Moderate red wine consumption has been associated with cardioprotective effects, which have been partly attributed to its polyphenolic content. However, human intervention studies remain limited, particularly regarding polyphenol-enriched wines with reduced alcohol content. In this study, we have formulated and characterized a non-fermented grape skins polyphenol-enriched (GSPE) red wine reduced in alcohol, and its effects were evaluated in a randomized, double-blind intervention comparing GSPE wine with a reduced-alcohol control red wine on metabolic and antioxidant-related biomarkers in overweight adults or individuals presenting components of the metabolic syndrome. After a three-week alcohol washout period, participants were randomly assigned to consume either GSPE wine (n = 21) or control wine (n = 22) daily for 5-6 weeks. Anthropometric parameters, blood pressure, antioxidant levels, and biochemical markers were assessed at baseline and at the end of the intervention. Consumption of the GSPE wine resulted in a significant reduction (p < 0.05) in serum alanine aminotransferase levels compared with baseline and relative to the control group, with no adverse changes in other hepatic parameters. In contrast, control wine showed a significant increase in plasma uric acid levels and total antioxidant activity, together with a slight but significant decrease in albumin concentration (p = 0.03). These parameters were not significantly altered following GSPE wine intake. Taken together, these findings suggest that polyphenol-enriched wine may attenuate alcohol-associated alterations in hepatic biomarkers.

(Poly)phenols can prevent protein glycation by trapping reactive dicarbonyl compounds. However, the extent to which thermal treatment (TT) alters their capacity to preserve cellular proteostasis under methylglyoxal (MG) stress remains poorly understood. In this study we assessed how TT (90 degrees C, 1 h) and solvent extraction modulate the antiglycation and proteostasis-related activities of (poly)phenol-enriched extracts (PEEs) from the Chilean currant Ribes magellanicum. Raw and TT PEEs were obtained using ethanol:acetic acid (99:1), ethanol:water: acetic acid (75:24:1), or ethanol:water:acetic acid (50:49:1), and characterized by HPLC-DAD, cyclic voltammetry, and UHPLC-QTOF-MS/MS, together with antioxidant and MG-trapping assays. In human gastric epithelial (AGS) cells, PEEs were evaluated for their ability to modulate cell viability, protein glycation and carbonylation, and proteasome activity under MG-induced stress. PEEs-TT showed lower antioxidant capacity and MG-trapping efficiency than raw PEEs. Nevertheless, cellular outcomes were strongly dependent on extraction solvent. Notably, only raw PEEs obtained with ethanol:acetic acid (99:1) preserved chymotrypsin-like proteasome activity and also attenuated protein glycation and carbonylation in AGS cells. Uptake experiments in an intestinal epithelial model revealed marked structure- and solvent-dependent differences in anthocyanin cellular incorporation, highlighting processing-dependent changes in phenolic availability. Collectively, these results demonstrate that TT induces oxidative and chemical modifications of R. magellanicum (poly)phenols that diminish their chemical reactivity towards MG while preserving their capacity to maintain cellular proteostasis under MG-induced stress, through combined effects on phenolic availability, MG trapping, and activation of intracellular antioxidant defense pathways, providing mechanistic insight into how food processing modulates the biological activity of berry (poly)phenols.

The objective of this study was to obtain and characterize bioactive peptides derived from common bean (Phaseolus vulgaris) landraces and to evaluate their antioxidant potential using multiple in vitro assays. Protein isolates were obtained by isoelectric precipitation followed by enzymatic hydrolysis using Alcalase. Peptides were separated by ultrafiltration into fractions < 3 kDa and 3-10 kDa, yielding a total of forty samples. Antioxidant activity was evaluated using DPPH, FRAP, and ORAC assays. Antioxidant responses ranged from 13.06 to 50.8% inhibition in DPPH, 52.2 to 1750 µmol TE/100 g in FRAP, and 305 to 5246 µmol TE/100 g in ORAC. Resistance against oxidation ranged from 10.6 to 68.8%. Peptides < 3 kDa generally exhibited higher antioxidant activity in the functional assays, particularly in the Apolo, Magnum, Boloto, and Hallado landraces, although some 3-10 kDa fractions also showed relevant activity. Peptide extraction yields ranged from 3.73 to 10.39% and from 1.33 to 4.74%, while soluble protein contents ranged from 23.1 to 460 and from 9.9 to 288 mg BSA/100 g beans for <3 kDa and 3-10 kDa fractions, respectively. Overall, the results support the potential of common bean-derived peptides as functional food ingredients with antioxidant activity mediated through multiple mechanisms.

Frailty syndrome (FS) is a critical factor associated with several oxidative stress and age-related diseases. In this work, we investigated the connection between frailty, defined at early stages using a new cut-off value of the Frailty Trait Scale (FTS-5), and plasma biomarkers of oxidative stress. Plasma samples of 76 older women were analyzed to determine free and protein-bounded tryptophan (Trp), kynurenine (Kyn), N-formylKynurenine (N-Kyn), advanced glycation end products, and protein carbonylation. A subgroup of 30 subjects was selected from the entire group to determine malondialdehyde (MDA), free methionine (Met), phenylalanine (Phe), Trp, and Kyn. In the whole group (N = 76), Kyn and the Kyn/Trp ratio were higher in women with a Romberg test altered (p-values = 0.0439, and 0.0472, respectively) and BMI < 25.3 kg/m2 (p-values = 0.0008, and 0.0011, respectively). Increased protein carbonylation was found for subjects with BMI ≥ 25.3 kg/m2. For the subgroup, an increase in the Kyn/Trp ratio was observed in subjects with an altered Romberg test, concomitant with decreased levels of Trp, Met, Phe, and MDA (p-values = 0.0255, 0.0427, 0.0459, and 0.0173, respectively) when data were grouped according to the modified FTS-5. These results highlight the relevance of oxidative biomarkers as a tool for an early diagnosis of FS and its related complications.

Los productos finales de glicación avanzada (AGEs, por sus siglas en inglés) constituyen un grupo heterogéneo de moléculas provenientes de reacciones no enzimáticas que ocurren principalmente entre proteínas y azúcares reductores. Su origen en el organismo es endógeno o exógeno (dieta). La ingestión de alimentos con un alto contenido de AGEs incrementa sus niveles en el plasma, lo que se asocia con estrés oxidativo, inflamación y, a largo plazo, con el desarrollo de diversas patologías crónicas asociadas al envejecimiento, como las cardiometabólicas, la diabetes mellitus tipo 2 y la demencia. Por el contrario, las dietas con un bajo contenido de estas glicotoxinas se han asociado a menor riesgo de estas patologías, con reducción de los niveles de estrés oxidativo y glicoxidativo. En consecuencia, resulta importante reconocer estrategias orientadas a reducir los niveles de AGEs alimentarios, especialmente en las personas mayores, debido a que los cambios fisiológicos asociados al envejecimiento aumentan su labilidad al efecto del consumo de estas glicotoxinas. En esta revisión narrativa se describen brevemente algunas consecuencias metabólicas del consumo de AGEs, así como diversas formas de reducir su contenido en los alimentos, principalmente a través de modificaciones fisicoquímicas, tales como el control del pH, de la temperatura y de la actividad de agua, así como el empleo de polifenoles, de bayas nativas chilenas, como agentes inhibidores de su formación.

Advanced glycation end products (AGEs) are irreversible products formed when long-lived proteins undergo non-enzymatic reactions with reducing sugars or reactive metabolites. These products resist proteolytic degradation and therefore accumulate with age. Some AGEs act as chromophores, absorbing UVA-visible light and initiating photosensitized oxidation, a process implicated in photoaging of tissues such as the eye lens and skin. Dietary polyphenols, known for their antioxidant and antiglycation effects, may also modulate AGE-mediated photosensitized reactions, although this remains poorly understood. This article discusses the mechanisms through which AGEs contribute to photo-oxidative damage in light-exposed tissues and discusses the potential of dietary polyphenols to modulate these photo-induced processes.

Phenolic compounds have antiglycation activity, but the changes occurring during thermal treatment (TT) in these activities are not completely understood. The effects of the extraction conditions of (poly)phenols from Ribes magellanicum fruits, before and after TT, on their antioxidant and antiglycation effects were assessed. (Poly)phenol-enriched extracts (PEEs) from raw and TT (90 °C, 1 h) Ribes magellanicum were extracted using three solvent mixtures (ethanol/water/acetic acid) with increasing water content (0, 24, and 49%) and three solvent-to-solid ratios (5, 10, and 20 mL/g). PEEs of raw samples showed increased values of total (poly)phenols (TPC), TEAC, and FRAP and decreased IC50 values of fluorescent advanced glycation end products (AGEs) with increasing water content. An increase in TPC and FRAP values was observed for TT samples, but an increase in the IC50 values of fluorescent AGEs for PEEs with increasing water content was observed. Antiglycation activity (IC50 raw/IC50 TT) depended on the solvent-to-solid ratio and the extracting solvent. HPLC-DAD-MS analysis of raw and TT samples showed degradation of anthocyanins, flavonoid fragmentation, and oxidation as the main changes in the phenolic composition of TT samples. We show that TT affects the (poly)phenolic composition of R. magellanicum, producing a decrease in the antiglycation activity when extractions are performed with increasing water content, despite increasing TPC and FRAP activity.

Diabetes is a chronic metabolic disorder with systemic complications. Hyperglycemia damages multiple organs, including the brain, increasing the risks of stroke, dementia, and oxidative stress. Diabetes is also linked to ventricular enlargement in the human brain. Here, we examine how diabetes alters the secretion of subcommissural organ spondin (SCO-spondin) and Wnt5a by SCO cells, which subsequently affects ependymal ciliary beating and cerebrospinal fluid (CSF) circulation. Under diabetic conditions, SCO-spondin secretion by SCO cells increased. CSF-borne SCO-spondin was observed interacting with ependymal cilia, which showed increased stiffness. Control SCO cells were Wnt5a-positive, indicating active biosynthesis and secretion; in contrast, Wnt5a immunostaining was negative under diabetic conditions, and its interaction with ependymal cells decreased. Additionally, the Wnt5a receptor Frizzled-2 and the proteoglycan testican, essential for Wnt5a-receptor engagement, were not detected in ependymal cells during diabetes. To further explore downstream changes, we examined aquaporin-4 (AQP4) in control and diabetic samples and found condition-dependent differences in its subcellular distribution within ependymal cells. Accordingly, peri-ependymal edema and periventricular lucency were observed. Conversely, GLUT1, MCT2, and Cx-43 remained unchanged, suggesting that diabetes selectively modifies specific ependymal properties. Proteomic analysis of CSF from diabetic patients confirmed the presence of spondin-1 and thrombospondins, which may replace SCO-spondin in humans. Overall, these findings support a model where increased SCO-spondin release and decreased Wnt5a-Frizzled-2-testican signaling in ependymal cells promote ciliary stiffening and periventricular edema in the diabetic brain.

Advanced glycation end products (AGEs) are a heterogeneous group of molecules resulting from non-enzymatic reactions that occur primarily between proteins and reducing sugars. The intake of foods with a high AGEs content, increases their levels in plasma, which is associated with oxidative stress, inflammation, and long-term, the development of various age-related chronic pathologies, such as cardiometabolic diseases, type 2 diabetes mellitus, and dementia. On the contrary, diets with a low content of these glycotoxins have been associated with a lower risk of these pathologies, with reduced levels of oxidative and glycoxidative stress. Consequently, it is important to recognize strategies aimed at reducing the levels of AGEs in foods, especially in the elderly, due to the physiological changes due to the aging process, which makes them more susceptible to cardiometabolic and other diseases. This narrative review briefly describes some effects of the consumption of AGEs, as well as various ways to reduce their content in food, mainly based on physicochemical changes such as pH, temperature, and water activity control, as well as the use of polyphenols, from Chilean native berries, as inhibitors of their formation.

Advanced glycation end products (AGEs) are a heterogeneous group of compounds formed during the advanced stages of the Maillard reaction through non-enzymatic reactions, occurring mainly between reducing sugars or their oxidation metabolites and amino groups in proteins, lipids, and nucleic acids. These compounds can be endogenously formed, particularly under hyperglycemic conditions. In addition, AGEs are also produced exogenously during the thermal processing of foods, contributing to the dietary intake of these compounds. The accumulation of AGEs in body tissues has been associated with aging and the pathogenesis of various non-communicable diseases. Dietary intake of AGEs contributes significantly to their systemic burden. Consequently, reducing the intake of dietary AGEs has been proposed as a modifiable risk factor for the prevention of chronic, age-related diseases. This review examines and discusses current evidence on the molecular mechanisms by which dietary and endogenous AGEs contribute to cellular senescence and the progression of prevalent age-associated pathologies, including diabetes, cardiovascular diseases, musculoskeletal disorders, and neurodegeneration.

SCOPE:We report a nutritional intervention involving supplementation with boiled beans and secondary metabolites-enriched extracts (SMEEs) from a Chilean Phaseolus vulgaris landrace in mice with induced metabolic syndrome (MS). METHODS AND RESULTS:The effects of supplementation were assessed in C57BL6 mice with MS induced by a high-fat diet. Boiled beans (75 and 150 mg animal day-1) and the SMEE (0.8 and 8 mg animal day-1) were administered daily for 4 months. Weight and glycemia were measured weekly. At the end of the experiment, glycemia, total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, protein carbonyls, and carboxymethyl lysine (CML) levels were determined in plasma. Oral intake of the SMEE decreased glycemia at the end of the intervention. No statistically significant difference in glycemia was found for the boiled beans compared with controls. The SMEE at 0.8 mg animal day-1 decreased the total amount of CML, mainly in proteins with molecular masses >75 kDa, in agreement with the results for carbonylated proteins. CONCLUSION:The SMEE of Peumo beans reduces glycemia at the end of the intervention and decreases total CML in plasma, suggesting a potential beneficial effect of bean intake. The results obtained in the intervention encourage further studies in Chilean bean landraces.

The Chilean papaya (Vasconcellea pubescens A.DC.) is a climacteric fruit that grows in the north and center of Chile. During its processing, residues formed mainly by mucilage and seeds are produced and mostly discarded, despite being a potential source of bioactive metabolites. This work aimed to apply untargeted metabolic analysis by HPLC-DAD-QToF to study the chemical composition of ethyl acetate and methanol extracts from Chilean papaya residues and evaluate their antioxidant and antiglycation capacities. Twenty-three metabolites were tentatively identified in papaya residues, including one carboxylic acid, one glycosylated hydroquinone, four flavan-3-ols, three proanthocyanidins, twelve glycosylated flavonols, one carbohydrate, and one alkaloid reported for the first time. The antioxidant capacity measured as the scavenging of DPPH• and ABTS•+ radicals was comparable with that of ascorbic acid. Chilean papaya extracts decreased fluorescent Advanced Glycation End (AGE) products and oxidative modifications in proteins induced by glucose.

The influence of oxygen on the thermal treatment (TT) of secondary metabolite-enriched extracts (SMEEs) from Tórtola beans and procyanidin C1 (PC1) on the inhibition of advanced glycation end products (AGEs) generation in proteins was investigated. SMEE was incubated at 4 °C (control) or thermally treated at 60 °C for 2 h, at either 0 % O2 (I) or 20 % O2 (II). Treatments I and II increased the content of procyanidin dimers B2. Treatment II was more effective than the control or treatment I in preventing homocysteine oxidation and AGEs generation. TT of PC1 at 0 % or 20 % O2 generated procyanidin dimers and tetramers. PC1 TT at 20 % O2 exhibited higher oxidation potentials and lower IC50 values of fluorescent AGEs than those of controls or TT at 0 % O2. These findings indicate that SMEE from Tórtola beans after treatment II changes the degree of polymerization and oxidation procyanidins, thereby increasing their antiglycation activity.

Olive oil consumption has increased in the last two decades and consequently, its wastes have increased, which generates a tremendous environmental impact. Among the by-products are the olive mill leaves, which are easier and inexpensive to treat than other olive by-products. However, little research has been done on their chemical composition and potential bioactivity. Hence, in this study, olive mill leaves were used to obtain Oleuropein-Enriched Extracts (OLEU-EE) using Conventional Extraction, Ultrasound-Assisted Extraction, and Homogenization-Assisted Extraction. These three techniques were evaluated using a Factorial Design to determine the parameters to obtain an OLEU-EE with high contents of Total Phenolic Compounds (TPC), Antioxidant Activity (AA), and Oleuropein concentration (OLEU). From the results, the Homogenizer-Assisted Extraction (HAE) technique was selected at 18,000 rpm, solid:liquid ratio 1:10, and 30 s of homogenization with 70% ethanol, due to its high TPC (5,196 mg GA/100 g), AA (57,867 μmol of TE/100 g), and OLEU (4,345 mg of OLEU/100 g). In addition, the antiglycating effect of OLEU-EE on the levels of (1) fluorescent Advanced Glycation End Products (AGEs) were IC50 of 0.1899 and 0.1697 mg/mL for 1λEXC 325/λEM 440 and 2λEXC 389/λEM 443, respectively; (2) protein oxidative damage markers such as dityrosine (DiTyr), N-formylkynurenine (N-formyl Kyn), and kynurenine (Kyn) were IC50 of 0.1852, 0.2044, and 0.1720 mg/mL, respectively. In conclusion, OLEU-EE from olive mill leaves has different capacities to inhibit AGEs evidenced by the IC50 of fluorescent AGEs and protein oxidation products, together with the scavenging free radical evidenced by the concentration of Trolox Equivalent. Therefore, OLEU-EE could be potential functional ingredients that prevent oxidative damage caused by free radicals and AGEs accumulation.

Glycoxidative stress with the consequent generation of advanced glycation end products has been implied in the etiology of numerous non-communicable chronic diseases. During the postprandial state, the levels of 1,2-dicarbonyl compounds can increase, depending on numerous factors, including characteristics of the subjects mainly related to glucose metabolism disorders and nutritional status, as well as properties related to the chemical composition of meals, including macronutrient composition and the presence of dietary bioactive molecules and macromolecules. In this review, we examine the chemical, biochemical, and physiological pathways that contribute to postprandial generation of 1,2-dicarbonyl compounds. The modulation of postprandial 1,2-dicarbonyl compounds is discussed in terms of biochemical pathways regulating the levels of these compounds, as well as the effect of phenolic compounds, dietary fiber, and dietary patterns, such as Mediterranean and Western diets.