Formation Of End Products Research Articles

Aloin reduces advanced glycation end products, decreases oxidative stress, and enhances structural stability in glycated low-density lipoprotein.

Glycation of proteins has been linked to several cardiovascular diseases, including atherosclerosis and diabetes mellitus. Various natural compounds have been explored for their anti-glycating ability. Aloin is the major anthraquinone glycoside, acquired from the Aloe species. This study focuses on aloin's anti-glycating and anti-oxidative potential on glycated low-density lipoprotein (LDL). Fluorescence studies related to anti-glycation showed that aloin significantly reduced the formation of fluorescent advanced glycation end-products (AGEs), hydrophobic environment, and fibrillar aggregates in glycated LDL. A decrease in oxidative stress markers was also seen in glycated LDL in the presence of aloin. Circular dichroism spectra depicted the positive role aloin played in restoring the secondary structure of LDL. Mode of binding between aloin and LDL were obtained through spectroscopic measurements, which revealed significant binding characteristics. Molecular docking studies confirmed the interaction with a binding energy of -8.5 kcal/mol, indicating a strong affinity between aloin and LDL. Furthermore, the stability of the aloin-LDL complex was validated by molecular dynamics simulations, showing that the secondary structure of LDL remained largely unchanged throughout the simulation period, indicating high stability of the complex. These findings open up new possibilities for using aloin in therapeutic applications aimed at cardiovascular health, potentially leading to the development of novel treatments or preventive measures for atherosclerotic cardiovascular diseases.

ESTRADIOL IMPACTS MÜLLER GLIA AND ENDOTHELIAL CELL RESPONSES IN HYPERGLYCEMIC MICROENVIRONMENTS WITH ADVANCED GLYCATION END PRODUCTS

Diabetic retinopathy is a leading cause of vision loss in working adults, with disproportionate impact on women with lowered estrogen. Sex hormones and their receptors are significant to neuroprotection of the inner blood-retinal barrier (iBRB), a tissue that regulates transport across the neuroretina and vasculature. Moreover, high glucose levels in diabetes lead to the formation of advanced glycation end products (AGEs), which promote inflammation and iBRB breakdown to result in vision loss. This study examined the effects of supplemental estradiol on cell reactivity and cell barrier resistance within an in vitro model of hyperglycemia. Changes in morphology and expression of reactive oxygen species were examined when cells were exposed to a hyperglycemic medium containing AGEs, with and without supplemental estradiol. Cell morphology was assessed via changes in cell area and cell shape index, while intracellular ROS levels were measured using a ROS-sensitive dye. In addition, trans endothelial resistance (TEER) assays were used to measure changes in cell barrier function in response to hyperglycemic conditions, with and without supplemental estradiol. Results show that ROS levels in Müller glia in hyperglycemic conditions significantly decreased in response to supplemental estradiol. The estradiol further increased the resistivity of Müller glia and endothelial cell barriers cultured in high glucose and AGEs. This project illustrates the restorative effects of estradiol in collective responses of cell barriers formed by endothelial cells and Müller glia.

Mitigating methylglyoxal-induced glycation stress: the protective role of iron, copper, and manganese coordination compounds in Saccharomyces cerevisiae.

Glycation-induced stress (G-iS) is a physiological phenomenon that leads to the formation of advanced glycation end-products, triggering detrimental effects such as oxidative stress, inflammation, and damage to intracellular structures, tissues, and organs. This process is particularly relevant because it has been associated with various human pathologies, including cancer, neurodegenerative diseases, and diabetes. As therapeutic alternatives, coordination compounds with antioxidant activity show promising potential due to their versatility in attenuating oxidative stress and inflammation. Herein, we investigated the antioxidant-related protective potential of a series of complexes: [Cu(II)(BMPA)Cl2] (1), [Fe(III)(BMPA)Cl3] (2), and [Cl(BMPA)MnII-(μ-Cl)2-MnII(BMPA)-(μ-Cl)- MnII(BMPA)(Cl)2]•5H2O (3), all synthesized with the ligand bis-(2-pyridylmethyl)amine (BMPA) in Saccharomyces cerevisiae exposed to G-iS caused by methylglyoxal (MG). Pre- treatment with complexes 1-3 proved highly effective, increasing yeast tolerance to G-iS and attenuating mitochondrial dysfunction. This observed phenotype appears to result from a reduction in intracellular oxidation, lipid peroxidation levels, and glycation. Additionally, an increase in the activity of the antioxidant enzymes superoxide dismutase and catalase was observed following treatment with complexes 1-3. Notably, although complexes 1-3 provided significant protection against oxidative stress induced by H2O2 and menadione, their protective role was more effective against MG-induced glycation stress. Our results indicate that these complexes possess both antiglycation and antioxidant properties, warranting further investigation as potential interventions for mitigating glycation and oxidative stress-related pathologies.

Cutaneous Carbonyl Stress Is Associated With Nerve Dysfunction in Recent-Onset Type 2 Diabetes.

Endogenous carbonyl stress leads to the formation of advanced glycation end products (AGEs). AGEs represent a potential target to prevent or treat diabetic sensorimotor polyneuropathy (DSPN). The current study aimed to characterize cutaneous carbonyl stress, oxidative stress, immune cells, and endothelial cell damage in early type 2 diabetes compared with normal glucose tolerance (NGT) using novel cutaneous biomarkers. Included were 160 individuals recently (≤12 months) diagnosed with type 2 diabetes and 144 with NGT from the German Diabetes Study baseline cohort. Nerve function was assessed using electrophysiological, quantitative sensory, and clinical testing. Skin biopsies were obtained to analyze intraepidermal nerve fiber density, AGEs autofluorescence, argpyrimidine area, and endothelial cell area. In addition, skin autofluorescence was measured noninvasively using the AGE reader. A subgroup with type 2 diabetes (n = 80) was reassessed 5 years later. After adjustment for sex, age, HbA1c, LDL cholesterol, and BMI, argpyrimidine area (17.5 ± 18.8 vs. 11.7 ± 12.7%) was higher in recent-onset type 2 diabetes than in NGT (P < 0.05). AGEs autofluorescence was inversely correlated with nerve conduction (e.g., peroneal motor nerve conduction velocity: r = -0.346) and positively with AGE reader measurements in type 2 diabetes (r = 0.358, all P < 0.05), but not in NGT. Higher baseline AGEs autofluorescence and lower endothelial cell area predicted the deterioration of clinical and neurophysiological measures after 5 years. Cutaneous AGEs markers were associated with neurophysiological deficits in recent-onset type 2 diabetes and predicted their progression after 5 years, substantiating the role of carbonyl stress in the development of early DSPN.

Advanced glycation end-products accelerate amyloid deposits in adipocyte's lipid droplets.

Adipose tissue dysfunction is central to insulin resistance, and the emergence of type 2 diabetes (T2D) is associated with elevated levels of carbonyl metabolites from glucose metabolism. In this study, using methylglyoxal (MGO) and glycolaldehyde (GAD) carbonyl metabolites induced protein glycation, leading to misfolding and β-sheet formation and generation of advanced glycation end products (AGEs). The formed AGEs compromise adipocytes activity. Microscopic and spectroscopic assays were used to examine the impact of MGO and GAD on lipid droplet-associated proteins. The results provide information about how these conditions lead to the appearance of glycated and amyloidogenic proteins formation that hinders metabolism and autophagy in adipocytes. We measured the beneficial effects of metformin (MET), an anti-diabetic drug, on misfolded protein as assessed by thioflavin (ThT) spectroscopy and improved autophagy, determined by LC3 staining. In vitro findings were complemented by in vivo analysis of white adipose tissue (WAT), where lipid droplet-associated β-amyloid deposits were predominantly linked to adipose triglyceride lipase (ATGL), a lipid droplet protein. Bioinformatics, imaging, biochemical and MS/MS methods affirm ATGL's glycation and its role in β-sheet secondary structure formation. Our results highlighted the pronounced presence of amyloidogenic proteins in adipocytes treated with carbonyl compounds, potentially reshaping our understanding of adipocyte altered activity in the context of T2D. This in-depth exploration offers novel perspectives on related pathophysiology and underscores the potential of adipocytes as pivotal therapeutic targets, bridging T2D, amyloidosis, protein glycation, and adipocyte malfunction.

Antioxidant Potential and In Vitro Antidiabetic Activity of Paeonia japonica (Makino) Miyabe &amp; Takeda Extract and Its Isolated Compounds

This study explored the potential of Paeonia japonica (Makino) Miyabe &amp; Takeda (P. japonica) as a natural treatment for diabetes. A methanol extract of the root of P. japonica and its fractions were investigated for their antioxidant and antidiabetic properties. The ethyl acetate (EtOAc) fraction was the most potent, displaying strong antioxidant activity and inhibiting enzymes that break down carbohydrates (α-amylase and α-glucosidase), which could reduce blood sugar levels. Furthermore, the EtOAc fraction inhibited glucose uptake in 3T3-L1 cells and stimulated the gene responsible for cellular glucose uptake (GLUT4), suggesting improved insulin sensitivity. It also effectively reduced the formation of harmful advanced glycation end products linked to diabetic complications. The isolation of bioactive compounds from the EtOAc fraction revealed the presence of 4-O-methylgallic acid and ellagic acid, which potentially contributed to the observed antidiabetic effects. Overall, this study highlights the EtOAc fraction of P. japonica as a promising source for developing natural diabetes therapies. The findings suggest its potential for regulating various diabetic pathways, warranting further research for drug development.

Exploring the role of the TLR4/NF-B signaling pathway in diabetic retinopathy

Abstract. Diabetes mellitus (DM) is a major cause of blindness and the neurodegenerative and microvascular disease known as diabetic retinopathy (DR). Diabetes-related retinal neurodegeneration (DRN) is thought to be a potential therapeutic target for primary or secondary prevention of traditional DR while the exact nature of the link between DRN and diabetic retinal vasculopathy (DRV) is still unknown. Therefore, compared with the DRV, in-depth study of DRN may provide a better understanding of this important cause of blindness. Immunoinflammatory mechanisms are currently believed to play crucial role in the occurrence and development of DR. Interrelated molecular pathways, such as the formation of glycosylation end products and oxidative stress (OS) in late diabetes, contribute to the inflammatory response. Furthermore, blocking the TLR4/NF-B signaling pathway has been shown to be an effective way to reduce DR, as demonstrated by a number of studies. This paper examines the function of the inflammatory response and TLR4/NF-B signaling pathway in the pathophysiology of DRN, which may offer fresh perspectives on DR therapy.

ANTIOXIDANT, INHIBITION OF ADVANCED GLYCATION END-PRODUCT FORMATION AND ANTIMICROBIAL ACTIVITIES OF OCIMUM GRATISSIMUM (SCENT LEAF) METHANOLIC LEAF EXTRACT AGAINST Escherichia coli AND Bacillus SPP

The study investigates the antioxidant, inhibition of advanced glycation end-product formation and antimicrobial activities of methanolic leaf extract of Ocimum gratissimum. GC-MS, qualitative, antioxidant scavenging and antiglycation activities of the extract of Ocimum gratissimum were determined using standard procedures. The antimicrobial activity was evaluated by agar well diffusion method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using standard methods. The GC-MS analysis of Ocimum gratissimum leaf revealed the presence of 49 compounds with P –cymene been the most abundant. The phytochemical screening of the extract shows the presence of alkaloids, tannins, phenolic, flavonoids, saponins etc. The in-vitro antioxidant assay of the extract was found to have ?-carotene, lycopene, total phenolic compounds, total flavonoid compounds, reducing power and DPPH scavenging activities. The extract showed significant inhibitory effects on the formation of compounds containing two carbonyl groups and Advanced Glycated End products formation with IC50 of 75.85 ±4.87 µg/mL. Agar well diffusion assay was characterized by inhibition zones of 21.0 ± 0.30, 19.66 ± 0.20, 33.78± 0.30 and 33.25 ± 0.40 mm for Escherichia coli and Bacillus spp respectively at 250 mg/ml for Ocimum gratissimum and 25 mg/ml for tetracycline solution. The MIC values for E.coli and Bacillus spp were 33.33, 66.67, 0.78 and 0.78 for both extract and tetracycline while their MBC values were 66.67, 133.00, 1.56 and 1.56 respectively. MBC/ MIC values showed that Ocimum gratissimum extract and tetracycline had bactericidal effects. These results indicated that Ocimum gratissimum possesses antioxidant, prevents glycation and has antimicrobial activities.

Health Benefits of Olive Leaf: The Focus on Efficacy of Antiglycation Mechanisms.

Olive leaves have been a therapeutic herbal agent for diseases for centuries. Olive leaves contain many health-beneficial nutrients and bioactive components. There is much evidence for the positive effects of the phenolic compounds they contain on health. The main active phenolic component in olive leaves is oleuropein, which can constitute 6%-9% of the leaf's dry matter and has been intensively studied for its promising results/effects on human health. In addition, olive leaf provides health benefits through bioactive components, such as secoiridoids, flavonoids, triterpenes, and lignans. The anti-inflammatory, antioxidant, anticancer, antidiabetic, and antihypertensive properties of bioactive components, especially oleuropein, are well known. In addition, various health benefits, such as neuroprotective effects and microbiota modulation, are also mentioned. In recent years, in vitro studies have shown that olive leaves and bioactive components from olive leaves may have antiglycation effects. Currently, it is thought that the components found in olive leaves have a direct or indirect antiglycation effect. It is thought that, their direct effects include reducing the interaction between sugars and amino acids, nucleic acids, and lipids and sequestering reactive dicarbonyl species, and their indirect effects include preventing the formation of advanced glycation end-products (AGEs) by reducing inflammation and oxidative stress. However, in vivo and clinical studies are needed to prove these mechanisms and understand how their metabolism works in the human body. This review examines the beneficial health effects of olive leaves and their potential antiglycation role.

Insights into Protein and Amino Acid Metabolism of Thermoanaerobacter mathranii

Few investigations have been carried out into the members of the genus Thermoanerobacter for protein and amino acid metabolism compared to carbohydrates, mostly due to the intense interest in bioethanol and biohydrogen in recent decades. The present study investigates the biotechnological potential of Thermoanaerobacter mathranii (DSM 11426) in terms of its ability to produce high-energy alcohols from amino and fatty acids. End product formation from glucose (in the presence and absence of butyrate) as well as from selected proteins and amino acids were analyzed. T. mathranii did not degrade any of the proteins tested to a large extent but degraded several amino acids, namely serine and the branched-chain amino acids (leucine, isoleucine, valine) when cultivated in the presence of thiosulfate. The main end products from the branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols, with the strain producing a concentration of the corresponding branched-chain alcohol between 1.0 and 1.7 mM and 8.2–10.9 mM of the corresponding fatty acid. 13C2-labeled leucine revealed that the strains degraded the amino acid in the presence of thiosulfate, producing 3-methyl-1-butyrate, which was then used as an electron acceptor which led to the accumulation of 3-methyl-1-butanol. The strain is highly ethanologenic, producing more than 1.2 mol of ethanol per mol of glucose degraded. The strain was able to reduce volatile fatty acids during glucose fermentation to their corresponding alcohol, further suggesting this strain may be of greater biotechnological value beyond bioethanol production.

Formation of advanced glycation end products in glucose-amino acid models of Maillard reaction under dry- and wet-heating conditions.

Advanced glycation end products (AGEs) are compounds formed by non-enzymatic processes in the Maillard reaction and can cause various chronic diseases. This study explores the AGE formation process in a glucose-amino acid system under both wet- and dry-heating conditions, and analyzes the effect of cysteine in AGE formation. Under wet-heating conditions, Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) concentrations rose for the initial 90 min and subsequently declined after 120 min; after 90 min of heating, the maximum yields in the absence of cysteine were 1151.04 ± 14.01 and 3386.90 ± 26.55 ng mL-1, respectively. The concentration of pyrraline (Pyr) increased after 30 min and then decreased after 60 min with a maximum yield of 777.68 ± 23.36 ng mL-1. However, in dry-heating models, the AGE concentrations consistently increased with increasing heating time; the maximum yields for CML, CEL and Pyr were 468.66 ± 10.96, 1993.57 ± 14.81 and 1085.74 ± 58.06 ng mL-1, respectively. The addition of cysteine showed an inhibitory effect on AGE formation, especially for Pyr in the dry-heating model, with inhibition rates ranging from 17.14% to 95.60%. Although wet-heating models produced more CML and CEL, they produced less Pyr than dry-heating models. The AGE formation in wet-heating models positively correlated with the reaction rate; however, the dry-heating reaction demonstrated a more complex relationship between reaction rate and reaction protocol. Moreover, cysteine exhibited a significant inhibitory effect on AGE production, and the degree of inhibition was proportional to the cysteine concentration. This study provides important insights into the mechanisms for AGE formation under various heating conditions, such as those representing baking (dry-heating) and steaming conditions (wet-heating). © 2024 Society of Chemical Industry.

Exploring the Functional Potential of Breast Milk Protein Hydrolysates: Antiglycation, Antioxidant, Metal Chelation, and Lipid Peroxidation Activities

The formation of advanced glycation end products (AGEs) is a pivotal factor in the development of various age-related and diabetes associated pathophysiologies, including but not limeted to arthritis, Alzheimer’s disease, atherosclerosis and cataracts. Consequently, the prospect of inhibiting AGE formation emerges as a viable strategy to prevent or halt the advancement of diabetic complications. In the scientific literature, there is still a reluctance to produce bioactive peptides demonstrating antiglycation activity from breast milk. The breast milk protein was hydrolysed using trypsin for 240 min. The antiglycation, metal chelating activity, lipid peroxidation activity, and antioxidant activity of the peptides in the hydrolysates obtained after hydrolysis of human milk with trypsin enzyme were performed. The peptide diversity obtained after hydrolysis was determined by RP-HPLC. The breast milk hydrolysate was demonstrated significant antiglycation activity (IC50: 312.8 ± 12.1 µg/mL), antioxidant activity (61.8±4.58 mM AAE/µg peptide) , metal chelation activity (24.4%/μg peptide). The hydrolysate effectively inhibited lipid peroxidation (30.5±0.12%) compared to Trolox (51.2±0.3%). These findings highlight the potential of breast milk protein hydrolysates as a source of bioactive peptides with diverse health benefits. The present study offers valuable insights into utilizing human milk peptides as novel functional food components.

Quantitative and Rapid In Vivo Imaging of Human Lenticular Fluorescence.

To quantitatively investigate the chemical origins of near-UV excited fluorescence in the crystalline lens, and demonstrate the potential usefulness of a rapid and noninvasive diagnostic approach for screening and monitoring of lens damage. Anterior segment UV fluorescence imaging was applied to a population of 30 healthy adults, ages 18 to 64 years. Absolute fluorescence intensities and intensity ratios were compared across the population as a function of age. Fluorescence quantum yield (FQY) was calculated from imaging results based on a previous radiometric characterization. Typical FQYs at 365nm excitation are approximately 0.2% for healthy adults. Intensity and FQY were observed to increase significantly with age, consistent with ex vivo and confocal microscopy studies. The ratio of blue to green fluorescence is strongly correlated with FQY and age, suggesting that both increases in fluorophore concentration and changes in composition occur with age. Fluorescence data is quantitatively and qualitatively consistent with pyridine nucleotides in young adults, and changes with age are consistent with formation of β-carbolines or advanced glycation end products. Intralens variation is consistent with increased oxidation or glycation in the lens nucleus relative to the cortex. Lenticular fluorescence can be measured rapidly, accurately, and quantitatively in vivo which provides a spatially resolved, quantitative measure of lens chemistry, including damage from oxidation and glycation. Careful interpretation of fluorescence intensities and intensity ratios can provide chemical insight into lens health. Anterior segment UV fluorescence imaging can thus serve as a useful tool for screening, monitoring, and research of lens damage and cataract formation.

Formation of amino acid–based imidazole salts considerably increased the determined level of fluorescent advanced glycation end products in biscuits

Glycine, serine, and γ-aminobutyric acid are effective scavengers of reactive carbonyl species and should inhibit the formation of advanced glycation end products (AGEs). However, here we found that amino acids unexpectedly increased the intensity of fluorescent AGEs in biscuits. This study aimed to elucidate these contradictory findings and highlight concerns regarding the determination of fluorescent AGEs in foods. In gliadin-methylglyoxal (MGO) glycation model, amino acids were found to induce formaldehyde formation from MGO. Thereafter, formaldehyde and MGO reacted with the amino acids to generate imidazole salts. The imidazole salts exhibited broad fluorescence range, overlapping with the fluorescence range used to determine fluorescent AGEs in foods, thus resulting in an apparent increase in fluorescent AGEs content after amino acid addition. Since amino acids are ubiquitous in food materials, the formation of imidazole salts during food processing may result in an overestimation of fluorescent AGEs in foods.

Methylglyoxal alters collagen fibril nanostiffness and surface potential

Collagen fibrils are fundamental to the mechanical strength and function of biological tissues. However, they are susceptible to changes from non-enzymatic glycation, resulting in the formation of advanced glycation end-products (AGEs) that are not reversible. AGEs accumulate with aging and disease and can adversely impact tissue mechanics and cell-ECM interactions. AGE-crosslinks have been related, on the one hand, to dysregulation of collagen fibril stiffness and damage and, on the other hand, to altered collagen net surface charge as well as impaired cell recognition sites. While prior studies using Kelvin probe force microscopy (KPFM) have shown the effect glycation has on collagen fibril surface potential (i.e., net charge), the combined effect on individual and isolated collagen fibril mechanics, hydration, and surface potential has not been documented. Here, we explore how methylglyoxal (MGO) treatment affects the mechanics and surface potential of individual and isolated collagen fibrils by utilizing atomic force microscopy (AFM) nanoindentation and KPFM. Our results reveal that MGO treatment significantly increases nanostiffness, alters surface potential, and modifies hydration characteristics at the collagen fibril level. These findings underscore the critical impact of AGEs on collagen fibril physicochemical properties, offering insights into pathophysiological mechanical and biochemical alterations with implications for cell mechanotransduction during aging and in diabetes. Statement of SignificanceCollagen fibrils are susceptible to glycation, the irreversible reaction of amino acids with sugars. Glycation affects the mechanical properties and surface chemistry of collagen fibrils with adverse alterations in biological tissue mechanics and cell-ECM interactions. Current research on glycation, at the level of individual collagen fibrils, is sparse and has focused either on collagen fibril mechanics, with contradicting evidence, or surface potential. Here, we utilized a multimodal approach combining Kelvin probe force (KPFM) and atomic force microscopy (AFM) to examine how methylglyoxal glycation induces structural, mechanical, and surface potential changes on the same individual and isolated collagen fibrils. This approach helps inform structure-function relationships at the level of individual collagen fibrils.

Facile fabrication of redox nanoparticles loaded with exosomal-miRNAs and resveratrol as glycation inhibitor in alleviating the progression and development of diabetic cataract.

Diabetic cataract (DC) represents a highly prevalent ocular manifestation resulting from diabetes often culminating in vision impairment among individuals with diabetes. Regrettably, the armamentarium of pharmaceutical interventions capable of both delaying and thwarting the onset of DC remains conspicuously sparse. Based on contemporary investigations, the pathogenesis of DC is prominently influenced by oxidative harm to the crystalline lens and the nonenzymatic glycosylation of lens proteins. Consequently, we have developed self-regenerating cerium oxide nanoparticles (CeO2 NPs), enveloped with resveratrol (RSV) and exosomal-microRNA (miRNA) to alleviate the effects of DC in an in vitro model. Moreover, the inclusion of RSV within CeO2 NPs serves a dual purpose. It can act as an antioxidant, minimizing glycation, and induce oxidative stress by effectively neutralizing reactive oxygen species (ROS). Additionally, it serves as a glycation inhibitor effectively preventing the cross-linking. Consequently, it helps minimize the glucose level in hemoglobin and inhibits the formation of advanced glycation end products (AGEs). Likewise, the CeO2-exosomal-miRNA when treated alone found to slightly impede the viability of human lens epithelial cells (HLEC) and induce apoptosis by suppressing the expression of α-crystalline gene (CRYAA). Particularly, miRNAs target genes associated with oxidative stress pathways, protein glycation, and the generation of AGEs, hence preventing structural damage to lens proteins. Compared with CeO2, RSV-CeO2, and miRNA-RSV-CeO2, the presence of miRNA-RSV-CeO2 led to a significant decrease in hemoglobin glycation. Remarkably, miRNA-RSV-CeO2 NPs attenuate the formation of malondialdehyde (MDA) and conjugated dienes (CD) with a relative value of 14.63 and 11.37nmol/mg. As per the report, this method presents a promising opportunity to implement the proposed material combination for attenuating diabetic cataracts.

Plasma-activated water pretreatment as a promising technique to reduce the formation of heterocyclic aromatic amines and advanced glycation end products in roasted fish patties

This study investigated the efficacy of using plasma-activated water (PAW) as a novel and additive-free pretreatment in reducing the formation of free and bound heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) in roasted fish patties. PAW activated for different durations (50 s, 100 s, and 150 s), significantly decreased the levels of HAAs and AGEs. The highest inhibition rates were observed at 35.44% and 19.82% for free and bound HAAs, respectively, and 42.76% and 23.23% for free and bound AGEs, respectively. PAW pretreatment reduced the formation of HAAs and AGEs and mitigated their increase during storage. Analysis using electron paramagnetic resonance and UPLC-MS/MS showed a decrease in free radicals and reactive carbonyls (phenylglyoxal, glyoxal, and methylglyoxal), which can serve as intermediates for HAAs and AGEs. Correlation analysis indicated a significant positive correlation between HAAs/AGEs and phenylacetaldehyde, glyoxal, methylglyoxal, and the total spin number (P < 0.05). This suggests that PAW suppresses the production of reactive carbonyls by quenching free radicals, thereby inhibiting the formation of HAAs and AGEs. In conclusion, with its additive-free approach, PAW pretreatment holds promise for reducing HAAs and AGEs and improving the safety of roasted fish products.

Inhibitory effect of caffeic acid and dihydrocaffeic acid on the formation of advanced glycation end products: Mechanism analysis based on intermolecular interaction

The accumulation of advanced glycation end products (AGEs) generated from glycation reaction accelerates the development and deterioration of some diseases. Herein, the AGEs model of fructose-induced glycation of human serum albumin (HSA) was constructed and characterized. Both caffeic acid (CA) and dihydrocaffeic acid (DHCA) can inhibit the formation of AGEs, and the inhibitory effect of CA was more pronounced, as confirmed by fluorescence spectroscopy, gel electrophoresis, scanning electron microscopy, and carbonyl and thiol contents analysis. The binding of CA and DHCA to HSA was investigated by fluorescence spectroscopy and molecular docking. The primary inhibitory mechanism was the occupation of the glycation site LYS199 of HSA, and the more significant inhibitory effect of CA was related to its stronger binding affinity. Furthermore, the conformational changes caused by glycation and CA/DHCA binding were monitored using fluorescence, circular dichroism, and dynamic light scattering analysis. The results would help to elucidate the inhibitory mechanism of CA and DHCA on AGEs formation based on their different structures and inhibitory effects, and provide guidance for choosing natural inhibitors for diabetes.

Increased Levels of Circulating Methylglyoxal Have No Consequence for Cerebral Microvascular Integrity and Cognitive Function in Young Healthy Mice.

Diabetes and other age-related diseases are associated with an increased risk of cognitive impairment, but the underlying mechanisms remain poorly understood. Methylglyoxal (MGO), a by-product of glycolysis and a major precursor in the formation of advanced glycation end-products (AGEs), is increased in individuals with diabetes and other age-related diseases and is associated with microvascular dysfunction. We now investigated whether increased levels of circulating MGO can lead to cerebral microvascular dysfunction, blood-brain barrier (BBB) dysfunction, and cognitive impairment. Mice were supplemented or not with 50mM MGO in drinking water for 13weeks. Plasma and cortical MGO and MGO-derived AGEs were measured with UPLC-MS/MS. Peripheral and cerebral microvascular integrity and inflammation were investigated. Cerebral blood flow and neurovascular coupling were investigated with laser speckle contrast imaging, and cognitive tests were performed. We found a 2-fold increase in plasma MGO and an increase in MGO-derived AGEs in plasma and cortex. Increased plasma MGO did not lead to cerebral microvascular dysfunction, inflammation, or cognitive decline. This study shows that increased concentrations of plasma MGO are not associated with cerebral microvascular dysfunction and cognitive impairment in healthy mice. Future research should focus on the role of endogenously formed MGO in cognitive impairment.

Enrichment of shortcrust pastry cookies with bee products: polyphenol profile, in vitro bioactive potential, heat-induced compounds content, colour parameters and sensory changes

Bee products, including bee pollen (BP) and bee bread (BB) are natural sources that contain a diverse range of bioactive compounds. The objective of this study was to investigate the potential of BP and BB to enhance the functional properties of shortcrust pastry cookies. The impact on BP and BB on the colour parameters, polyphenolic compounds content, heat-induced compounds content (acrylamide, furfural, 5-hydroxymethylfurfural (HMF)), antioxidant properties, and inhibitory effects against advanced glycation end products (AGEs) formation and acetylcholinesterase (AChE) activity was examine by enriching cookies with 3 and 10% of BP or BB. The incorporation of BP or BB resulted in a notable darkening of the cookies. The spectroscopic and chromatographic analyses revealed that the cookies enriched with bee products exhibited an elevated content of phenolic compounds. The antioxidant activity (AA) of the enriched cookies exhibited an average increase of 2- to 3-fold in the ABTS test and 2-fold in the DPPH test. All cookies exhibited inhibitory potential against AGEs formation, witch inhibitory rates ranging from 10.64 to 46.22% in the BSA-GLU model and 1.75–19.33% in BSA-MGO model. The cookies enriched with 10% BP were characterised by to the highest level of AChE activity inhibition (13.72%). The incorporation of BB and BP resulted in elevated concentration of acrylamide, furfural, and HMF. Our findings suggest that bee products may serve as a valuable addition to food ingredients, significantly enhancing the functional properties of shortcrust pastry cookies. However, further investigation is necessary to address the increased level of heat-induced compounds.