Formation Of Advanced Glycation End Products Research Articles

β-alanine scavenging of free radicals protects mitochondrial function and enhances both insulin secretion and glucose uptake in cells under metabolic stress

Type 2 diabetes is a disease characterized by dysregulation of glucose homeostasis, with numerous diabetic complications attributable to the resulting chronic exposure of cells and tissues to elevated concentrations of glucose and fatty acids. This in part results from formation of advanced glycation end-products and advanced lipidation end-products that can form adducts with proteins, lipids, or DNA and disrupt their normal cellular function. There is, however, growing evidence that supplementation with the endogenous histidine-containing dipeptide, carnosine, or its rate-limiting precursor, β-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and related conditions. Here we investigated the scavenging potential of β-alanine in INS-1 pancreatic β-cells and C2C12 skeletal muscle myotubes, and show a significant reduction of >60% in reactive species that were generated by glucolipotoxic metabolic stress in both cell types following incubation with β-alanine for 5 days. Furthermore, β-alanine supplementation resulted in a protective action that helped prevent the damaging action of metabolic stress that otherwise leads to inhibition of mitochondrial function in both cell types. This in turn resulted in >60% preservation of insulin secretion and glucose uptake, in INS-1 cells and C2C12 cells respectively, which would otherwise be inhibited by metabolic stress. This suggests potential therapeutic benefit to taking β-alanine supplements as an alternative to carnosine.

Accumulation of Advanced Glycation End-Products in the Body and Dietary Habits.

The formation of advanced glycation end-products (AGE) in tissues is a physiological process; however, excessive production and storage are pathological and lead to inflammation. A sedentary lifestyle, hypercaloric and high-fructose diet and increased intake of processed food elements contribute to excessive production of compounds, which are created in the non-enzymatic multi-stage glycation process. The AGE’s sources can be endogenous and exogenous, mainly due to processing food at high temperatures and low moisture, including grilling, roasting, and frying. Accumulation of AGE increases oxidative stress and initiates various disorders, leading to the progression of atherosclerosis, cardiovascular disease, diabetes and their complications. Inborn defensive mechanisms, recovery systems, and exogenous antioxidants (including polyphenols) protect from excessive AGE accumulation. Additionally, numerous products have anti-glycation properties, occurring mainly in fruits, vegetables, herbs, and spices. It confirms the role of diet in the prevention of civilization diseases.

In vitro evaluation of the anti-diabetic potential of soymilk yogurt and identification of inhibitory compounds on the formation of advanced glycation end-products

In this study, we aimed to identify starter strains of lactic acid bacteria (LAB) to produce soymilk yogurt that can decrease the risk of diabetes mellitus (DM) and its complications. The inhibition assays of the dipeptidyl peptidase IV (DPP- IV) and advanced glycation end products (AGEs) formation were conducted using 70% ethanol (EtOH) extraction of freeze-dried soymilk yogurt. Soymilk yogurt produced using Weissella confusa TOKAI 2 showed the highest inhibition rate in the α-amylase inhibition assay, while soymilk yogurt produced using Lactiplantibacillus plantarum TOKAI 17 showed the highest inhibition rates in the α-glucosidase and DPP-Ⅳ inhibition assays, respectively. Soymilk yogurt produced using Streptococcus macedonicus TOKAI 4 showed the highest inhibitory activities in Nω-(carboxymethyl) arginine (CMA) and Nε-(carboxymethyl) lysine (CML) formation, respectively. Furthermore, soymilk yogurt prepared using Lb. plantarum TOKAI 17 and Lactiplantibacillus pentosus TOKAI 35 exhibited higher proportions of aglycone isoflavones than soymilk and showed a higher fluorescent AGEs inhibitory activity than that of soymilk (p < 0.05). Interestingly, the inhibition assay assessing fluorescent AGEs formation using isoflavones indicated that aglycone-type isoflavones, such as genistein and daidzein, had higher inhibitory activities than that of glycosides (p < 0.05). These results indicate that soymilk yogurt produced using Lb. plantarum TOKAI 17 and Lb. pentosus TOKAI 35 had inhibitory effects on α-glucosidase, DPP-Ⅳ, and AGEs formation in vitro, and that aglycone isoflavones might inhibit the formation of fluorescent AGEs.

Therapeutic Potential of Myrrh, a Natural Resin, in Health Management through Modulation of Oxidative Stress, Inflammation, and Advanced Glycation End Products Formation Using In Vitro and In Silico Analysis

Oxidative stress, hyper-inflammatory responses, and protein glycation are the chief contributing factors in the pathogenesis of several diseases. This study aimed to explore the therapeutic role of myrrh in health management through in vitro and in silico studies. Antioxidant potential, anti-inflammatory potential, antiglycation, and advanced glycation end products (AGEs) formation inhibition activities were determined by various in vitro assays. Molecular docking was performed to predict the non-covalent binding of macromolecules (receptor) and a small molecule (ligand). Myrrh extract contained significant antioxidant activity as reflected by FRAP value (16.12 µg ascorbic acid/100 mg dry weight), the maximum percentage of DPPH scavenging (57.71%), and maximum hydrogen peroxide reducing activity (58.71%) at a concentration of 600 µg/mL. Further, the extract exhibited maximum protection from bovine serum albumin (BSA) denaturation inhibition (53.47%), anti-proteinase action (43.517%), and egg albumin denaturation inhibition (44.95%) at a dose of 600 µg/mL concentration. Myrrh is used in pharmacy as an antiseptic, anti-inflammatory, antimicrobial, antifungal, and anti-venom remedy. This study aimed to explore the antioxidant, anti-inflammatory, antiarthritic, antiglycation, and advanced glycation end products (AGEs) formation inhibition ability of methanolic myrrh extract. It was found that myrrh has good antioxidant potential due to plenty of flavonoids and polyphenolic compounds, as reflected by results of the 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) assay, FRAP (ferric reducing antioxidant power) test, and hydrogen peroxide reducing test. Furthermore, myrrh methanolic extract was found to be significantly effective against heat-induced albumin denaturation, and percent inhibition of denaturation increases with increased extract concentration. The presence of myrrh extract at a dose of 600 μg/mL decreased browning intensity (59.38%), percent aggregation index (59.88%), and percentage amyloid structure (56.13%). We used molecular docking tools to study the role of myrrh in oxidative stress (Catalase), antioxidant property (Superoxide dismutase), and antiviral property (spike protein S). The molecular docking analysis confirmed four phytoconstituents; 2,3-Furandione, Curzerene, delta-Elemene, and Furanoeudesma-1,3-Diene interact with catalase and superoxide dismutase. Curzerene and Furanoeudesma-1,3-Diene showed remarkable interaction with SARS-CoV-2 spike protein S. Our data suggest that myrrh resin extract can be used to develop a suitable alternative therapy for various diseases linked with oxidative stress, inflammation, glycation, and AGEs.

Determination of hemoglobin-derived advanced glycation end products deploying metal salts in solution: Towards development of low-cost detection technique

The elevated blood sugar in Type II diabetes results in protein glycation that leads to the formation of Advanced Glycation Endproducts (AGEs) and cause severe pathogenic complications such as cardiovascular diseases, nephropathies, retinopathies, neurodegenerative diseases, etc. In our earlier work we have shown that gold nanoparticles (AuNPs) can be synthesized both in presence and absence of external reducing agent by in vitro generated AGEs from Hemoglobin A0 (HbA0). In the current work we have found that these highly reactive Hb derived AGEs (Hb-AGEs) are also capable of reducing silver ions and synthesize silver nanoparticles (AgNPs) with a different plasmonic response than the control solutions. It was observed that the concentration of AGE and metal salts play a vital role in the formation of nanoparticles and time-dependent stabilization of the particles. The lowest detection limit (LOD) showed that the reactions are highly sensitive because as low as 1 ng/μl of AGEs can be detected. When reduction of the two metal ions (Au 3 + and Ag + ) were compared it was found that the AuNPs could be a better choice for the colorimetric sensing due to the appearance of plasmon in the visible range, while AgNPs could serve as a cost-effective determinant of AGEs. Therefore, in conclusion we confirm that AGEs can be detected just by deploying metal salts in solution.

Inhibition of advanced glycation end product formation and serum protein infiltration in bioprosthetic heart valve leaflets: Investigations of anti-glycation agents and anticalcification interactions with ethanol pretreatment

Bioprosthetic heart valves (BHV) fabricated from heterograft tissue, such as glutaraldehyde pretreated bovine pericardium (BP), are the most frequently used heart valve replacements. BHV durability is limited by structural valve degeneration (SVD), mechanistically associated with calcification, advanced glycation end products (AGE), and serum protein infiltration. We investigated the hypothesis that anti-AGE agents, Aminoguanidine, Pyridoxamine [PYR], and N-Acetylcysteine could mitigate AGE-serum protein SVD mechanisms in vitro and in vivo, and that these agents could mitigate calcification or demonstrate anti-calcification interactions with BP pretreatment with ethanol. In vitro, each of these agents significantly inhibited AGE-serum protein infiltration in BP. However, in 28-day rat subdermal BP implants only orally administered PYR demonstrated significant inhibition of AGE and serum protein uptake. Furthermore, BP PYR preincubation of BP mitigated AGE-serum protein SVD mechanisms in vitro, and demonstrated mitigation of both AGE-serum protein uptake and reduced calcification in vivo in 28-day rat subdermal BP explants. Inhibition of BP calcification as well as inhibition of AGE-serum protein infiltration was observed in 28-day rat subdermal BP explants pretreated with ethanol followed by PYR preincubation. In conclusion, AGE-serum protein and calcification SVD pathophysiology are significantly mitigated by both PYR oral therapy and PYR and ethanol pretreatment of BP.

6-Formyl Umbelliferone, a Furanocoumarin from Angelica decursiva L., Inhibits Key Diabetes-Related Enzymes and Advanced Glycation End-Product Formation.

Over the years, great attention has been paid to coumarin derivatives, a set of versatile molecules that exhibit a wide variety of biological activities and have few toxic side effects. In this study, we investigated the antidiabetic potential of 6-formyl umbelliferone (6-FU), a novel furanocoumarin isolated from Angelica decursiva. Numerous pharmacological activities of 6-FU have been previously reported; however, the mechanism of its antidiabetic activity is unknown. Therefore, we examined the action of 6-FU on a few candidate-signaling molecules that may underlie its antidiabetic activity, including its inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation (IC50 = 1.13 ± 0.12, 58.36 ± 1.02, 5.11 ± 0.21, and 2.15 ± 0.13 μM, respectively). A kinetic study showed that 6-FU exhibited mixed-type inhibition against α-glucosidase and HRAR and competitive inhibition of PTP1B. Docking simulations of 6-FU demonstrated negative binding energies and close proximity to residues in the binding pockets of those enzymes. We also investigated the molecular mechanisms underlying 6-FU’s antidiabetic effects. 6-FU significantly increased glucose uptake and decreased PTP1B expression in insulin-resistant C2C12 skeletal muscle cells. Moreover, 6-FU (0.8–100 μM) remarkably inhibited the formation of fluorescent AGEs in glucose-fructose-induced human serum albumin glycation over the course of 4 weeks. The findings clearly indicate that 6-FU will be useful in the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-related complications.

Antiglycation, antioxidant, antiacne, and photoprotective activities of crude extracts and triterpene saponin fraction of Sapindus saponaria L. fruits

Objective: To evaluate the photoprotective, antioxidant, antiglycation, and antiacne activities of crude extract (CESs) and triterpene saponin fraction (TSSs) of Sapindus saponaria. Methods: HPLC-MS purification was performed on a Symmetry TM C18 column. The saponins were identified by a UV detector. Antioxidant activity was evaluated by DPPH and O2 - radicals scavenging, and FRAP and TBARS assays. Glycation activity was assessed by relative electrophoretic mobility and inhibition of advanced glycation end products (AGEs) formation. Additionally, antiacne activity was determined by inhibition of Cutibacterium acnes, and photoprotective effect was evaluated by Mansur’s method. Results: Most of the triterpene saponins detected in the fraction by HPLC-MS analysis were hederagenin as the aglycon. CESs and TSSs presented varying antioxidant activity in DPPH (CESs: 75.69% and TSSs: 83.65%), FRAP (CESs: 425.39 μM TE/g DW and TSSs: 649.36 μM TE/g DW), TBARS (CESs: 42.96% and TSSs: 52.16%) and O2 - radicals scavenging (CESs: 61.33% and TSSs: 86.69%) tests. CESs and TSSs also exhibited antiglycation activity comparable to bovine serum albumin treated with aminoguanidine. In addition, CESs and TSSs showed inhibition of AGE formation (34.48% and 61.85%, respectively). Antiacne activity against Cutibacterium acnes was observed with a minimum inhibitory concentration equal to minimum bactericidal concentration (CESs: 36.11 μg/mL and TSSs: 18.34 μg/mL). In photoprotective assays, CESs and TSSs showed maximum absorbance of 1.42 to 0.20 and 2.80 to 1.30, respectively, in the wavelength range of 260 to 400 nm. Furthermore, CESs and TSSs showed sun protection factors of 8.89 and 14.89, respectively. Conclusions: Sapindus saponaria fruit extracts show strong antioxidant potential and antiglycation activity against bovine serum albumin glycation and AGE formation. Besides, they presented antibacterial activity against Cutibacterium acnes and photoprotective effect against UV-A and UV-B.

Bioactive phlorotannin as autophagy modulator in cervical cancer cells and advanced glycation end products inhibitor in glucotoxic C. elegans

Brown algae produce varieties of potent metabolites in order to adapt to extreme environment. Among these metabolites, polyphenols comprised of phlorotannins serve as powerful multifaceted bioactive with vast pharmacological potentials against non-communicable diseases like cancer and diabetes. In this study, a new phlorotannin was extracted from Padina tetrastromatica and characterized by Fourier Transform-Infrared, Nuclear Magnetic Resonance & Electronspray Ionization-Mass Spectroscopy. The phlorotannin exhibited potent DPPH and nitric oxide radical-scavenging activity in in-vitro, which were better than the standard antioxidants and other phlorotannins, previously reported. Further, the novel phlorotannin explicitly inhibited advanced glycation end-products formation in both in-vitro and in-vivo studies using hyperglycaemic C. elegans as an animal model and confirmed by live-cell fluorescence imaging. In addition, a significant modulation in expression of stress-responsive genes daf-2 and daf-16 were observed in phlorotannin treated hyperglycemic C. elegans. Moreover, the cytotoxic potential of phlorotannin (2,4,6-trioxa-1,3,5(1,3) tribenzenacyclohexaphane-15,35,55-triol) was explored for the first time in human cervical cancer cells (HeLa) and interesting observation was made that the cancer cell death was induced by activation of autophagy and pro-apoptotic protein markers i.e., LC3I/II, p21 and p53 that were confirmed by western-blot technique. Therefore, phlorotannin can be postulated as a potential bioactive for oxidative stress-mediated diseases, including diabetes and cancer.

The association between advanced glycation end products (AGEs) and ABC (hemoglobin A1C, blood pressure, and low-density lipoprotein cholesterol) control parameters among patients with type 2 diabetes mellitus

BackgroundDiabetes-induced chronic hyperglycemia results in the formation and aggregation of advanced glycation end-products (AGEs), which are products of non-enzymatic glycosylation of lipids or proteins. The development of diabetic complications can be accelerated by AGEs. In the current study, we aimed to explore the relationship between AGEs levels and ABC goals of diabetes control (A: Hemoglobin A1C < 7.0%, B: Blood pressure < 140/90 mmHg, and C: low-density lipoprotein cholesterol [LDL] < 100 mg/dL).MethodsIn the current cross-sectional study, 293 patients with type 2 diabetes mellitus (T2D), were enrolled. Demographic and clinical characteristics of the individuals were collected. AGEs levels were measured using quantitative fluorescence spectroscopy. Finally, the association of AGEs levels with patients' characteristics and ABC goals was assessed.ResultsHigher serum AGEs concentration was detected in older age, smoking patients and those with higher diastolic blood pressure, lower high-density lipoprotein (HDL) level, lower body mass index (BMI) and retinopathy. Moreover, the T2D patients who achieved higher numbers of ABC goals of diabetes were younger age (P-value = 0.003), with lower hemoglobin A1C (P-value = 0.001), fasting blood sugar (P-value = 0.002) diastolic blood pressure (P-value = 0.001), systolic blood pressure (P-value = 0.001), cholesterol (P-value = 0.001), LDL (P-value = 0.001), and AGEs (P-value = 0.023) levels. Diabetic patients with AGEs levels above 73.9% were about 2.2 times more likely to achieve none of ABC treatment goals (95% CI 1.107–3.616).ConclusionOur results revealed the relationship between AGEs and ABC goal achievement, and microvascular diabetic complications, and imply that AGEs measurement may be valuable in the monitoring of diabetic patients' complications and treatment adjustment.

α-Amylase inhibition, anti-glycation property and characterization of the binding interaction of citric acid with α-amylase using multiple spectroscopic, kinetics and molecular docking approaches

• Kinetics, fluorescence, UV–Vis, FT-IR, Mol. Docking affirmed α-amylase-CA interaction. • CA inhibited α-amylase activity by a mixed inhibition, K ic < K iu ; with moderate IC 50 . • AMY intrinsic fluorescence was quenched by CA via static mechanism. • CA binding altered AMY native conformation. • CA suppressed Advanced Glycation End-products (AGEs) formation. The quest to suppress complications associated with diabetes mellitus is ever increasing, while food additives and preservatives are currently being considered to play additional roles besides their uses in food enhancement and preservation. In the present study, the protective prowess of a common food preservative (citric acid, CA) against advanced glycation end-products (AGEs) formation and its binding interaction mechanism with α-amylase (AMY), an enzyme linked with hyperglycemia management, were examined. Enzyme inhibition kinetics, intrinsic fluorescence, synchronous and 3D fluorescence spectroscopies, ultraviolet–visible (UV–Vis) absorption spectroscopy, Fourier transform-infrared (FT-IR) spectroscopy, thermodynamics, and molecular docking analyses were employed. Results obtained showed that citric acid decreased α-amylase activity via mixed inhibition (IC 50 = 5.01 ± 0.87 mM, K ic = 2.42 mM, K iu = 160.34 mM) and suppressed AGEs formation (IC 50 = 0.795 ± 0.001 mM). The intrinsic fluorescence of free α-amylase was quenched via static mechanism with high bimolecular quenching constant (K q ) and binding constant (K a ) values. Analysis of thermodynamic properties revealed that AMY-CA complex was spontaneously formed (ΔG < 0), entropy driven (TΔS > ΔH), with involvement of electrostatic forces. UV–Vis, FT-IR and 3D fluorescence spectroscopies affirmed alterations in α-amylase native conformation due to CA binding interaction. CA interacted with His-101, Asp-197, His-299, and Glu-233 within AMY active site. Our findings indicated that CA could impair formation of AGEs and interact with α-amylase to slow down starch hydrolysis; vital properties in management of type 2 diabetes complications.

Effects of sodium bicarbonate and sodium phosphates on the formation of advanced glycation end-products in minced pork during cold storage

Effects of sodium bicarbonate and sodium phosphates on the formation of advanced glycation end-products in minced pork during cold storage

Debate: Could the litchi pericarp oligomeric procyanidins bioconverted by Lactobacillus plantarum increase the inhibitory capacity on advanced glycation end products?

Lactic acid bacteria (LAB) have already been used as fermentation strains to enhance the antioxidant capacity of polyphenols. Antioxidant capacity is one of the most important factors to inhibit advanced glycation end product (AGE) formation and could LAB increase the inhibitory capacity of procyanidins on AGEs formation? It was surprising that opposite results were obtained both in simulated food processing and gastrointestinal digestion systems. After incubation with Lactobacillus plantarum (L. plantarum), litchi pericarp oligomeric procyanidins (LPOPCs) were bioconverted to several phenolic acids, which increased the antioxidant activity as expected. However, antiglycation ability and trapping carbonyl compounds capacity both weakened and it might be the primary reason for decreasing the inhibitory effect on AGE formation. Furthermore, it was found that LPOPCs incubated with L. plantarum inhibited the activity of digestive enzymes and thus decreased the digestibility of glycated protein. Our study systematically proposed for the first time that procyanidins bioconversion is an effective means to improve the antioxidant activity but has no remarkable promoting effect on AGEs inhibition.

Neutrophil Activation by Mineral Microparticles Coated with Methylglyoxal-Glycated Albumin.

Hyperglycemia-induced protein glycation and formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of diabetic complications and pathological biomineralization. Receptors for AGEs (RAGEs) mediate the generation of reactive oxygen species (ROS) via activation of NADPH-oxidase. It is conceivable that binding of glycated proteins with biomineral particles composed mainly of calcium carbonate and/or phosphate enhances their neutrophil-activating capacity and hence their proinflammatory properties. Our research managed to confirm this hypothesis. Human serum albumin (HSA) was glycated with methylglyoxal (MG), and HSA-MG was adsorbed onto mineral microparticles composed of calcium carbonate nanocrystals (vaterite polymorph, CC) or hydroxyapatite nanowires (CP). As scopoletin fluorescence has shown, H2O2 generation by neutrophils stimulated with HSA-MG was inhibited with diphenyleneiodonium chloride, wortmannin, genistein and EDTA, indicating a key role for NADPH-oxidase, protein tyrosine kinase, phosphatidylinositol 3-kinase and divalent ions (presumably Ca2+) in HSA-MG-induced neutrophil respiratory burst. Superoxide anion generation assessed by lucigenin-enhanced chemiluminescence (Luc-CL) was significantly enhanced by free HSA-MG and by both CC-HSA-MG and CP-HSA-MG microparticles. Comparing the concentrations of CC-bound and free HSA-MG, one could see that adsorption enhanced the neutrophil-activating capacity of HSA-MG.

In vitro inhibition of advanced glycation end product formation by ethanol extract of milk thistle (Silybum marianum L.) seed

Glycation of proteins by reducing sugars produces toxic and immunogenic compounds called advanced glycation end products (AGEs). AGEs plays important role in the progression of typical diabetes complications. Silybum marianum L. contains powerful antioxidants that quench free radicals, which are unstable and reactive compounds that damage DNA and cellular structures. This study aimed to evaluate the antioxidant activities and the inhibitory effects of ethanol:water (1:1) extract of the Silybum marianum seed (SlyE) and silymarin (Sly) on fructose mediated protein glycation and AGE formation. The total amount of silymarin in SlyE was found to be 2.59 mg/gDW by HPLC. The composition of phenolic in the extract was found to be 262.70 µg gallic acid (GAE)/mg extract. The composition of flavonoids in the extract was found to be 10.50 µg quercetin (QUE)/mg extract. The seed exhibited ABTS radical cation decolourization inhibition with 70.4% at 300 mg concentration. Ferric reducing power of the extract was also evaluated. The SlyE and Sly also demonstrated strong inhibitory effects on the production AGEs in bovine serum albumin (BSA)/fructose model. SlyE and Sly has a significant effect in preventing oxidative protein damage, including the effect on the formation of fructosamines, α-dicarbonyls and protein carbonyl content (PCC). SlyE and Sly were able to prevent the glycoxidative damage of BSA. It can be concluded that the SlyE has antiglycating potential as well as antioxidant properties.

Fructosylation of human insulin causes AGEs formation, structural perturbations and morphological changes: an in silico and multispectroscopic study

Fructosylation of proteins results in the formation of advanced glycation end-products (AGEs). A diet rich in fructose along with hyperglycemia can cause fructose mediated glycation (fructosylation) of proteins, which results in AGEs formation. Insulin is a peptide hormone that is glycated when exposed to carbohydrates such as glucose. In this study, we have analysed the interaction of insulin with fructose and biophysically characterized fructose modified insulin. In silico studies performed through molecular docking and molecular dynamics simulation revealed that fructose binds to insulin with strong affinity resulting in the formation of insulin-fructose complex. Fructosylation of insulin caused hyperchromicity, loss of intrinsic fluorescence, gain in AGEs specific fluorescence and elevated the carbonyl and fructosamine content. Enhanced thioflavin T fluorescence suggested the presence of fibrillar structures at higher concentrations of fructose. Electron microscopy revealed the formation of characteristic amorphous and amyloid like aggregates at lower and higher concentrations of fructose, respectively. These findings show that fructosylation of insulin causes AGEs production, aggregation and alters its gross structural integrity. These changes may reduce the biological activity of insulin that can aggravate conditions like type II diabetes mellitus. Communicated by Ramaswamy H. Sarma

Glycation injury effects on aging and possible ways of prevention

Glycation is both a physiological and pathological process that mainly affects proteins, nucleic acids, and lipids. Advanced glycation end product (AGE) formation begins with the non-enzymatic glycation of free amino groups by sugars and aldehydes which leads to a succession of rearrangements of intermediate compounds and ultimately to irreversibly bound products known as AGEs. Recent studies have revealed the contributing roles of AGEs in the development of various aging-related conditions, such as diabetes, heart disease, and cancer. Controlling the blood sugar level is a natural method to inhibit glycation in diabetes. It is also seen from animal studies that exercise reduces the concentration of AGEs and highly reactive intermediates of AGE.

Heat-induced formation of advanced glycation end-products in ground pork as affected by the addition of acetic acid or citric acid and the storage duration prior to the heat treatments.

The heat-induced (121°C, 10 or 30min) formation of two potentially hazardous advanced glycation end-products (AGEs), protein-bound Nɛ -carboxymethyllysine (CML) and Nɛ -carboxyethyllysine (CEL), in pork as affected by citric or acetic acid (0.5, 1g/100 pork) and the storage duration (0°C, 0 - 8 d) prior to the heating was investigated. A longer storage time of raw pork resulted in higher levels of AGEs produced during the later heating, likely due to the accumulation of some AGE precursors during the storage. Depending on the acid level and heating time, adding acid in pork led to 30 - 54% (citric acid) or 14 - 48% (acetic acid) average reduction of heat-induced production of CML/CEL, which corresponded to the reduction of thiobarbituric acid reactive substances and Schiff bases. The marinating time of raw pork with an acid did not significantly affect (P=0.959 - 0.998) the acid's inhibition effect on heat-induced formation of CML/CEL.

Chemical constituents of Antidesma bunius aerial parts and the anti-AGEs activity of selected compounds

Thirty-three natural products were isolated from the aerial parts of Antidesma bunius, Euphorbiaceae, a plant used in Vietnamese traditional medicine against rheumatoid arthritis. All compounds were reported the first time for this species, and nine constituents resembled undescribed natural products, noticeably three coumarinolignans with 2,2-dimethyl-1,3-dioxolane moiety, two cyclopeptides, and two furofuran-type lignans connected with a phenylpropanoid moiety. The individual structures were elucidated by combining NMR and MS data, and their configuration was established by NOESY and ECD experiments and NMR calculations. Compounds with sufficient amount were analyzed for their inhibition of advanced glycation endproducts (AGEs) formation, metabolites involved in many diseases like Alzheimer, joint diseases or diabetes. With IC50 values below 0.2 mM rutin and p-hydroxyphenethyl trans-ferulate showed to be moderately active, both still being 10-times more active than the positive control aminoguanidine.

Formation of advanced glycation end-products in silver carp (Hypophthalmichthys molitrix) surimi products during heat treatment as affected by freezing-thawing cycles

Lipid oxidation and protein degradation, along with the formation of advanced glycation end-products (AGEs), including Nε-carboxymethyl-lysine (CML), Nε-carboxyethyl-lysine (CEL) and fluorescent AGEs, in raw and subsequently heated surimi products were investigated during freezing-thawing cycles. Lipid oxidation, protein degradation, Schiff base, and AGEs formation constantly increased during freezing-thawing cycles and heat treatment (P < 0.05). Heat-induced increase of AGEs in surimi products was accelerated by freezing-thawing treatment. Formation of CML in one-stage heated (45 °C, 30 min) samples increased from 0.10 ± 0.04 to 0.53 ± 0.11 mg/kg and CEL increased from 0.03 ± 0.32 to 0.92 ± 0.74 mg/kg. In two-stage heated samples (45 °C, 30 min and 90 °C, 20 min), CML increased from 0.86 ± 0.06 to 1.12 ± 0.11 mg/kg and CEL from 1.00 ± 0.34 to 2.11 ± 1.86 mg/kg, during up to 6 freezing-thawing cycles. Formation of fluorescent AGEs derived from heating was also significantly accelerated by freezing-thawing treatment (P < 0.01). Correlation analysis suggested that the chemical synthesis of AGEs in surimi products was promoted by lipid oxidation and protein degradation during freezing-thawing cycles. AGEs formation through Schiff base oxidation likely occurred only under thermal treatment since no relationship was found between Schiff base and AGEs levels in raw surimi products.