Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.

The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.

Orally administrated liquid metal agents for inflammation-targeted alleviation of inflammatory bowel diseases.

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_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.

Intestinal Epithelial Co-Culture Sensitivity to Pro-Inflammatory Stimuli and Polyphenols Is Medium-Independent.

The complexification of in vitro models requires the compatibility of cells with the same medium. Since immune cells are the most sensitive to growth conditions, growing intestinal epithelial cells in their usual medium seems to be necessary. This work was aimed at comparing the sensitivity of these epithelial cells to pro-inflammatory stimuli but also to dietary polyphenols in both DMEM and RPMI-1640 media. Co-cultures of Caco-2 and HT29-MTX cells were grown for 21 days in the two media before their stimulation with a cocktail of TNF-α (20 ng/mL), IL-1ß (1 ng/mL), and IFN-γ (10 ng/mL) or with LPS (10 ng/mL) from E. coli (O111:B4). The role of catechins (15 µM), a dietary polyphenol, was evaluated after its incubation with the cells before their stimulation for 6 h. The RPMI-1640 medium did not alter the intensity of the inflammatory response observed with the cytokines. By contrast, LPS failed to stimulate the co-culture in inserts regardless of the medium used. Lastly, catechins were unable to prevent the pro-inflammatory response observed with the cytokines in the two media. The preservation of the response of this model of intestinal epithelium in RPMI-1640 medium is promising when considering its complexification to evaluate the complex cellular crosstalk leading to intestinal homeostasis.

Inhibition of Cancer Stem-like Cells by Curcumin and Other Polyphenol Derivatives in MDA-MB-231 TNBC Cells.

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is highly aggressive. Despite an initial positive response to chemotherapy, most patients experience rapid disease progression leading to relapse and metastasis. This is attributed to the presence of breast cancer stem cells (BCSCs) within the tumor, which are characterized by self-renewal, pluripotency, and resistance mechanisms. Targeting BCSCs has become critical as conventional therapies fail to eradicate them due to a lack of specific targets. Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs. The use of curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects. The aim of this study was to evaluate the cellular and molecular effects of six synthetic compounds derived from the natural polyphenol epigallocatechin gallate (EGCG) (TL1, TL2) and curcumin derivatives (TL3, TL4, TL5, and TL6) on a TNBC mesenchymal stem-like cell line. The activity of the compounds against BCSCs was also determined by a mammosphere inhibition assay and studying different BCSC markers by Western blotting. Finally, a drug combination assay was performed with the most promising compounds to evaluate their potential synergistic effects with the chemotherapeutic agents doxorubicin, cisplatin, and paclitaxel. The results showed that compounds exhibited specific cytotoxicity against the TNBC cell line and BCSCs. Interestingly, the combination of the curcumin derivative TL3 with doxorubicin and cisplatin displayed a synergistic effect in TNBC cells.

Analysis of the Antimicrobial Activity of Epigallocatechin-3-Gallate (EGCG).

We studied antimicrobial activity of epigallocatechin-3-gallate (EGCG), a green tea polyphenolic catechin, and its combined use with ceftazidime (CAZ) against bacterial strains of Klebsiella pneumoniae. EGCG exhibited no activity against strains of K. pneumoniae with a different sensitivity to CAZ. However, for a "sensitive" strain, a decrease in minimum inhibitory concentration (MIC) of CAZ (from 0.064 to 0.023 mg/liter) was revealed when CAZ was co-administered with EGCG. For a "resistant" stain, MIC of CAZ remained high, but activation of EGCG at its high concentrations was observed. Indirect evidence of antimicrobial effect of EGCG co-administered with CAZ on Klebsiella was obtained.

Procyanidin C1 inhibits bleomycin-induced pulmonary fibrosis in mice by selective clearance of senescent myofibroblasts.

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.

Epigallocatechin gallate attenuated high glucose-induced pancreatic beta cell dysfunction by modulating DRP1-mediated mitochondrial apoptosis pathways.

Long-term exposure to hyperglycemic conditions leads to ß-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of ß-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.

Gut microbiota-mediated metabolism of green tea catechins and the biological consequences: An updated review.

Multiple beneficial effects have been attributed to green tea catechins (GTCs). However, the bioavailability of GTCs is generally low, with only a small portion directly absorbed in the small intestine. The majority of ingested GTCs reaches the large intestinal lumen, and are extensively degraded via biotransformation by gut microbiota, forming many low-molecular-weight metabolites such as phenyl-γ-valerolactones, phenolic acids, butyrate, and acetate. This process not only improves the overall bioavailability of GTC-derived metabolites but also enriches the biological activities of GTCs. Therefore, the intra- and inter-individual differences in human gut microbiota as well as the resulting biological contribution of microbial metabolites are crucial for the ultimate health benefits. In this review, the microbial degradation of major GTCs was characterized and an overview of the in vitro models used for GTC metabolism was summarized. The intra- and inter-individual differences of human gut microbiota composition and the resulting divergence in the metabolic patterns of GTCs were highlighted. Moreover, the potential beneficial effects of GTCs and their gut microbial metabolites were also discussed. Overall, the microbial metabolites of GTCs with higher bioavailability and bioactive potency are key factors for the observed beneficial effects of GTCs and green tea consumption.

Advances in the Anti-Atherosclerotic Mechanisms of Epigallocatechin Gallate.

Atherosclerosis (AS) is a common clinical sickness and the major pathological basis of ischemic cardiocerebrovascular diseases (CCVDs). The pathogenesis of AS involves a variety of risk factors, and there is a lack of effective preventive and curative drugs that can completely treat AS. In recent years, with the improvement of people's living standards and changes in dietary habits, the morbidity and mortality rates of AS are on the rise, and the age of onset tends to be younger. The formation of AS is closely related to a variety of factors, and the main factors include lipid metabolism disorders, endothelial damage, inflammation, unstable plaques, etc. Epigallocatechin gallate (EGCG), as one of the main components of catechins, has a variety of pharmacological effects, and its role in the prevention of AS and the protection of cardiovascular and cerebral blood vessels has been highly valued. Recent epidemiological investigations and various in vivo and ex vivo experiments have shown that EGCG is capable of resisting atherosclerosis and reducing the morbidity and mortality of AS. In this paper, we reviewed the anti-AS effects of EGCG and its mechanisms in recent years, including the regulation of lipid metabolism, regulation of intestinal flora disorders, improvement of vascular endothelial cell functions, inhibition of inflammatory factors expression, regulation of inflammatory signaling pathways, inhibition of matrix metalloproteinase (MMP) expression, and inhibition of platelet aggregation, which are helpful for the prevention of cardiocerebrovascular diseases.

Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer.

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.

Application of In Situ Mucoadhesive Hydrogel with Anti-Inflammatory and Pro-Repairing Dual Properties for the Treatment of Chemotherapy-Induced Oral Mucositis.

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.

Conjugation of Lysozyme and Epigallocatechin Gallate for Improving Antibacterial and Antioxidant Properties.

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, 1H-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.

Pruned tea biomass plays a significant role in functional food production: A review on characterization and comprehensive utilization of abandon-plucked fresh tea leaves.

Tea is the second largest nonalcoholic beverage in the world due to its characteristic flavor and well-known functional properties in vitro and in vivo. Global tea production reaches 6.397 million tons in 2022 and continues to rise. Fresh tea leaves are mainly harvested in spring, whereas thousands of tons are discarded in summer and autumn. Herein, pruned tea biomass refers to abandon-plucked leaves being pruned in the non-plucking period, especially in summer and autumn. At present, no relevant concluding remarks have been made on this undervalued biomass. This review summarizes the seasonal differences of intrinsic metabolites and pays special attention to the most critical bioactive and flavor compounds, including polyphenols, theanine, and caffeine. Additionally, meaningful and profound methods to transform abandon-plucked fresh tea leaves into high-value products are reviewed. In summer and autumn, tea plants accumulate much more phenols than in spring, especially epigallocatechin gallate (galloyl catechin), anthocyanins (catechin derivatives), and proanthocyanidins (polymerized catechins). Vigorous carbon metabolism induced by high light intensity and temperature in summer and autumn also accumulates carbohydrates, such as soluble sugars and cellulose. The characteristics of abandon-plucked tea leaves make them not ideal raw materials for tea, but suitable for novel tea products like beverages and food ingredients using traditional or hybrid technologies such as enzymatic transformation, microbial fermentation, formula screening, and extraction, with the abundant polyphenols in summer and autumn tea serving as prominent flavor and bioactive contributors.

Walnut protein isolate-epigallocatechin gallate nanoparticles: A functional carrier enhanced stability and antioxidant activity of lycopene.

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 EC50 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.

Assessment of the Diuretic Properties of Rice Bean Accessions Using a Mouse Model and Identification of Active Polyphenolic Compounds.

Rice bean [Vigna umbellata (Thunb.) Ohwi and Ohashi], an annual legume in the genus Vigna, is a promising crop suitable for cultivation in a changing climate to ensure food security. It is also a medicinal plant widely used in traditional Chinese medicine; however, little is known about the medicinal compounds in rice bean. In this study, we assessed the diuretic effect of rice bean extracts on mice as well as its relationship with the contents of eight secondary metabolites in seeds. Mice gavaged with rice bean extracts from yellow and black seeds had higher urinary output (5.44-5.47 g) and water intake (5.8-6.3 g) values than mice gavaged with rice bean extracts from red seeds. Correlation analyses revealed significant negative correlations between urine output and gallic acid (R = -0.70) and genistein (R = -0.75) concentrations, suggesting that these two polyphenols negatively regulate diuresis. There were no obvious relationships between mice diuresis-related indices (urine output, water intake, and weight loss) and rutin or catechin contents, although the concentrations of both of these polyphenols in rice bean seeds were higher than the concentrations of the other six secondary metabolites. Our study findings may be useful for future research on the diuretic effects of rice bean, but they should be confirmed on the basis of systematic medical trials.

Whey Protein Sodium-Caseinate as a Deliverable Vector for EGCG: In Vitro Optimization of Its Bioaccessibility, Bioavailability, and Bioactivity Mode of Actions.

Epigallocatechin gallate (EGCG), the principal catechin in green tea, exhibits diverse therapeutic properties. However, its clinical efficacy is hindered by poor stability and low bioavailability. This study investigated solid particle-in-oil-in-water (S/O/W) emulsions stabilized by whey protein isolate (WPI) and sodium caseinate (NaCas) as carriers to enhance the bioavailability and intestinal absorption of EGCG. Molecular docking revealed binding interactions between EGCG and these macromolecules. The WPI- and NaCas-stabilized emulsions exhibited high encapsulation efficiencies (>80%) and significantly enhanced the bioaccessibility of EGCG by 64% compared to free EGCG after simulated gastrointestinal digestion. Notably, the NaCas emulsion facilitated higher intestinal permeability of EGCG across Caco-2 monolayers, attributed to the strong intermolecular interactions between caseins and EGCG. Furthermore, the emulsions protected Caco-2 cells against oxidative stress by suppressing intracellular reactive oxygen species generation. These findings demonstrate the potential of WPI- and NaCas-stabilized emulsions as effective delivery systems to improve the bioavailability, stability, and bioactivity of polyphenols like EGCG, enabling their applications in functional foods and nutraceuticals.

Simultaneous Determination of Four Catechins in Black Tea via NIR Spectroscopy and Feature Wavelength Selection: A Novel Approach.

As a non-destructive, fast, and cost-effective technique, near-infrared (NIR) spectroscopy has been widely used to determine the content of bioactive components in tea. However, due to the similar chemical structures of various catechins in black tea, the NIR spectra of black tea severely overlap in certain bands, causing nonlinear relationships and reducing analytical accuracy. In addition, the number of NIR spectral wavelengths is much larger than that of the modeled samples, and the small-sample learning problem is rather typical. These issues make the use of NIRS to simultaneously determine black tea catechins challenging. To address the above problems, this study innovatively proposed a wavelength selection algorithm based on feature interval combination sensitivity segmentation (FIC-SS). This algorithm extracts wavelengths at both coarse-grained and fine-grained levels, achieving higher accuracy and stability in feature wavelength extraction. On this basis, the study built four simultaneous prediction models for catechins based on extreme learning machines (ELMs), utilizing their powerful nonlinear learning ability and simple model structure to achieve simultaneous and accurate prediction of catechins. The experimental results showed that for the full spectrum, the ELM model has better prediction performance than the partial least squares model for epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). For the feature wavelengths, our proposed FIC-SS-ELM model enjoys higher prediction performance than ELM models based on other wavelength selection algorithms; it can simultaneously and accurately predict the content of EC (Rp2 = 0.91, RMSEP = 0.019), ECG (Rp2 = 0.96, RMSEP = 0.11), EGC (Rp2 = 0.97, RMSEP = 0.15), and EGCG (Rp2 = 0.97, RMSEP = 0.35) in black tea. The results of this study provide a new method for the quantitative determination of the bioactive components of black tea.

Zinc Treatment of Tea Plants Improves the Synthesis of Trihydroxylated Catechins via Regulation of the Zinc-Sensitive Protein CsHIPP3.

The tea plant (Camellia sinensis [L.] O. Kussntze) is a global economic crop. Zinc treatment of tea plants can enhance catechin biosynthesis. However, the underlying molecular mechanism behind catechin formation through zinc regulation remains unclear. This study identified a zinc-responsive protein, C. sinensis heavy metal-associated isoprenylated plant protein 3 (CsHIPP3), from zinc-treated tea seedlings. CsHIPP3 expression was positively correlated with trihydroxylated catechin (TRIC) content. CsF3'5'H1 is a crucial regulator of the TRIC synthesis pathway. The interaction between CsHIPP3 and CsF3'5'H1 was assessed using bimolecular fluorescence complementation, firefly luciferase complementation imaging, and pulldown experiments. CsHIPP3 knockdown using virus-induced gene silencing technology decreased the content of each component of TRICs. Compared with the control, the relative catechin content was reduced by 40.12-55.39%. Co-overexpression of CsHIPP3 and CsF3'5'H1 significantly elevated the TRIC content in tea leaves and calli. Moreover, the TRIC content in transient co-overexpression leaves was 1.44-fold higher than that of the control group, and tea callus was 50.83% higher in transient co-overexpression than in the wild type. Thus, zinc-regulated TRIC synthesis in a zinc-rich environment was mediated by binding CsHIPP3 with CsF3'5'H1 to promote TRIC synthesis and accumulation.

Epigallocatechin-3-gallate Inhibits LPS/AßO-induced Neuroinflammation in BV2 Cells through Regulating the ROS/TXNIP/NLRP3 Pathway.

Neuroinflammation is a key factor in cognitive dysfunction and neurodegenerative diseases such as Alzheimer's disease (AD), so inhibiting neuroinflammation is considered as a potential treatment for AD. Epigallocatechin-3-gallate (EGCG), a polyhydroxyphenol of green tea, has been found to exhibit anti-oxidative, anti-inflammatory and neuroprotective effects. The aim of this study was to investigate the inhibitory effect of EGCG on inflammation and its mechanism. In this study, BV2 cells were simultaneously exposed to lipopolysaccharides (LPS) and the amyloid-ß oligomer (AßO) to induce inflammatory microenvironments. Inflammatory cytokines and NLRP3 inflammasome-related molecules were detected by RT-PCR and Western Blot. The results show that EGCG inhibits LPS/AßO-induced inflammation in BV2 cells through regulating IL-1ß, IL-6, and TNF-α. Meanwhile, EGCG reduces the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and levels of intracellular ROS in BV2 cells treated with LPS/AßO by affecting the mitochondrial membrane potential (MMP). Further research found that EGCG inhibited MMP through regulating thioredoxin-interacting protein (TXNIP) in LPS/AßO-induced neuroinflammation. In conclusion, EGCG may alleviate LPS/AßO-induced microglial neuroinflammation by suppressing the ROS/ TXNIP/ NLRP3 pathway. It may provide a potential mechanism underlying the anti-inflammatory properties of EGCG for alleviating AD.

Catechins and caffeine absorption, and antioxidant activity of tea-macerated wine in a Caco-2 intestinal cell culture model.

A novel style of flavored wine was developed via infusion of either black tea or green tea into Chardonnay wine. The bioaccessibility and bioavailability of phenolic substances in green/black tea-infused Chardonnay wine were investigated. Catechin, caffeine, and epicatechin gallate, originating from the tea, displayed high absorption rates with apparent permeability coefficient values above 10 × 10-6 cm/s in a human Caco-2 intestinal cell model. A paracellular pathway was proposed to drive the transport of catechin and epicatechin gallate, while the possible transport pathway of caffeine is passive transcellular diffusion route. Co-supplementation of flavonoids of quercetin or naringenin (20 µM) could further enhance the uptake of catechin and epicatechin gallate, but reduce the absorption of caffeine. Great in vitro and cellular antioxidant capacities were witnessed in the tea-macerated wine samples. The wine samples also neutralized the negative impact of tert-butyl hydroperoxide (25 µM) on glutathione S-transferase and glutathione levels, apoptosis induction, and intracellular malondialdehyde levels. RNA sequencing with limma method revealed a total of 1473 and 406 differentially expressed genes in the 21-day-old Caco-2 intestinal cells treated with the green and black tea-macerated wines for 5 h respectively, indicating metabolic changes in the cells from the different wines.