Search Results (892)

Background: Squamous cell carcinoma of head and neck (SCCHN) is a devastating disease with high morbidity and mortality and the 6th most common cancer worldwide. The 5-year relative survival for advanced-stage disease is below 50%, stressing the need for chemoprevention. In the current study, we investigated the chemopreventive efficacy of the combination of resveratrol and epigallocatechin gallate (EGCG). Methods: We used the 4-Nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis model. C57BL/6 mice were exposed to drinking water containing 4-NQO for 10 weeks. From week 11, mice were treated with vehicle, resveratrol, EGCG and their combination until week 22. RNASeq, qPCR and in silico analysis were performed identifying differentially expressed genes and enriched pathways. Results: Resveratrol alone and in combination with EGCG significantly inhibited the number of visible lesions, whereas the number of microscopic lesions and lesion areas were significantly inhibited only by the combination. The expression of Ki-67 was also significantly inhibited in resveratrol and combination groups. Growth differentiation factor 15 (GDF15), Activation transcription factor 3 (ATF3) and several other genes associated with xenobiotic metabolism as significantly upregulated genes, with GDF15 being the most upregulated one. Furthermore, hallmarks of xenobiotic metabolism and several other anticancer pathways were enriched after treatment with resveratrol and the combination. Conclusions: Our data strongly demonstrate the chemopreventive potential of the combination of resveratrol and EGCG and pave the way for further clinical developments. Full article

The cytotoxic effect of islet amyloid polypeptide (IAPP) misfolding and aggregation has a well-recognized role in the pathogenesis of type 2 diabetes mellitus, mediated by failure of the beta cell’s protein quality control system to rescue the cell from overwhelming proteotoxic stress induced by IAPP aggregates, ultimately leading to apoptosis. A small but growing body of research also links IAPP-mediated proteotoxic stress to the pathogenesis of type 1 diabetes and to the functional decline of transplanted islets. Among the most promising therapeutic approaches under investigation are small organic molecules that may act as direct chemical chaperones to prevent IAPP aggregation, promote the activity of endogenous chaperones, or alter gene networks of the unfolded protein response (UPR) to promote pro-survival rather than pro-apoptotic pathways in response to IAPP-mediated proteotoxic stress. Compounds warranting special attention include 4-phenylbutyrate (PBA), tauroursodeoxycholic acid (TUDCA), and epigallocatechin gallate (EGCG), as each has a growing body of evidence supporting their ability to ameliorate this process, and given that each of these are already known to have good safety profiles in humans, potentially accelerating the timeline to interventional studies. This review explores the evidence for IAPP-mediated proteotoxicity in multiple forms of diabetes, the mechanisms of cytotoxicity at different levels of the cell’s protein quality control systems, how these small organic compounds may act on these processes including new insights on the role of thioredoxin-interacting protein (TXNIP), and the current evidence supporting each of these compounds in mitigating diabetogenesis. Full article

Aquaporins (AQPs) are increasingly recognized as key regulators of tumor progression, influencing key hallmarks of cancer progression and cellular homeostasis. Their frequent overexpression in malignancies highlights their potential as therapeutic targets, yet the development of selective synthetic inhibitors remains challenging due to structural conservation and off-target toxicity. Natural compounds have recently emerged as promising modulators of AQP expression and function, offering greater molecular diversity and generally favorable safety profiles. This review synthesizes current evidence on phytochemicals, including bacopaside II, curcumin, resveratrol, quercetin, EGCG, all-trans retinoic acid, chrysin, and rottlerin, that interact with AQP isoforms relevant to cancer biology. These agents regulate AQPs through transcriptional control, redox modulation, signaling-pathway interference, or direct pore blockade, thereby attenuating oncogenic processes such as migration, angiogenesis, inflammation, and metabolic adaptation. Several compounds, notably bacopaside II and rottlerin, display isoform-selective inhibitory properties that directly impair AQP1- and AQP3-mediated permeability. Collectively, available evidence positions natural AQP modulators as promising lead compounds providing scaffolds for further drug development in oncology. Continued structural, mechanistic, and preclinical research is required to optimize isoform specificity and therapeutic efficacy, paving the way for their integration into future anticancer strategies. Full article

Background: Despite significant improvements in blood safety, the risk of transfusion-transmitted infections persists, particularly from emerging and re-emerging viruses. For red blood cell (RBC) products, this risk is exacerbated by the fact that there is no routine testing for many of these pathogens, and effective, commercially available pathogen inactivation technologies specifically for RBCs are still lacking. This gap in the safety framework means that viruses capable of establishing an asymptomatic viremia—a characteristic of many arboviruses like Zika, dengue, and West Nile virus—present a tangible threat to the blood supply, highlighting the need for broad-spectrum countermeasures. Study Design and Methods: This study aims to investigate the antiviral activity of green tea extract (GTE) and its key catechins, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), against ZIKV in both cellular models and red blood cell (RBC) products. In vitro antiviral activity was assessed using A549 cells treated with GTE (150 μg/mL) or purified EGCG/ECG (20 μM). Mechanistic studies focused on viral attachment inhibition. Additionally, ZIKV-spiked RBC products were co-incubated with GTE (300 μg/mL) for 1 h to evaluate virucidal effects. Erythrocyte integrity was confirmed via hemolysis assays. Results: Co-treatment with GTE or catechins suppressed ZIKV replication by ≥3.64 logs (p < 0.001) in A549 cells. GTE and catechins primarily inhibited viral attachment. In RBCs, GTE reduced viral infectivity by 99.99% (4-log reduction) without compromising erythrocyte membrane integrity or cellular viability. Furthermore, RBCs with added GTE demonstrated a lower hemolysis rate during storage for up to 60 days. Conclusions: GTE exhibits potent virucidal activity against ZIKV in blood matrices, highlighting its potential as a pathogen reduction agent to enhance transfusion safety. Further development of GTE-based additive solutions or technologies is warranted. Full article

(−)-Epigallocatechin 3-gallate (EGCG) is a potent natural antioxidant, but its strong bitterness and poor palatability limit its application in animal production. This study aimed to evaluate the protective effects and underlying mechanisms of chemically synthesized EGCG derivatives against oxidative stress using a diquat-induced mouse model. A total of 36 male ICR mice were randomly assigned into six groups (n = 6): Control (T0), Diquat (T1), EGCG + Diquat (T2), Epigallocatechin octanoate (EGCO) + Diquat (T3), Epigallocatechin p-chloromethylbenzoate (EGCP) + Diquat (T4), and Epigallocatechin ibuprofen ester (EGCI) + Diquat (T5). Oxidative stress was induced by intraperitoneal injection of diquat at day 27 of the experiment, while EGCG or its derivatives were administered via dietary supplementation. At day 28, the mice were weighed, killed, and the tissues were sampled. Diquat challenge significantly impaired growth, increased serum injury markers (ALT, AST, DAO, and D-LA) (p < 0.05), suppressed hepatic and jejunal antioxidant enzymes (GPx, SOD, and TAOC) while elevating MDA (p < 0.05), damaged jejunal morphology (villus atrophy) (p < 0.05), and downregulated tight junction proteins (ZO-1 and Occludin) (p < 0.05). Chemically synthesized EGCG derivatives, especially EGCI, effectively alleviated diquat-induced growth impairment and hepatic and intestinal oxidative damage by improving intestinal barrier function and enhancing systemic antioxidant capacity, possibly in part through activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Compared with EGCG, EGCI exhibited reduced bitterness and improved palatability, which favored normal feed intake. These findings provide strong theoretical support for the future application of EGCG derivatives, especially EGCI, as functional antioxidant additives in broiler production. Full article

The α-glucosidase inhibitory activity of Keemun black tea arises from complex interactions among its major polyphenols, which cannot be reliably predicted from the activities of isolated compounds. In this study, eight dominant polyphenols were investigated using a quantitative reconstruction–omission framework designed to reflect typical household tea brewing. The fully reconstructed system recovered approximately 72% of the inhibitory activity of the diluted native infusion, supporting the functional representativeness of the selected compounds. Systematic omission experiments revealed that antagonistic interactions, particularly among theaflavins, dominated the net inhibitory outcome, with removal of the most potent inhibitor, theaflavin-3,3′-digallate (TFDG), paradoxically increasing overall activity. Pairwise Combination Index analysis further demonstrated concentration-dependent biphasic interactions, exemplified by the epigallocatechin-3-gallate (EGCG)–TFDG pair, while molecular docking suggested overlapping binding sites as a potential structural basis for competitive inhibition. Collectively, this work provides a system-level dissection of α-glucosidase inhibition in black tea. Although the reconstructed system does not fully capture all contributions, the proposed framework offers a generalizable strategy for investigating interaction-driven bioactivity in complex dietary matrices and for further mechanistic studies. Full article

The influence of different gas compositions in modified atmospheric packaging (MAP) without and with chitooligosaccharide-EGCG (CE) conjugate on storage stability of Asian hard clam (HC) meat during storage at 4 °C was studied. Microbial load of HC meat was <5 log CFU/g when packaged under MAP, regardless of treatment, up to 18 days of storage, whereas control exceeded viable bacterial count (6 log CFU/g) on day 9. The lowest microbial load, volatile bases, and lipid oxidation were obtained in HC meat pretreated with 600 ppm of CE conjugate and MAP (80% CO₂/20% O₂) (MAP4-CE) (p < 0.05). Correlation heatmap analysis showed that a high-CO₂/low-O₂ atmosphere was the primary determinant of reduced Pseudomonas growth and lipid oxidation in HC meat, whereas the CE conjugate conferred only minor oxidation and nitrogenous spoilage indices. HC packed under MAP exhibited higher cooking and drip loss, along with increased toughness and firmness, irrespective of treatment. PUFA of MAP4-CE was retained during 18 days of storage. High-CO₂, with or without CE, redirected the microbial diversity toward CO₂-tolerant taxa. Overall, MAP4-CE had an extended shelf-life of at least 18 days while better preserving lipid quality and delayed growth of spoilage bacteria. Full article

Background: Alzheimer’s disease (AD) remains a major public health challenge. Observational associations between dietary patterns and reduced dementia risk have prompted investigations of dietary bioactives (DBs) as cognitive nutraceuticals. Methods: This critical narrative review examines interventional trials for nine prominent DBs relevant to AD: docosahexaenoic acid (DHA), curcumin, resveratrol, epigallocatechin gallate (EGCG), nicotinamide riboside (NR), tricaprilin, vitamin E (α-tocopherol), cannabinoids, and NIC5-15 (D-pinitol). Trials were identified through ClinicalTrials.gov (search date: December 2024) and supplemented by PubMed searches for published results. Data were extracted on trial phase, design, cognitive/functional endpoints, biomarker outcomes, and development status. Findings are synthesized qualitatively; no formal meta-analysis or risk of bias assessment was conducted. Results: None of the nine bioactives demonstrated consistent cognitive efficacy in AD. Phase III trials of DHA, curcumin, and tricaprilin did not meet primary cognitive endpoints. Resveratrol reduced CSF Aβ40 without cognitive benefit. Cannabinoids improved behavioral symptoms but showed no measurable cognitive effects. High-dose vitamin E slowed functional decline, while cognition remained unchanged. In contrast, trials in preclinical or at-risk populations reported preliminary cognitive signals for EGCG and biomarker engagement for NR, suggesting potential for early intervention. Conclusions: Current clinical evidence does not support high-dose DBs supplementation as an effective treatment for AD. Predominantly negative late-phase findings highlight limitations, with potential contributors including limited bioavailability, late intervention, insufficient target engagement, and biological heterogeneity. Future research may benefit from early biomarker-defined populations, optimized formulations, multi-nutrient or dietary approaches, and precision nutrition strategies considering genetic risk and baseline nutrient status. DBs may be better positioned for prevention or early-stage intervention rather than late-stage therapy. Full article

Salivary aldehyde dehydrogenases (ALDHs), particularly ALDH3A1 and ALDH1A1, serve as frontline enzymatic defenses in the oral cavity, detoxifying reactive aldehydes generated through metabolic activity, microbial fermentation, and environmental exposures. These enzymes are essential for maintaining redox homeostasis, mucosal integrity, and immune modulation. However, under chronic metabolic stress, such as in diabetes, oral inflammation, and cancer, salivary ALDHs become vulnerable to non-enzymatic glycation by reactive carbonyl species like methylglyoxal. This modification impairs cofactor binding, catalytic activity, and structural stability, thereby compromising detoxification capacity at a time of heightened aldehyde burden. This review provides the first insights into ALDH glycation and particularly that of salivary ALDH, examining its structural mechanisms, disease-specific consequences, and emerging protective strategies. Special focus is given to natural compounds, including curcumin, thymoquinone, resveratrol, carnosine, and EGCG, that prevent glycation or restore ALDH function via carbonyl scavenging, antioxidant activation, and NAD⁺/SIRT1 pathway modulation. We also highlight critical research gaps, such as the absence of site-specific glycation maps, lack of salivary gland-based models, and limited availability of ALDH3A1-specific activators. Importantly, we propose that the glycation status of salivary ALDHs may serve as a non-invasive biomarker of oxidative stress and therapeutic response in metabolic and inflammatory disorders. By bridging biochemical insights with translational potential, this review establishes ALDH glycation as a mechanistic and clinically actionable axis in oral and systemic health. Full article

Tea offers health benefits, but some teas accumulate high fluoride (F), posing fluorosis risks. However, the roles of individual tea components in regulating F bioavailability remain unclear. This study investigated the effects of major tea constituents on F metabolism in male rats (n = 5/group) administered F (40 mg/L) alone or with graded doses of epigallocatechin gallate (EGCG, 150–450 mg/kg); theaflavins, thearubigins, and theabrownin (TFs, TRs, TB, 200–800 mg/kg each); tea polysaccharides (TPSs, 25–250 mg/kg); and calcium and aluminum (Ca, Al, 800–3200 µg/kg each) via gavage. Pharmacokinetic analysis of plasma F (0–480 min) and fecal F excretion were assessed. The result showed that high-dose EGCG (450 mg/kg) reduced C_max by 61.76% and total exposure (AUC_0–t) by 37.48% compared to the control, while significantly increasing fecal F by 26.79% (p < 0.05). TB (800 mg/kg) delayed F absorption by prolonging T_max from 18 to 30 min and reduced C_max by 35.38% (p < 0.05). TPS (250 mg/kg) decreased C_max by 51.72% and AUC_0–t by 24.38% (p < 0.05). Ca and Al (800–3200 µg/kg) reduced C_max by 39.19–69.62%, and low-dose aluminum (800 µg/kg) increased fecal F by 35.58% (p < 0.05). These findings elucidate distinct roles of tea constituents in mitigating F bioavailability, providing a scientific basis for tea safety assessment and dietary interventions against F overexposure. Full article

To investigate the effect of phenolic hydroxyl group number on the interaction between catechins and a plant-derived protein carrier, four catechins with varying hydroxyl numbers—epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG)—were investigated. The new plant-derived edible dock protein (EDP) was selected as a carrier matrix. EDP, when employed as a protein delivery carrier, possessed a hydrophobic amino acid content of 45%. This structural feature enabled it to provide more hydrophobic cavities for small molecule compounds, thereby facilitating better binding with them. The results indicated that the order of loading capacity of catechins within EDP was EGCG (9.7%) > ECG (9.1%) > EGC (8.8%) > EC (7.1%). This sequence was consistent with the number of hydroxyl groups in catechin: EGCG (8) > ECG (7) > EGC (6) > EC (5). Among the four catechins, EGCG had the highest binding constant (Ka = 2.6 × 10³ L/mol), leading to the largest quenching of EDP. During self-assembly, hydrogen bonding, hydrophobic and electrostatic interactions were the main driving forces, and the interaction between EGCG and EDP was the strongest. This study indicated that the hydroxyl group number of polyphenolic compounds can determine its binding affinity with proteins. Full article

Background/Objectives: Mood disorders like depression, anxiety, and stress have increased steadily among adults, with growing interest in non-pharmaceutical treatments to improve symptomology. Epigallocatechin-3-gallate (EGCG) and curcumin are polyphenols with evidence to support their positive impacts on mood disorder symptomology and potential mood-associated biomarkers like brain-derived neurotrophic factor (BDNF). This study examined the effects of combined EGCG and curcumin supplementation on mood disturbance symptomology and serum brain-derived neurotrophic factor in adults. Methods: An 8-week randomized double-blinded placebo-controlled trial was conducted in adults (n = 64, 18–50 years old). Participants were randomized to a supplement group (n = 32; 350 mg EGCG and 1330 mg curcumin daily) or a matched placebo group (n = 32). Mood disturbance (DASS-21, GAD-7), sleep disturbance (GSAQ), and physical activity (IPAQ) were assessed at baseline, Week 4, and Week 8. Anthropometric measures, 24 h diet recalls, and fasted blood samples for serum BDNF were collected at baseline and Week 8. A multivariate ANOVA evaluated primary outcomes (DASS-21 composite score and BDNF), followed by repeated measures ANOVA for secondary outcomes (p < 0.05). Results: Significant improvements were observed across all participants for mood (DASS-21 composite and subscales, GAD-7, p < 0.001 for all), sleep (p < 0.001), and physical activity (p < 0.01), with no significant difference between supplement and placebo groups. Mean serum BDNF increased in both groups, but neither were statistically significant with no group-by-time interactions. Sugar intake (g/kg body weight) was positively correlated with mood symptoms at Week 8 in the supplement group. Baseline fruit and vegetable intake was associated with mood symptom severity at select time points; however, dietary changes during the intervention were not significantly related to changes in mood outcomes. Conclusions: Combined EGCG and curcumin supplementation did not show additional benefits beyond placebo for mood disturbance or serum BDNF over eight weeks. Observed improvements across both groups suggest that behavioral or lifestyle factors may play a larger role in short-term mood improvements than supplementation alone. Full article

The human metapneumovirus (HMPV) Fusion (F) glycoprotein is a high-priority target for “fusion-locking” agents that stabilize its metastable prefusion state. While monomeric catechins like EGCG are known antivirals, the molecular basis for the superior activity of structurally complex dimeric catechins remains poorly understood. We employed an advanced biophysical workflow, integrating 100 ns all-atom molecular dynamics (MD), free energy landscape (FEL) analysis, and MM/GBSA thermodynamic integration to decode the Structure–Dynamics Relationship (SDR) of 210 Camellia sinensis (Green tea) phytochemicals. The results reveal a “Galloylation-Driven Anchoring” mechanism: the galloyl moiety of prodelphinidin A2 3′-gallate provides critical electrostatic complementarity to the Asp325-Asp336 acidic ridge. FEL analysis quantitatively demonstrates that this anchoring leads to pronounced stabilization of the F protein in a deep, kinetically favored global minimum (ΔG = 9.357 kJ/mol), effectively raising the energy barrier for the fusogenic conformational shift. This study provides a comparative and mechanistically informed computational proof-of-concept for the use of dimeric natural scaffolds as precision fusion-locking agents, offering a roadmap for experimental biophysical validation. In this workflow, molecular docking was employed exclusively as a qualitative structure-based filtering step, while all quantitative conclusions regarding stabilization and binding energetics were derived from post-docking MD, FEL, and MM/GBSA analyses. Full article

Epigallocatechin gallate (EGCG) represents the key phenolic compound in green tea, which has been verified to possess various biological effects but suffers from low stability and poor bioavailability. To address these issues, EGCG-loaded nanoliposomes (ELs) were screened and prepared using an ethanol injection–calcium acetate gradient (EtOH-CAG) method. An encapsulation efficiency of 94.61% was achieved, involving a particle size of 118.6 nm and a polydispersity index (PDI) of 0.23. Via layer-by-layer assembly, nanoliposomes modified with either ε-polylysine (ε-PL) monolayer (ELP) or ε-polylysine/sodium alginate (SA) bilayer (ELPA) exhibited substantially improved stability. Moreover, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermal analysis confirmed the effective loading of EGCG and the successful decoration of ε-PL and SA. Molecular docking analyses of dual ligands further characterized the surface modification mechanism, which was primarily mediated by hydrogen bonding and electrostatic interactions. ELPA maintained robust stability under conditions including 200 mM salt concentration, a pH range of 4–10, temperatures up to 55 °C, and a 25-day storage duration. The modified systems showed considerably enhanced cellular uptake without causing cytotoxicity. Collectively, the developed ε-PL/SA bilayer nanoliposomes offer an eco-friendly, efficient strategy to enhance EGCG stability and in vitro bioavailability in functional food applications. Full article

Multiple sclerosis (MS) is characterized by progressive mitochondrial dysfunction affecting complexes I, III, and IV of the electron transport chain, contributing to axonal energy failure and neurodegeneration. This review examines the potential of combining β-hydroxybutyrate (βHB), epigallocatechin-3-gallate (EGCG), and ellagic acid (EA) as a multi-target therapeutic strategy to restore mitochondrial function in patients with MS. Experimental and clinical studies demonstrate that each compound exerts complementary mechanisms. Ketone bodies provide an alternative energy substrate and restore complex I activity via sirtuin-dependent pathways. EGCG acts predominantly at the peripheral level by reducing systemic inflammation and oxidative stress. EA-derived urolithins effectively cross the blood–brain barrier to directly enhance mitochondrial biogenesis and respiratory chain function in the central nervous system. Clinical trials have reported improvements in fatigue, cognition, mood, and muscle function following supplementation with these compounds. The convergence of their actions on energy restoration, reactive oxygen species reduction, and epigenetic modulation of protective pathways suggests their synergistic potential. Optimized delivery strategies, including exogenous ketone salts, liposomal EGCG, and microencapsulated EA, may overcome bioavailability limitations and interindividual variability in the gut microbiota metabolism. Full article