Search Results (98)

Objectives: To estimate the added value of dostarlimab compared to durvalumab and pembrolizumab as first-line treatment for adult patients with primary advanced or recurrent endometrial cancer (EC) in Spain using a Multi-Criteria Decision Analysis (MCDA) framework. Methods: Following the Evidence and Value: Impact on Decision Making (EVIDEM) framework and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations, 25 Spanish experts (12 medical oncologists and 13 hospital pharmacists) weighted and scored 11 quantitative and 5 qualitative criteria based on an evidence matrix from a literature review. Results: Efficacy and safety were weighted as the most important criteria. Dostarlimab showed positive added value in both comparisons with scores of 0.58 versus durvalumab/durvalumab + olaparib and 0.50 versus pembrolizumab. Dostarlimab and pembrolizumab are the only therapies reimbursed in the Spanish public health system; therefore, their comparative assessment is of clinical and strategic relevance. While pembrolizumab may show longer progression-free survival (PFS) and response duration in specific subgroups, the evidence for dostarlimab—including a statistically significant improvement in overall survival (OS) in the overall population as a primary endpoint, more robust data, and favorable long-term quality-of-life outcomes—was considered by the expert panel to support a more favorable assessment. Conclusions: Within the MCDA framework, experts consider dostarlimab an option with a higher value contribution for adult patients with primary advanced or recurrent EC. Its clinical benefits, improved quality-of-life outcomes, and alignment with healthcare priorities promote treatment continuity and adherence in clinical practice. MCDA provided a transparent approach for multidimensional evaluation of these therapies. Full article

Oxidative stress and inflammation are central environmental contributors to skin aging, accelerating extracellular matrix (ECM) breakdown and loss of dermal structure. Although Nypa fruticans is recognized for its antioxidant properties, the constituents responsible for these effects remain undefined. To address this, we screened five major polyphenols—protocatechuic acid (PA), hydroxybenzoic acid (HA), procyanidin B1 (PB), catechin (CA), and epicatechin (EC)—for protective activity in two inflammatory skin cell models: human dermal fibroblasts (HDFs) stimulated with tumor necrosis factor-α (TNF-α), and human epidermal keratinocytes (HEKs) co-stimulated with TNF-α and interferon-γ (IFN-γ). PB emerged as the most consistently active compound. In fibroblasts, it suppressed intracellular reactive oxygen species, limited matrix metalloproteinase-1 (MMP-1) release, and restored pro-collagen I α1 output. In keratinocytes, it reduced both pro-inflammatory cytokines—interleukin (IL)-6, IL-8, and IL-1β and inflammatory mediators, including prostaglandin E₂ (PGE₂), cyclooxygenase-2 (COX-2), and nitric oxide (NO). At the transcriptional level, PB shifted the ECM balance by lowering MMP expression while elevating collagen- and hyaluronan-associated genes. Collectively, these results position PB as a principal driver of the protective activity of Nypa fruticans (N. fruticans) leaves under inflammatory conditions. Mechanistically, PB suppressed nuclear factor kappa B (NF-κB) activation and promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation in keratinocytes, supporting its dual anti-inflammatory and antioxidant activities. Full article

This study presents an integrated evaluation of the organ-specific phenolic composition and antioxidant activity of Cicer isauricum. Extracts obtained from leaves, stems, and roots were analyzed using liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) and multiple in vitro antioxidant assays. LC–MS/MS analysis revealed a distinct organ-dependent distribution of phenolic compounds. Stem extracts were characterized by high levels of hyperoside (2227.97 µg/g extract), luteolin (298.22 µg/g), and eriodictyol (434.03 µg/g), while leaves were rich in hyperoside (1162.42 µg/g), hesperidin (459.40 µg/g) and kaempferol (182.88 µg/g). Root extracts were dominated by flavan-3-ols, particularly (+)-catechin (355.93 µg/g) and (–)-epicatechin (59.58 µg/g), indicating a differentiated metabolic profile. Antioxidant assays, including cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, demonstrated that root extracts exhibited the strongest activity, with the lowest IC₅₀ values (DPPH: 4.15 mg/mL; ABTS: 1.41 mg/mL) and highest reducing power (FRAP EC₅₀: 0.41 mg/mL; CUPRAC EC₅₀: 1.78 mg/mL). Correlation analysis confirmed strong associations between total phenolic content and antioxidant capacity, while compound-level evaluation highlighted flavan-3-ols as major contributors. These findings identify roots of C. isauricum as a promising source of natural antioxidants. Full article

Rice protein has limited gelation properties, restricting its food applications. This study added four polyphenols—catechin (C), epicatechin (EC), tannic acid (TA), and proanthocyanidins (PC)—to rice protein to investigate their effects on gel rheology, in vitro digestibility, and microstructure. Multi-spectroscopy and molecular docking were used to explore interaction mechanisms. During the temperature sweep (95 °C), PC- and TA-composite gels (GRP-PC, GRP-TA) showed storage moduli slightly higher than the pure rice protein gel (GRP), while GRP-C and GRP-EC (C- and EC-composite gels) were similar to GRP. In frequency sweep (25 °C), GRP had the highest modulus, followed by GRP-PC > GRP-TA > GRP-EC > GRP-C. Polyphenols reduced total digestibility (from 77.4% to 67.6–75.2%). All polyphenol-complexed gels showed markedly improved ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activities. C and EC induced loosely crosslinked microstructures, whereas TA and PC formed sheet-like aggregates. Fluorescence quenching was predominantly static, with quenching rates TA > PC > EC > C. Binding constants followed the same order. Thermodynamic parameters (ΔH > 0, ΔS > 0, ΔG < 0) indicated hydrophobic interactions as the driving force. Molecular docking revealed that PC formed the most hydrogen bonds (8) with rice glutelin, followed by TA (4), C (5), and EC (3). These findings provide data support for designing rice protein-based functional foods. Full article

In this study, the rank of multifaceted activity of catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin-3-gallate (ECG) and epigallocatechin-3-gallate (EGCG) was addressed. Their antioxidant activity was determined by the differential pulse voltammetry (DPV), whereas their ability to inhibit angiotensin-converting enzyme (ACE) activity, acetylcholinesterase activity (AChE), and formation of the advanced glycation end-products (AGEs) was performed in a model system to show their importance against hypertension, Alzheimer-type dementia, and diabetic’s complication, respectively. The order of the antioxidant potential of catechins in comparision to gallic acid (GA) was EGCG > ECG > EC > EGC ≈ C > GA, whereas the order of the ACE inhibitory activity was EGCG > ECG > EGC > EC > C, thus indicating the importance of the structure–activity relationship. The correlation between IC₅₀ for ACE inhibition of catechins and their antioxidant activity had the value r = −0.60. The order of the AChE enzyme inhibitory activity was EGCG ≈ EGC > ECG > EC > C, and the weak positive correlation between IC₅₀ and the first anodic peak potential (E_pa1) values was noted (r = 0.67). The ranking of the anti-AGE activities was EGCG ≈ ECG > EGC > EC > C, and a negative correlation between the inhibitory activity of catechins against AGE formation and their antioxidant activity was r = −0.82, whereas a positive correlation (r = 0.88) was noted between their first anodic peak potential (E_pa1) values. The provided results expand our knowledge on the multifaceted activity of catechins, indicating EGCG and ECG as the most active antioxidants against inhibition of ACE and AChE as well as towards AGE formation. Full article

Fermented Miang (Camellia sinensis var. assamica) serves as a valuable source of bioactive polyphenols and probiotic-associated components. This study characterized the catechin composition of fermented Miang extracts and evaluated their antioxidant capacity and suitability for cosmetic formulations. High-performance liquid chromatography (HPLC) analysis showed that epigallocatechin gallate (EGCG) was the predominant catechin (7.00 ± 0.93 mg/g dry weight), followed by catechin (C), epicatechin (EC), epicatechin gallate (ECG), and epigallocatechin (EGC). The extracts remained physically and chemically stable for at least three months under various storage conditions, with the dried extract form offering advantages for handling and formulation. Fermentation duration significantly influenced phenolic accumulation and antioxidant activity, with four-month fermentation showing the highest activity. Prototype cleansing formulations, including transparent/opaque soap bars, liquid soap, and shampoo containing fermented Miang extract, exhibited acceptable physicochemical characteristics and retained antioxidant function. These findings highlight fermented Miang as a promising natural ingredient for antioxidant and probiotic-inspired cosmetic applications. Full article

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. 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: Obesity is a multifactorial chronic disease resulting from sustained energy imbalance and modulated by environmental and demographic factors, and it is associated with numerous comorbidities. DNA methylation is an epigenetic modification associated with obesity. Modulation of DNA methylation is a viable target for obesity control strategies. The flavanol (-)-epicatechin (EC) exerts beneficial effects in overweight individuals, suggesting that EC may influence gene regulation through signaling pathways and epigenetic mechanisms. We evaluated whether EC modulates obesity-associated DNA methylation changes using complementary in silico, in vitro, and in vivo approaches. Methods. In silico analyses were performed to explore potential EC interactions with the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B. DNMT activity was measured in nuclear extracts of 4T1 cells in the presence of EC. Finally, in a C57BL/6 mouse model of diet- induced obesity, we assessed global DNA methylation and the expression of the DNA methyltransferases, as well as metabolism-related genes; peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc-1α), pyruvate dehydrogenase kinase isozyme 4 (Pdk4), and nuclear factor erythroid 2–related factor 2 (Nrf2) and relative mitochondrial DNA content (mtDNA/nDNA ratio) in visceral adipose tissue (VAT) and skeletal muscle. Results. EC showed stable in silico interactions within catalytic/cofactor-binding regions of DNMTs and inhibited DNMT activity in vitro in a concentration-dependent manner. In vivo, the obesogenic diet reduced global DNA methylation and decreased transcript levels of Dnmt1, Dnmt3a, and Dnmt3b in skeletal muscle and adipose tissue. EC counteracted obesity-associated DNA methylation changes in skeletal muscle, restoring global methylation and Dnmt expression toward control levels, whereas effects in VAT were limited. EC increased mitochondrial DNA content. Discussion. In silico and enzymatic data suggest that EC may bind DNMT active sites and inhibit DNMT activity in a concentration-dependent manner, supporting a role for EC in obesity-related epigenetic remodeling, particularly in skeletal muscle. EC also increased relative mitochondrial DNA content in VAT and skeletal muscle despite no obesogenic diet effect on relative mitochondrial abundance, consistent with favorable mitochondrial modulation. In conclusion, EC is an epigenetic modulator and may have positive effects in obesity related dysfunctional tissues. Full article

Background: In the context of long COVID, persistent fatigue is among the most prevalent symptoms that can develop after SARS-CoV-2 infection. Mitochondrial myopathy and endothelial dysfunction, which are triggers of inflammation, have emerged as prominent causes of long COVID-induced fatigue. Interestingly, the intake of flavanols, particularly (−)-epicatechin (EC), has been associated with the positive modulation of endothelial and mitochondrial structure and function. Methods: In this work, we conducted a randomized, double-blind, placebo-controlled clinical trial to determine whether an EC-enriched supplement (ECES) improves plasma markers of inflammation, endothelial structure, and fatigue-related endpoints in patients with long COVID-19. Results: The study included 46 subjects (mean age 52 years) who were instructed to consume two capsules/day for 90 days of either ECES (n = 23) or placebo (n = 23). Endpoints assessed included mean changes in plasma inflammatory markers (IL-1β, IL-6, and TNF-α) and endothelial dysfunction markers (syndecan-1), handgrip strength, fatigue scale, and quality of life (QoL). The results showed significant improvements in the ECES group for inflammatory markers, syndecan-1, and fatigue compared with the placebo group. Conclusions: The results yield intriguing positive findings for EC and open a new avenue for treating long COVID. Full article

(−)-Epicatechin (EC), taxifolin (Tax), and quercetin (Q) are flavonoids with different C-ring structures. We compared their physicochemical properties and biological activities. The comparison of their stability and redox properties was conducted at mildly acidic or neutral conditions mimicking the plant vacuole or gut, and their sympathetic hyperactivation ability was examined using catecholamine (CA) excretion and blood flow. At pH 5, flavonoids were stable, but at pH 7, their retention rates decreased in the order EC > Q > Tax. LC-MS analysis detected brown oxidized oligomers in EC, while Tax and Q primarily yielded degradation products. All flavonoids exhibited O₂^•− scavenging activity after incubation at pH 5. At pH 7 after 45-min, EC and Tax promoted O₂^•−, while Q only scavenged O₂^•− after 24-hr incubation, EC’s properties decreased but Tax’s properties enhanced. Computational chemistry analysis indicated EC has higher reactivity compared to Tax and Q. EC caused a significant increase in CA excretion and blood flow, which were not observed with Tax or Q or 24-h cultured EC. These results suggest that the C-ring structure of flavonoids plays a crucial role in their stability and redox properties. Furthermore, reactive oxygen species generated by flavonoids in the gut may exert beneficial effects through sympathetic activation. Full article

Background/Objectives: Ochratoxin A (OTA) is a widespread foodborne mycotoxin linked to chronic kidney disease of unknown etiology. Despite evidence from animal models showing OTA accumulation in the kidney, the molecular mechanisms underlying its renal disposition in humans remain only partially understood. Here, we identify human renal transporters responsible for OTA kidney accumulation, elimination, and establish Michaelis–Menten kinetics under matched conditions to directly compare transport mechanisms. We also aim to identify inhibition potential of these transport mechanisms with common dietary polyphenols. Methods: Mammalian cells and membrane vesicles overexpressing human renal transporters were used to screen and profile the uptake and efflux of OTA. Miquelianin, (-)-Epicatechin-3-O-gallate, myricetin, luteolin, and caffeic acid were tested as potential concentration-dependent transporter inhibitors. Results: We demonstrate that OTA is a substrate for human organic anion transporter (hOAT) 1 (K_m: 2.10 ± 0.50 μM, V_max: 396.9 ± 27.0 pmol/mg/min), hOAT3 (K_m: 2.58 ± 0.83 μM, V_max: 141.4 ± 30.3 pmol/mg/min), hOAT4 (K_m: 6.38 ± 1.45 μM, V_max: 96.9 ± 18.8 pmol/mg/min), and human organic anion transporting polypeptide (hOATP) 1A2 (K_m: 37.3 ± 6.2 μM, V_max: 801.0 ± 133.9 pmol/mg/min). Among efflux transporters, OTA was transported only by human breast cancer resistance protein (hBCRP), which has minimal renal expression. While none of the uptake transporters were potently inhibited (>90%) by polyphenols at 10 μM, luteolin inhibited hBCRP-mediated transport of OTA with an IC₅₀ of 22 μM and caffeic acid stimulated hBCRP-mediated efflux with an EC₅₀ of 713.8 μM, both of which are physiologically relevant intestinal lumen concentrations. Conclusions: Our results confirm that exposure to OTA will lead to renal accumulation and increased health risks in affected populations, necessitating increased scrutiny of our food sources. Full article

Epicatechin is a flavonoid of the catechin subclass, found in fruits and medicinal plants such as açaí and green tea, widely studied for its anti-inflammatory properties. However, flavonoids often present chemical instability, low aqueous solubility, and poor bioavailability, limiting their therapeutic potential. This study aimed to incorporate epicatechin into nanocapsules to improve its applicability and evaluate whether the formulation maintains its anti-inflammatory effects via modulation of the NLRP3 inflammasome. Nanocapsules containing 0.25 mg/mL of epicatechin (NC-ECs) were prepared with Eudragit L-100 using interfacial deposition of a preformed polymer. The formulations were characterized for particle size, polydispersity index, zeta potential, and pH, as well as thermal stability over 45 days. Encapsulation efficiency and drug content were determined by high-performance liquid chromatography (HPLC), and morphology analyzed by atomic force microscopy (AFM). Cytocompatibility was assessed in VERO cells, and anti-inflammatory activity was investigated in THP-1-derived macrophages stimulated with LPS + nigericin. The NC-ECs displayed suitable physicochemical properties, high encapsulation efficiency (96%), and full drug loading. The formulation also showed good cytocompatibility and preserved anti-inflammatory activity through NLRP3 inflammasome modulation at low concentrations. These findings indicate NC-ECs as a promising nanotechnological strategy for treating inflammatory diseases involving NLRP3, highlighting its potential contribution to nanomedicine. Full article

Stelechocarpus burahol (kepel) is valued for its aromatic fruits and medicinal leaves, yet its genomic and phytochemical features remain poorly characterized. This study estimated the nuclear DNA content of kepel leaves at 3.96 pg per haploid genome (genome size: 3873 Mbp) and comprehensively profiled their bioactive metabolites. Leaf extracts prepared with water and 70% ethanol, with or without pulsed electric field (PEF) treatment, were analyzed using HPLC-MS, UHPLC-QTOF-MS, HPLC-DAD, and GC-MS. Leaf extracts showed the highest phenolic and flavonoid contents, with PEF markedly improving ethanolic extraction efficiency. A total of 72 phenolics, 2 tocopherols, 3 tocotrienols, and several novel vitamin E derivatives were detected, alongside abundant catechins, tannic acid, and gallic acid. PEF significantly enhanced catechin recovery: catechin (C) increased from 153.7 to 846.8 mg/g and epicatechin (EC) from 338.2 to 921.4 mg/g in water extracts, while ethanolic extracts rose from 335.3 to 905.1 mg/g (C) and 245.0 to 616.9 mg/g (EC). Epigallocatechin 3-gallate (EGCG), absent in untreated leaves, reached 799.9 mg/g in water and 231.9 mg/g in ethanol extracts after PEF. In fruits, PEF reduced phenolic recovery in water extracts (C: 236.7 → 136.8 mg/g; EC: 135.4 → 118.2 mg/g; EGCG: 2892.2 mg/g → undetectable), but slightly improved ethanolic extracts (C: 237.8 → 289.4 mg/g). GC-MS identified 19 volatile compounds contributing to the fruit’s aroma. This work provides the first integrated report of kepel genome size and phytochemical composition, highlighting PEF as a promising strategy to enhance leaf catechin extraction and supporting kepel’s potential as a functional food and medicinal resource. Full article

Chronic inflammation conducts an irreplaceable role in the aging process. More importantly, the impact is particularly significant in scenarios involving cardiac arrest and cardiopulmonary resuscitation (CA/CPR), where elderly individuals are inclined to suffer from more severe inflammatory injuries when compared to younger counterparts. Network pharmacology demonstrated a tight correlation between epicatechin (EC), aging, and the NRG1-NF-κB signaling pathway. With an aim to investigate whether EC suppressing inflammatory aging and alleviating post-CA/CPR brain injury is associated with the inhibition of the NRG1-NF-κB pathway, we established a model of naturally aged 21-month-old rats subjected to CA/CPR. A network pharmacology method was employed to pinpoint possible pathways that connect EC to neuroinflammation associated with aging. Sixty rats were randomly divided into three groups for feeding: a control group (pure water) and EC groups (EC was administered by gavage at doses of 1 mg/kg and 2 mg/kg respectively from the 12th month). Those groups underwent a CA/CPR procedure. At 24-h post-resuscitation, neurological scores, cortical pathology staining and assessments of neural injury were conducted. Expression levels of NRG1-NF-κB pathway-relevant inflammatory factors and proteins underwent systematic investigation by carrying out ELISA, RT-PCR, and Western blotting. In comparison with the 21-month-old groups treated with water, the 21-month-old groups treated with EC at 1 mg/kg and 2 mg/kg demonstrated decreased β-galactosidase staining, aging-correlated proteins and pro-inflammatory factors and NF-κB pathway-relevant proteins, as well as reinforced NRG1-ErbB4 expression. EC lessened inflammatory aging and mitigates post-CA/CPR brain injury in aged rats, associated with the inhibition of the NRG1-NF-κB pathway. Full article