Search Results (52)

Annurca apple extract is gaining growing attention for its beneficial properties, particularly its outstanding antioxidant activity. Using a combination of biophysical, cell, and molecular biology techniques, this study investigates the sustainable valorization of Annurca apple by-products at different ripening stages and their role in the formation of advanced glycation end-products (AGEs), as well as in protection against AGE-related cytotoxicity. AGEs are a class of compounds formed by non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. They can be produced endogenously or ingested through dietary sources and tobacco smoke. AGEs accumulate in nearly all mammalian tissues and are linked to various health issues, such as diabetes and its related complications, cardiovascular disease, and neurodegenerative disorders. Our data show that Annurca apple by-products at different ripening stages differentially counteract AGEs’ formation by inhibiting protein glycation and protect against AGE-induced cytotoxicity in endothelial cells. In particular, the extracts reduce AGE-induced reactive oxygen species (ROS) production, thereby inhibiting MAPK signaling pathways and caspase-3 activation. Moreover, ripening significantly enhances the concentration of bioactive compounds and the extent of cellular protection. This study highlights new beneficial properties of Annurca apple extracts and suggests that adopting nutritional interventions may support health and potentially reduce the risk of complications associated with AGE accumulation. Full article

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by distinctive chronic cutaneous manifestations. Although immune-mediated and microvascular mechanisms are well established, the role of metabolic dysfunction, particularly hyperglycemia, is underexplored in dermatological conditions. This review synthesizes mechanistic, clinical, and translational evidence to explore the relationship between dysglycemia and cutaneous disease severity in DM. Hyperglycemia is associated with oxidative stress, advanced glycation end-product formation, endothelial injury, and proinflammatory cytokine signaling. These processes may plausibly amplify DM-associated vasculopathy, impair wound healing, and worsen cutaneous inflammation. Limited DM-specific studies demonstrate increased insulin resistance and a higher prevalence of diabetes compared with healthy controls. Meanwhile, case reports suggest that poor glycemic control can exacerbate cutaneous disease. Evidence from other inflammatory dermatoses supports a biologically plausible role for dysglycemia in increasing flare frequency, infection risk, and delayed tissue repair. Dietary patterns characterized by high glycemic index and coexisting metabolic syndrome may further intensify systemic and cutaneous inflammation. Collectively, these findings suggest hyperglycemia as a biologically plausible contributor to cutaneous disease severity in DM that warrants further investigation. These observations highlight the need for future studies to evaluate whether metabolic screening, dietary patterns, and interdisciplinary care influence cutaneous disease activity and wound healing in DM. Prospective clinical investigation is needed to determine whether targeted glycemic optimization is associated with changes in cutaneous and systemic outcomes in DM. Full article

Frozen shoulder (FS), traditionally regarded as an idiopathic musculoskeletal disorder characterized by pain, stiffness, and capsular fibrosis, is increasingly recognized as the clinical manifestation of systemic endocrine, metabolic, vascular, and immunological dysfunctions. This narrative review reframes FS within a broader neuro–endocrine–immunometabolic model, emphasizing the central role of estrogen deficiency, resistance, and receptor-level disruption, together with their interactions with thyroid dysfunction, endothelial health, and lifestyle-related low-grade inflammation (LGI). Evidence from epidemiological, clinical, and mechanistic studies shows that estrogen signaling failure weakens anti-inflammatory, antifibrotic, and antioxidant defenses, predisposing peri- and postmenopausal women to more severe FS phenotypes. Thyroid dysfunction, particularly hypothyroidism, further contributes to fibrosis and pain sensitization. Endothelial dysfunction—driven by poor diet, advanced glycation end-products (AGEs), and oxidative stress—impairs vascular integrity and promotes local microvascular inflammation. In parallel, lifestyle factors such as sedentarism, circadian misalignment, psychosocial stress, and environmental exposures sustain systemic LGI and hormonal resistance. Together, these interconnected mechanisms suggest that FS is not merely a localized joint pathology but a systemic disorder requiring integrative clinical strategies that combine orthopedic management with endocrine evaluation, metabolic monitoring, dietary interventions, circadian health, and stress regulation. In addition, this review outlines specific clinical implications, highlighting how an integrative, personalized approach that targets hormonal, metabolic, vascular, and lifestyle dimensions may improve pain, function, and long-term prognosis in FS. This paradigm shift underscores the need for future research to focus on stratified patient profiling and interventional trials targeting hormonal, vascular, and lifestyle axes to improve outcomes, particularly in women who remain disproportionately affected by FS. Full article

Oral mucositis (stomatitis) is a painful condition that affects the mouth lining. Kampo medicines (e.g., Hangeshashinto [Chinese name, Ban-Xia-Xie-Xin-Tang], Orento, and Orengedokuto) have been widely used to treat stomatitis, such as gargling with Hangeshashinto. However, the mechanisms by which Kampo medicines work are not widely understood due to their oral administration and the subsequent digestion, absorption, and metabolization of their components. Stomatitis is associated with advanced glycation end-products (AGEs) in patients with lifestyle diseases, and can be induced by both intra- and extracellular AGEs (blood and dietary AGEs). Various natural products inhibit intracellular AGE generation and suppress cytotoxicity, such as inflammation caused by extracellular AGEs. This review summarizes 19 natural products identified in the Hangeshashinto water extract and 16 natural products identified in the crude drug extract. The data show that several natural products, such as glycyrrhizin, baicalin, 6-shogaol, quercetin, epigallocatechin-3-galate, and genistein, inhibit intracellular AGEs and suppress extracellular AGE inflammation. Furthermore, several natural products in the Hangeshashito water extract can suppress cytotoxicity in stomatitis. Full article

Dietary advanced glycation end-products (dAGEs) contained in high-sugar/fat and ultra-processed foods of the “Western diet” (WD) pattern predispose to several diseases by altering protein function or increasing oxidative stress and inflammation via RAGE (receptor for advanced glycation end-products). Although elevated endogenous AGEs are associated with loss of muscle mass and functionality (i.e., muscle wasting; MW), the impact of dAGEs on MW has not been elucidated. Here, we show that the most common dAGEs or their precursor, methylglyoxal (MGO), induce C2C12 myotube atrophy as endogenous AGE-derived BSA. ROS production, mitochondrial dysfunction, mitophagy, ubiquitin–proteasome activation, and inhibition of myogenic potential are common atrophying mechanisms used by MGO and AGE-BSA. Although of different origins, ROS are mainly responsible for AGE-induced myotube atrophy. However, while AGE-BSA activates the RAGE-myogenin axis, reduces anabolic mTOR, and causes mitochondrial damage, MGO induces glycolytic stress and STAT3 activation without affecting RAGE expression. Among thirty selected natural compounds, Vaccinium macrocarpon (VM), Camellia sinensis, and chlorophyll showed a surprising ability in counteracting in vitro AGE formation. However, only the standardized VM, containing anti-glycative metabolites as revealed by UHPLC-HRMS analysis, abrogates AGE-induced myotube atrophy. Collectively, our data suggest that WD-linked dAGE consumption predisposes to MW, which might be restricted by VM food supplements. Full article

When breastfeeding is not possible, infant formulas may be used instead of human milk. However, harmful advanced glycation end-products (AGEs) may be formed during thermal processing of infant formulas. The exposure to AGEs at such an early age can lead to chronic diseases in the future. Therefore, the aim of this study was to develop a sensitive method to determine the content of AGEs in infant formulas. Twenty commercial infant formulas (initial and follow-on) in liquid and powder form were investigated using liquid chromatography with tandem mass spectrometry (LC-MS/MS) with a multistep sample pretreatment procedure. Five selected glycation products were analyzed: N^ε-carboxyethyllysine (CEL), N^ε-carboxymethyllysine (CML), furosine, glyoxal lysine dimer (GOLD), and methylglyoxal lysine dimer (MOLD). The mean contents of the tested glycation products did not differ significantly between the initial and follow-on formulas. No significant differences were found in the concentrations of the analyzed compounds from different manufacturers. However, the liquid formulas contained significantly more CML. The estimated dietary exposure to the tested compounds was in the range of 42.5–92.6 μg/day, except for furosine (almost 2 mg/day). The developed method enabled the determination of selected AGEs in complex matrices such as infant formulas. Consumption of liquid infant formulas can result in higher exposure to some AGEs. Full article

Background: Methylglyoxal (MGO), a reactive dicarbonyl compound, has been implicated in the formation of advanced glycation end-products (AGEs) and neuronal dysfunction. This study investigated the neuroprotective effects of the combination of trans-resveratrol and hesperidin (tRES-HESP) against MGO-induced neurotoxicity, focusing on memory dysfunction and depression-like behavior. Methods: Neuroblastoma 2a (N2a) cells were treated with MGO to induce neurotoxicity. The effects of tRES-HESP on cell viability, reactive oxygen species (ROS) production, apoptotic markers (BAX/Bcl 2 ratio, caspase 3 activity, and poly [ADP ribose] polymerase cleavage), and components of the glyoxalase system (glyoxalase-1, glyoxalase- 2, and receptors for AGEs) were assessed. The activation of the Kelch-like ECH-associated protein 1/Nuclear factor erythroid-2-related factor 2/Heme oxygenase-1 (Keap1/Nrf2/HO-1) pathway was also evaluated. In vivo, mice with MGO-induced depressive amnesia were treated with tRES-HESP (200 mg/kg) for eight weeks, and behavioral, biochemical, and histological assessments were performed. Results: tRES-HESP significantly reduced MGO-induced cytotoxicity, ROS production, and apoptosis in N2a cells. In addition, it restored the glyoxalase system and activated the Keap1/Nrf2/HO-1 pathway. In an in vivo model, tRES-HESP improved memory and depression-like behaviors, reduced cortisol and interleukin (IL)-6 levels, increased IL-10 levels, and lowered the expression of amyloid precursor protein and amyloid beta. Furthermore, tRES-HESP protected CA2/3 hippocampal subregions from MGO-induced damage. tRES-HESP exhibited neuroprotective effects through antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. Conclusions: Our results suggest that tRES-HESP is a potential dietary supplement for preventing cognitive decline and depression, particularly in neurodegenerative conditions such as Alzheimer’s disease. Further studies are required to assess its clinical relevance and efficacy in the human population. Full article

Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in cosmetology and dermatology. The primary goal of this review is to understand the significance of glycation-induced skin aging and to examine the therapeutic potential of glycation-targeting strategies. This study covers experimental and clinical studies exploring various interventions to attenuate glycation-induced skin aging. Glycation stress decreases the viability of cells in culture media, the cell-mediated contraction of collagen lattices in reconstructed skin models, and the expression of fibrillin-1 at the dermo-epidermal junction in the skin explants. It also increases cross-links in tail tendon collagen in animals, prolonging its breakdown time. However, these changes are attenuated by several synthetic and natural agents. Animal and clinical studies have shown that dietary or topical administration of agents with antiglycation or antioxidant activity can attenuate changes in AGE levels (measured by skin autofluorescence) and skin aging parameters (e.g., skin color, wrinkles, elasticity, hydration, dermal density) induced by chronological aging, diabetes, high-carbohydrate diets, ultraviolet radiation, or oxidative stress. Therefore, the accumulating experimental and clinical evidence supports that dietary supplements or topical formulations containing one or more synthetic and natural antiglycation agents may help mitigate skin aging induced by AGEs. Full article

Advanced Glycation End Products (AGEs) are formed through non-enzymatic reactions between reducing sugars and proteins, nucleic acids or lipids (for example through hyperoxidation). In diabetes, elevated glucose levels provide more substrate for AGEs formation. AGEs can also be ingested through the diet from foods cooked at high temperatures, or containing much sugar. The present work aimed to review all published randomized controlled trials (RCT) on low-dietary AGE (L-dAGEs) interventions in patients with diabetes. Pubmed, Scopus and Cochrane databases were searched (until 29 February 2024) with appropriate keywords (inclusion criteria: RCT, patients with diabetes, age > 18 years, outcomes related to inflammation, glucose, and lipids; exclusion criteria: non-RCTs, case-series, case reports and Letter to the Editor, or animal studies). The present review was registered to the Open Science Framework (OSF). From 7091 studies, seven were ultimately included. Bias was assessed with the updated Cochrane Risk of Bias tool. A reduction in circulating AGEs was documented in 3/3 studies. No particular differences were documented in glycemic parameters after a L-dAGEs diet. Reductions in glucose levels were observed in one out of six studies (1/6), while HbA1c and HOMA did not change in any study (0/6 and 0/3, correspondingly). Lipid profile also changed in one out of four studies (1/4). More consistent results were observed for oxidative stress (beneficial effects in 3/3 studies) and inflammatory markers (beneficial effects in 4/4 studies). Other athero-protective effects, such as adiponectin increases, were reported. Limitations included the small sample size and the fact that dietary and physical activity habits were not considered in most studies. In conclusion, a L-dAGEs pattern may minimize AGEs accumulation and have beneficial effects on oxidative stress and inflammation indices, while its effects on glycemic and lipemic parameters are inconsistent and modest in patients with diabetes. Full article

Glycation Stress (GS), induced by advanced glycation end-products (AGEs), significantly impacts aging processes. This study introduces a new model of GS of Caenorhabditis elegans by feeding them Escherichia coli OP50 cultured in a glucose-enriched medium, which better simulates human dietary glycation compared to previous single protein–glucose cross-linking methods. Utilizing WormCNN, a deep learning model, we assessed the health status and calculated the Healthy Aging Index (HAI) of worms with or without GS. Our results demonstrated accelerated aging in the GS group, evidenced by increased autofluorescence and altered gene expression of key aging regulators, daf-2 and daf-16. Additionally, we observed elevated pharyngeal pumping rates in AGEs-fed worms, suggesting an addictive response similar to human dietary patterns. This study highlights the profound effects of GS on worm aging and underscores the critical role of computer vision in accurately assessing health status and aiding in the establishment of disease models. The findings provide insights into glycation-induced aging and offer a comprehensive approach to studying the effects of dietary glycation on aging processes. Full article

Red yeast rice dietary supplements have been proven to ameliorate hyperglycemia, but the mechanism was unclear. In this work, ankaflavin (AK) and monascin (MS), as typical pigments derived from red yeast rice, were found to exert noteworthy inhibitory ability against α-glucosidase, with an IC₅₀ of 126.5 ± 2.5 and 302.6 ± 2.5 μM, respectively, compared with acarbose (IC₅₀ = 341.3 ± 13.6 μM). They also exhibited mixed-type inhibition of α-glucosidase in vitro and caused fluorescence quenching through the static-quenching process. Molecular-docking studies indicated that AK and MS bind to amino acid residues outside the catalytic center, which induces structural changes in the enzyme, thus influencing its catalytic activity. The anti-glycation ability of Monascus-fermented products was evaluated, and they exhibited a high inhibition rate of 87.1% in fluorescent advanced glycation end-product formation at a concentration of 0.2 mg mL⁻¹, while aminoguanidine showed a rate of 75.7% at the same concentration. These results will be significant in broadening the application scope of Monascus pigments, especially AK and MS, in treating type 2 diabetes. Full article

Diabetes mellitus (DM), due to its long-term hyperglycemia, leads to the accumulation of advanced glycation end-products (AGEs), especially in the vessel walls. Skin autofluorescence (SAF) is a non-invasive tool that measures AGEs. DM patients have a rich dietary source in AGEs, associated with high oxidative stress and long-term inflammation. AGEs represent a cardiovascular (CV) risk factor, and they are linked with CV events. Our objective was to assess whether SAF predicts future CV events (CVE) by examining its association with other CV risk factors in patients with type 2 DM (T2DM). Additionally, we assessed the strengths and limitations of SAF as a predictive tool for CVE. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we conducted a systematic review with CRD42024507397 protocol, focused on AGEs, T2DM, SAF, and CV risk. We identified seven studies from 2014 to 2024 that predominantly used the AGE Reader Diagnostic Optic tool. The collective number of patients involved is 8934, with an average age of 63. So, SAF is a valuable, non-invasive marker for evaluating CV risk in T2DM patients. It stands out as a CV risk factor associated independently with CVE. SAF levels are influenced by prolonged hyperglycemia, lifestyle, aging, and other chronic diseases such as depression, and it can be used as a predictive tool for CVE. Full article

Diets with an elevated content of fat, sucrose, or fructose are recognized models of diet-induced metabolic alterations, since they induce metabolic derangements, oxidative stress, and chronic low-grade inflammation associated with local and systemic accumulation of advanced glycation end-products (AGEs). This study used four-week-old C57BL/6 male mice, randomly assigned to three experimental dietary regimens: standard diet (SD), high-fat high-sucrose diet (HFHS), or high fructose diet (HFr), administered for 12 weeks. Plasma, heart, and tibialis anterior (TA) skeletal muscle were assayed for markers of metabolic conditions, inflammation, presence of AGEs, and mitochondrial involvement. The HFHS diet induced a tissue-specific differential response featuring (1) a remarkable adaptation of the heart to HFHS-induced heavy oxidative stress, demonstrated by an increased presence of AGEs and reduced mitochondrial biogenesis, and efficaciously counteracted by a conspicuous increase in mitochondrial fission and PRXIII expression; (2) the absence of TA adaptation to HFHS, revealed by a heavy reduction in mitochondrial biogenesis, not counteracted by an increase in fission and PRXIII expression. HFr-induced mild oxidative stress elicited tissue-specific responses, featuring (1) a decrease in mitochondrial biogenesis in the heart, likely counteracted by a tendency for increased fission and (2) a mild reduction in mitochondrial biogenesis in TA, likely counteracted by a tendency for increased fusion, showing the adaptability of both tissues to the diet. Full article

Precursors of advanced glycation endproducts, namely, reactive carbonyl species (RCSs), are aging biomarkers that contribute to cell death. However, the impact of RCSs on ferroptosis—an iron-dependent form of cell death—in skin cells remains unknown. Herein, we constructed a cellular model (with human keratinocyte; HaCaT cells) to evaluate the cytotoxicity of the combinations of RCSs (including glyoxal; GO and methyglyoxal; MGO) and erastin (a ferroptosis inducer) using bioassays (measuring cellular lipid peroxidation and iron content) and proteomics with sequential window acquisition of all theoretical mass spectra. Additionally, a data-independent acquisition approach was used to characterize RCSs’ and erastin’s molecular network including genes, canonical pathways, and upstream regulators. Using this model, we evaluated the cytoprotective effects of two dietary flavonoids including cannflavins A and B against RCSs and erastin-induced cytotoxicity in HaCaT cells. Cannflavins A and B (at 0.625 to 20 µM) inhibited ferroptosis by restoring the cell viability (by 56.6–78.6% and 63.8–81.1%) and suppressing cellular lipid peroxidation (by 42.3–70.2% and 28.8–63.6%), respectively. They also alleviated GO + erastin- or MGO + erastin-induced cytotoxicity by 62.2–67.6% and 56.1–69.3%, and 35.6–54.5% and 33.8–62.0%, respectively. Mechanistic studies supported that the cytoprotective effects of cannflavins A and B are associated with their antioxidant activities including free radical scavenging capacity and an inhibitory effect on glycation. This is the first study showing that cannflavins A and B protect human keratinocytes from RCSs + erastin-induced cytotoxicity, which supports their potential applications as dietary interventions for aging-related skin conditions. Full article

Hormone-related cancers, namely breast, endometrial, cervical, prostate, testicular, and thyroid, constitute a specific group of cancers dependent on hormone levels that play an essential role in cancer growth. In addition to the traditional risk factors, diet seems to be an important environmental factor that partially explains the steadily increased prevalence of this group of cancer. The composition of food, the dietary patterns, the endocrine-disrupting chemicals, and the way of food processing and preparation related to dietary advanced glycation end-product formation are all related to cancer. However, it remains unclear which specific dietary components mediate this relationship. Carbohydrates seem to be a risk factor for cancer in general and hormone-related cancers, in particular, with a difference between simple and complex carbohydrates. Glycemic index and glycemic load estimates reflect the effect of dietary carbohydrates on postprandial glucose concentrations. Several studies have investigated the relationship between the dietary glycemic index and glycemic load estimates with the natural course of cancer and, more specifically, hormone-related cancers. High glycemic index and glycemic load diets are associated with cancer development and worse prognosis, partially explained by the adverse effects on insulin metabolism, causing hyperinsulinemia and insulin resistance, and also by inflammation and oxidative stress induction. Herein, we review the existing data on the effect of diets focusing on the glycemic index and glycemic load estimates on hormone-related cancers. Full article