Search Results (145)

Methylglyoxal (MGO) is a highly reactive a-dicarbonyl compound produced in foods and endogenously in humans and constitutes a predominant precursor of advanced glycation end products that contribute to the pathology of several diseases, including diabetes and neurodegenerative diseases. In this study, the efficiency of pyrogallol, gallic acid, ethyl, and propyl gallate in trapping MGO was investigated at pH 6.5 to 8.0. Pyrogallol was the most efficient MGO-trapping agent, followed by gallic acid, whereas the alkyl gallates were notably less efficient, particularly at slightly acidic and neutral pH. The increase of pH from slightly acidic to alkaline enhanced the MGO-trapping efficiency of all compounds, albeit to a different extent that correlated inversely to the pK_a of the most acidic -OH phenolic group, demonstrating the contribution of the deprotonated forms of the phenolic compounds in the enhanced reactivity towards MGO. The reaction products of pyrogallol, identified as the most efficient compound in MGO-trapping, were analyzed and characterized by liquid chromatography-mass spectrometry (LC-MS). Both mono-MGO and di-MGO conjugated adducts of pyrogallol were detected, with the mono-MGO adduct being dominant solely at acidic pH and the di-MGO pyrogallol adducts becoming prevalent at neutral and alkaline pH. Therefore, the pH was determined as a main factor that controls the reaction pathways of the phenolic compounds with MGO. Full article

Harmful α-dicarbonyl compounds (α-DCCs) were formed via Maillard reaction (MR) during the production of seafood condiments. The method of reducing α-DCCs could be achieved through optimizing the MR parameters. In this study, Flounder (Pleuronectiformes) steak was chosen as the raw material for developing seafood condiments with lower α-DCCs using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Indicators such as amino acid nitrogen, peptides, and total antioxidant capacity (T-AOC) of enzymolysis hydrolysates were applied to evaluate the enzymolysis effects on Flounder steak in different protease groups. When optimizing the parameters in MR, an optimal formulation with lower α-DCCs was chosen from the flavourzyme group to prepare Flounder seafood condiment at 105 °C, pH 6.5, 1.5% D-xylose addition, and a 20 min reaction time. The concentrations of methylglyoxal (MGO), glyoxal (GO), 2,3-butanedione (2,3-BD), and 3-deoxyglucosone (3-DG) were reduced to 1.23, 0.23, 0.01, and 0.05 μg/g, respectively, which were lower than those identified in 10 commercial seafood condiments (1.84, 0.39, 0.09, and 0.05 μg/g) and conformed to the standards of daily intake in the United States and the European Union. The quality verification demonstrated that the optimal Flounder seafood condiment had a similar odor profile but with higher intensity than that of the products on the market, which scored 89.79 in sensory evaluation. The results indicated that the process optimized in this study could be applied to prepare a Flounder seafood condiment with lower α-DCCs. This processing technology to control α-DCCs may be employed to improve the quality and safety of foods and contribute to human health. Full article

Glyoxal (GO) is a reactive dicarbonyl derived endogenously from sugars and other metabolic reactions within cells. Numerous exogenous sources of this compound include tobacco smoking, air pollution, and food processing. GO is toxic to cells mainly due to its high levels and reactivity towards proteins, lipids, and nucleic acids. We speculate that glyoxal could be involved in erythrocyte protein damage and lead to cell dysfunction. The osmotic fragility and level of amino and carbonyl groups of membrane proteins of erythrocytes incubated for 24 h with GO were identified. The amount of thiol, amino, and carbonyl groups was also measured in hemolysate proteins after erythrocyte treatment with GO. In hemolysate, the level of glutathione, non-enzymatic antioxidant capacity (NEAC), TBARS, and activity of antioxidant enzymes was also determined. The study’s results indicated that GO increases erythrocyte osmotic sensitivity, alters the levels of glutathione and free functional groups in hemolysate proteins, and modifies the activity of antioxidant enzymes. Our findings indicate that GO is a highly toxic compound to human erythrocytes. Glyoxal at concentrations above 5 mM can cause functional changes in erythrocyte proteins and disrupt the oxidoreductive balance in cells. 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

The dietary intake amount of processing contaminants does not reflect their actual exposure risk due to interactions with the food matrix during gastrointestinal processes, which significantly modulate their bioaccessibility. This study systematically investigated the in vitro digestion patterns of advanced glycation end products (AGEs) and α-dicarbonyl compounds (α-DCs) in biscuits and the modulatory effects of ferulic acid and epicatechin. The results demonstrated that more than 80% of AGEs and α-DCs were present in the bioaccessible fraction of the samples after intestinal digestion. Ferulic acid (FA, 0.05%, w/w) significantly increased the AGEs content in the bioaccessible fraction after intestinal digestion compared to control samples. Conversely, FA at 0.2% and 0.5%, as well as epicatechin (EC) at 0.05%, significantly reduced the glyoxal and 3-deoxyglucosone levels during oral digestion and significantly increased these contaminants contents after gastric digestion. The higher the concentration of EC, the lower the level of methylglyoxal during oral and gastric digestion. In addition, we identified the adducts of FA with lysine and the adducts of EC with Nε-Carboxymethyl-lysine using LC-QTOF-MS, demonstrating the reactivity between polyphenols, amino acids and contaminants. This study provides guidance and suggestions for mitigating dietary exposure to AGEs and α-DCs. Full article

Advanced glycation end products (AGEs) are a series of structurally complex and harmful compounds formed through the reaction between the carbonyl group of reducing sugars (such as glucose and fructose) and the free amino groups of proteins, lipids, or nucleic acids. Excessive accumulation of AGEs in the body can trigger oxidative stress, induce inflammatory responses, and contribute to the development of diabetes, atherosclerosis, and neurological disorders. Within the category of dicarbonyl compounds, methylglyoxal (MGO)—a byproduct resulting from glucose degradation—serves as a pivotal precursor in the formation of AGEs and the induction of neurotoxicity. Specifically, AGEs generated from MGO display significant cytotoxicity toward cells in the central nervous system. Therefore, we aimed to investigate the role of MGO-AGEs in neuroinflammation mediated by CUMS. Interestingly, we found that the overexpression of glyoxalase 1 (GLO1) reduced the levels of MGO in corticosterone-treated microglia, thereby alleviating the inflammatory response. Furthermore, overexpression of GLO1 in the hippocampus of chronically stressed mice reduced MGO levels, mitigating CUMS-induced neuroinflammation and cognitive impairment. Additionally, when using the receptor for advanced glycation end products (RAGE) inhibitor FPS-ZM1 in primary microglia cells, we observed that despite corticosterone-induced elevation of MGO, no significant inflammatory response occurred. This suggests that RAGE clearance can reduce MGO-AGE-mediated neurotoxicity. Subsequently, we used FPS-ZM1 to treat chronically stressed mice and found that it significantly ameliorated neuroinflammation and cognitive dysfunction. These results suggest that targeting MGO metabolism could serve as a therapeutic approach to manage neuroinflammation in stress-related mental disorders. Full article

Background: Italy’s plant biodiversity, characterized by many plant species, is an important source of bioactive secondary metabolites that help reduce the risk of the development of advanced glycation end product (AGE)-related diseases. AGEs are involved in various diseases, such as diabetes, cardiovascular, and neurodegenerative disorders. Therefore, the aim of the study was to investigate the antiglycative, hypoglycemic, and neuroprotective properties of nine edible plant extracts using different in vitro assays. Methods: The ability of the extracts to counteract AGE formation was evaluated at different stages of the glycation reaction using in vitro systems based on the determination of Amadori products and the co-incubation of a model protein with a dicarbonyl compound under different experimental conditions. In addition, the extracts’ methylglyoxal (MGO) and glyoxal (GO) trapping ability was investigated. Hypoglycemic activity was assessed by measuring α-amylase inhibition, while the neuroprotective effects were explored by testing amyloid β peptide 1-42 (Aβ1-42) fibrillogenesis inhibition. Results: All extracts generally had a dose-related capacity for the inhibition of AGE formation, mainly at the intermediate stage of the glycation reaction; high trapping capacity against MGO and GO; and promising hypoglycemic properties. In addition, they affected the fibrillogenesis process by reducing mature amyloid fibril formation and altering fibril morphology. Conclusions: All tested extracts had promising anti-fibrillogenic properties. Rosa canina extract was the most active among the tested plant species given its antiglycative activity (about 80% inhibition of AGE formation), trapping capacity against MGO and GO (almost 100%), hypoglycemic effects (66.20 ± 0.88%), and anti-fibrillogenic effects (69.00 ± 4.49% inhibition), indicating its suitability in the management of AGE-related diseases and for the potential development of a novel food ingredient. Full article

Psoriasis is a multifactorial inflammatory disease. Methylglyoxal (MG) is a highly reactive dicarbonyl compound responsible for dicarbonyl stress in some inflammatory conditions, and it may play a role in the etiopathogenesis of psoriasis. Methods: A total of 50 patients with psoriasis and 35 healthy individuals participated in this study. The following indices were assessed in patients: Body Surface Area (BSA), Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI). MG concentration was evaluated in blood samples. The following inflammatory response indices were calculated: Systemic Inflammation Response Index (SIRI), Systemic Immuno-inflammation Index (SII), and Aggregate Index of Systemic Inflammation (AISI). Results: An analysis of the obtained data showed a statistically significant decrease in the mean serum MG concentration in patients with psoriasis when compared to the healthy individuals (1.19 ± 0.4 μg/mL vs. 1.75 ± 0.6 μg/mL; p = 0.000002). In the patients, MG concentration correlated negatively with psoriasis disease severity indicators (BSA and PASI), C-reactive protein (CRP) concentration, and inflammatory response indicators (SII and AISI). Conclusions: The decreased concentration of MG may be attributed to an increased accumulation of its derivatives (advanced glycation end-products) in the inflamed skin and/or scavenging by polyamines. Full article

Suitable planting systems are critical for the physicochemical and bioactivities of strawberry (Fragaria × ananassa Duch.) polysaccharides (SPs). In this study, SPs were prepared through hot water extraction, and the differences in physicochemical characteristics and bioactivities between SPs derived from elevated matrix soilless planting strawberries (EP-SP) and those from and conventional soil planting strawberries (GP-SP) were investigated. A higher extraction yield was observed for EP-SP (5.88%) than for GP-SP (4.67%), and slightly higher values were measured for the average molecular weight (632.10 kDa vs. 611.88 kDa) and total sugar content (39.38% vs. 34.92%) in EP-SP. In contrast, a higher protein content (2.12% vs. 1.65%) and a more ordered molecular arrangement were exhibited by GP-SP. Monosaccharide composition analysis revealed that EP-SP contained higher levels of rhamnose (12.33%) and glucose (49.29%), whereas GP-SP was richer in galactose (11.06%) and galacturonic acid (19.12%). Thermal analysis indicated only minor differences in decomposition temperatures (approximately 225–226 °C) and thermal stability between the samples. However, GP-SP showed a higher enthalpy change (ΔHg = 18.74 J/g) compared to EP-SP (13.93 J/g). Biological activity assays revealed that GP-SP generally exerted stronger non-enzymatic glycation inhibition at both early and final stages (IC₅₀: 7.47 mg/mL vs. 7.82 mg/mL and 11.18 mg/mL vs. 11.87 mg/mL, respectively), whereas EP-SP was more effective against intermediate α-dicarbonyl compounds (maximum inhibition of 75.32%). Additionally, GP-SP exerted superior α-glucosidase inhibition (IC₅₀ = 2.4583 mg/mL), in line with kinetic and fluorescence quenching analyses showing a higher enzyme–substrate complex binding affinity (Kis = 1.6682 mg/mL; Ka = 5.1352 × 10⁵ M⁻¹). Rheological measurements demonstrated that EP-SP solutions exhibited a pronounced increase in apparent viscosity at higher concentrations (reaching 3477.30 mPa·s at 0.1 s⁻¹ and 70 mg/mL) and a stronger shear-thinning behavior, while GP-SP showed a comparatively lower viscosity and lower network order. These findings suggest that different planting systems significantly affect both the molecular structures and functionalities of SPs, with GP-SP demonstrating enhanced hypoglycemic and anti-glycation properties. It is therefore recommended that suitable planting systems be selected to optimize the functionality of plant-derived polysaccharides for potential applications in the food and pharmaceutical industries. Full article

Liquid and vapor phase transfer hydrogenation with 2-alkanols as hydrogen donors in the presence of MgO as a catalyst was studied. A series of dicarbonyl compounds as well as the equimolar mixtures of various monocarbonyl compounds were used as hydrogen acceptors in order to determine the chemoselectivity (ChS) in the reduction of their carbonyl groups. Thus, 1,4-diacetylbenzene was reduced to 1-(4-acetylphenyl)-1-ethanol with 89% ChS and 1,3-diacetyl-4,6-dimethylbenzene with 100% ChS. Mesitylene diacyl derivatives were unreactive in the studied reaction. CTH of an equimolar mixture of benzaldehyde and acetophenone gave benzyl alcohol and 1-PhEtOH with yields of 91 and 3%, respectively (97% ChS). An equimolar mixture of acetophenone and 6-undecanone underwent CTH with yields of the corresponding alcohols of 89 and 2%, respectively, with 98% ChS towards 1-PhEtOH. Significant differences in reactivity in CTH were reported for an equimolar mixture of regioisomeric 1- and 2-acetylnaphthalenes. The yields of the corresponding alcohols were 20 and 68% with a ChS of 77% towards 2-NphCH(OH)Me. In the case of CTH of 3-oxo-2,2-dimethylbutanal and 2,4-bis(spirocyclohexyl)-1,3-cyclobutanedione with 2-propanol, only the solvolysis of the substrates was observed. The products were methyl isopropyl ketone and isopropyl formate for the former diketone and 1-(cyclohexylcarbonyl)-1-(carboisopropoxy)cyclohexane for the latter. Full article

Gold-catalyzed propargylic substitution of propargylic alcohols 1 with 1,3-dicarbonyl compounds 2 followed by cycloisomerization in ionic liquid enables the environmentally friendly synthesis of polysubstituted furans 3 in good-to-high yields. The reaction proceeds via the hydrated propargylic substitution product 3″aa. The gold catalyst can be recycled at least three times. Full article

Carbonic anhydrases (CAs) are a group of zinc-containing enzymes involved in many physiological processes through their role in the maintenance of the equilibrium between bicarbonate and CO₂ levels. Human carbonic anhydrases (hCAs) are recognized as important drug targets due to their major implication in the development of diseases including cancer. Sulfanilamide derivatives have been widely studied and have shown remarkable efficiency in inhibiting carbonic anhydrases, with the presence of SO₂NH₂ in their structure. Therefore, the sulfonamide moiety is considered as the leading scaffold in the search for new hCA inhibitors. Moreover, the introduction of an enaminone to sulfonamide-based CA inhibitors showed an enhancement of inhibitory activity. In this context, we were interested in the in silico investigation of benzenesulfonamide derivatives containing β-enaminone that were synthesized from dicarbonyl compounds and sulfanilamide under microwave irradiation. The in silico assessment includes a molecular docking simulation against hCA II (PDB: 2AW1). The docked ligands showed good docking score values (−8.099 and −7.053 kcal.mol⁻¹), which indicates a good stability of the studied compounds within the active site. Further, significant interactions with the residues of the active site were observed, including metal coordination with Zn 262, an H-bond with Thr 199, and pi–pi stacking with the side chain of His94, which are considered as the key interactions for CA inhibition. A complementary in silico study that involved ADMET prediction was performed to learn more about the pharmacokinetic properties and the toxicity of the products in order to comprehend their ability to become drug-candidates. Full article

Fluorinated organic compounds have demonstrated remarkable utility in medicinal chemistry due to their enhanced metabolic stability and potent therapeutic efficacy. Several examples exist of fluorinated non-steroidal anti-inflammatory drugs (NSAIDs), including diflunisal, flurbiprofen, and trifluoromethylated pyrazoles celecoxib and mavacoxib. These trifluoromethylated pyrazoles, which are most commonly constructed through the cyclocondensation of a trifluorinated 1,3-dicarbonyl and an aryl hydrazine, are also found in numerous other drug candidates. Here, we interrogate the effects of solvents and the presence of Brønsted or Lewis acid catalysts on catalyzing this process. We highlight the utility of benchtop ¹⁹F NMR spectroscopy in enabling the real-time quantification of reaction progress and the identification of fluorinated species present in crude reaction mixtures without the need for cost-prohibitive deuterated solvents. Ultimately, we find that the reaction solvent has the greatest impact on the rate and product yield, and also found that the relationship between the keto-enol equilibrium of the dicarbonyl starting material pyrazole formation rate is highly solvent-dependent. More broadly, we describe the optimization of the yield and kinetics of trifluoromethylpyrazole formation in the synthesis of celecoxib and mavacoxib, which is made possible through high-throughput reaction screening on benchtop NMR. Full article

Background: Diabetic retinopathy is the most common retinal vascular disease, affecting the retina’s blood vessels and causing chronic inflammation, oxidative stress, and, ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main methylglyoxal (MGO) formation pathway. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the receptor for AGEs (RAGE) pathway. Conclusions: This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed. Full article

This study investigates the palladium-catalyzed one-pot synthesis of functionalized furans from 1,3-Dicarbonyl compounds and alkenyl bromides, focusing on various catalysts and reaction parameters. Different catalysts, including PdCl₂(CH₃CN)₂, Pd(OAc)₂, and Pd(acac)₂ as well as solvents, bases, and oxidants, were systematically evaluated. PdCl₂(CH₃CN)₂ emerged as the most effective catalyst, achieving a remarkable yield of 94%. Optimal reaction conditions were identified as PdCl₂(CH₃CN)₂ in dioxane at 80 °C with K₂CO₃ as the base and CuCl₂ as the oxidant. This study also explored various 1,3-diketones including Cyclohexane-1,3-dione, 5,5-Dimethylcyclohexane-1,3-dione, 2H-Pyran-3,5(4H,6H)-dione, Cyclopentane-1,3-dione, Pentane-2,4-dione, Ethyl 3-oxobutanoate, 1,3-Diphenylpropane-1,3-dione, 1,3-Dip-tolylpropane-1,3-dione, 1,3-Bis(4-chlorophenyl)propane-1,3-dione, and 1,3-Bis(4-bromo- phenyl)propane-1,3-dione, alongside different alkenyl bromides such as allyl bromide, (E)-1-Bromo-3,4-dimethylpent-2-ene, 1-Bromo-3-methylbut-2-ene, 3-Bromocyclohex-1-ene, and (E)-1-Bromohex-2-ene. These variations demonstrated the method’s versatility and the significant impact of substituents on reactivity and reaction yield. These findings highlight the importance of optimizing reaction conditions to maximize efficiency and provide insights into improving catalytic processes for enhanced product yields. Full article