblasts and to investigate the mechanisms involved. The results showed that PCC1 attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. In addition, we found that PCC1 inhibited extracellular matrix deposition and promoted the apoptosis of senescent myofibroblasts by increasing PUMA expression and activating the BAX signaling pathway. Our findings represent a new method of pulmonary fibrosis management and emphasize the potential of PCC1 as a senotherapeutic agent for the treatment of pulmonary fibrosis, providing hope for patients with pulmonary fibrosis worldwide. Our results advance our understanding of age-related diseases and highlight the importance of addressing cellular senescence in treatment., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Early studies have shown that the gut microbiota is a critical target during cadmium exposure. The prebiotic activity of epigallocatechin-3-gallate (EGCG) plays an essential role in treating intestinal inflammation and damage. However, the exact intestinal barrier protection mechanism of EGCG against cadmium exposure remains unclear. In this experiment, four-week-old mice were exposed to cadmium (5 mg kg -1 ) for four weeks. Through 16 S rDNA analysis, we found that cadmium disrupted the gut microbiota and inhibited the indole metabolism pathway of tryptophan (TRP), which serves as the principal microbial production route for endogenous ligands to activate the aryl hydrocarbon receptor (AhR). Additionally, cadmium downregulated the intestinal AhR signaling pathway and harmed the intestinal barrier function. Treatment with EGCG (20 mg kg -1 ) and the AhR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) (1 μg/d) significantly activated the AhR pathway and alleviated intestinal barrier injury. Notably, EGCG partially restored the gut microbiota and upregulated the TRP-indole metabolism pathway to increase the level of indole-related AhR agonists. Our findings demonstrate that cadmium dysregulates common gut microbiota to disrupt TRP metabolism, impairing the AhR signaling pathway and intestinal barrier. EGCG reduces cadmium-induced intestinal functional impairment by intervening in the intestinal microbiota to metabolize AhR agonists. This study offers insights into the toxic mechanisms of environmental cadmium and a potential mechanism to protect the intestinal barrier with EGCG., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dental caries is a chronic and destructive disease and matrix metalloproteinase-2 (MMP-2) plays a major role in caries. The inhibitory mechanisms of theaflavins [theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B), and theaflavin-3,3'-digallate (TF3)] on MMP-2 were investigated using techniques such as enzyme inhibition kinetics, multi-spectral methods, molecular docking, and molecular dynamics simulations. The results showed that TF1, TF2A, TF2B, and TF3 all competitively and reversibly inhibited MMP-2 activity. Fluorescence spectra and molecular docking indicated that four theaflavins spontaneously bind to MMP-2 through noncovalent interactions, driven by hydrogen bonds and hydrophobic interactions, constituting a static quenching mechanism and resulting in an altered tryptophan residue environment around MMP-2. Molecular dynamic simulations demonstrated that four theaflavins can form stable, compact complexes with MMP-2. In addition, the order of theaflavins' ability to inhibit MMP-2 was found to be TF1 > TF2B > TF2A > TF3. Interestingly, the order of binding capacity between MMP-2 and TF1, TF2A, TF2B, and TF3 was consistent with the order of inhibitory capacity, and was opposite to the order of steric hindrance of theaflavins. This may be due to the narrow space of the active pocket of MMP-2, and the smaller the steric hindrance of theaflavins, the easier it is to enter the active pocket and bind to MMP-2. This study provided novel insights into theaflavins as functional components in the exploration of natural MMP-2 inhibitors.

One of the main interests in the food industry is the preservation of food from spoilage by microorganisms or lipid oxidation. A novel alternative is the development of additives of natural origin with dual activity. In the present study, a chemically modified lysozyme (Lys) with epigallocatechin gallate (EGCG) was developed to obtain a conjugate (Lys-EGCG) with antibacterial/antioxidant activity to improve its properties and increase its application potential. The modification reaction was carried out using a free radical grafting method for the Lys modification reaction, using ascorbic acid and hydrogen peroxide as radical initiators in an aqueous medium. The synthesis of Lys-EGCG conjugate was confirmed by spectroscopic (FT-IR, 1 H-RMN, and XPS) and calorimetry differential scanning (DSC) analyses. The EGCG binding to the Lys biomolecule was quantified by the Folin-Ciocalteu method; the antibacterial activity was evaluated by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MCB) against Staphylococcus aureus and Pseudomonas fluorescens; the antioxidant activity was evaluated by ABTS, DPPH, and FRAP. The spectroscopic results showed that the Lys-EGCG conjugate was successfully obtained, and the DSC analysis revealed a 20 °C increase (P < 0.05) in the denaturation temperature of Lys due to EGCG modification. The EGCG concentration in Lys-EGCG was 97.97 ± 4.7 µmol of EGCG/g of sample. The antibacterial and antioxidant activity of the Lys-EGCG conjugate was higher (P < 0.05) than pure EGCG and Lys. The chemical modification of Lys with EGCG allows for the bioconjugate with a dual function (antibacterial/antioxidant), broadening the range of Lys and EGCG applications to different areas such as food, cosmetic, and pharmaceutical industries., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia&#95;Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium , resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.

Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of β-cyclodextrin (β-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from β-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE -/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.

Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.