Inhibition Of Advanced Glycation End-products Formation Research Articles

Trapping mechanism by di-d-psicose anhydride with methylglyoxal for prevention of diabetic nephropathy

Di-d-psicose anhydride (DPA), derived from functional rare saccharide as d-psicose, is investigated for its strong chelating ability. Methylglyoxal (MGO), an important precursor of advanced glycation end-products (AGEs), promotes obesity, and causes complications such as diabetic nephropathy. On mesangial cells, DPA can substantially reduce the negative effects of MGO. DPA effectively trapping MGO in mesangial cells. The bonding properties of the DPA–MGO adduct were discussed by mass spectrometry and nuclear magnetic resonance (NMR). The NMR spectra of the DPA–MGO adduct provide evidence for chelation bonding. The inhibition of AGE formation and the mass spectrometry results of the DPA–MGO adduct indicate that DPA can scavenge MGO at a molar ratio of 1:1. DPA suppressed 330 % of the up-regulated receptor for an AGEs protein expression to a normal level and restored the suppressed glyoxalase 1 level to 86 % of the normal group. This research provides important evidence and theoretical basis for the development of AGE inhibitors derived from rare saccharide.

N-acetyl-L-hydroxyproline - A potent skin anti-ageing active preventing advanced glycation end-product formation invitro and exvivo.

Advanced glycation end-products (AGEs) represent a large group of compounds generated by a non-enzymatic reaction between reducing sugars and amino groups. The formation and accumulation of AGEs in the skin lead to protein crosslinking, dermal stiffening and yellowing, which ultimately contribute to cutaneous ageing. Amino acids have been described to exhibit anti-glycation effects. The objective of this study was to understand the inhibitory role of the amino acid derivative N-acetyl-L-hydroxyproline (NAHP) as an anti-glycation active for human skin. A cell-free assay investigating the inhibition of glycation of serum albumin by NAHP was used to determine the capability of NAHP to decrease AGE formation. Also, by assessing the amount of the AGE N-(carboxymethyl)lysine (CML) the anti-glycation abilities of NAHP were investigated utilizing dot blot analysis. The improvement of cell-matrix interaction by NAHP was determined invitro using a glycated fibroblast-populated collagen lattice (FPCL) dermis model. In skin biopsies, AGE autofluorescence was determined after treatment with NAHP and/or glucose exvivo. NAHP significantly and dose-dependently inhibited levels of AGEs, which were induced by the glycation of a protein solution. This decrease could be visualized by showing that the brownish appearance as well as the AGE-specific fluorescence of glucose-treated samples were reduced after the application of increasing amounts of NAHP. Also, CML formation was dose-dependently inhibited by NAHP. In FPCLs, the contractile capacity of fibroblasts was significantly disturbed after glycation. This could be prevented by the addition of NAHP. Compared to glyoxal-treated samples, the co-application of NAHP significantly decreased the diameter as well as the weight of glycated FPCLs. Exvivo application of glucose to skin explants showed a higher AGE fluorescence signal compared to control explants. Co-treatment with NAHP and glucose decreased the level of AGE fluorescence in comparison to glucose-treated explants. These data provide clear evidence that under glycation stress conditions treatment with NAHP inhibited AGE formation invitro and exvivo and prevented the loss of cellular contractile forces in a glycated dermis model. Thus, NAHP obviously provides a beneficial treatment option to counteract AGE-related changes in human skin such as dermal stiffening and yellowish skin appearance.

In vitro glycation of a tissue-engineered wound healing model to mimic diabetic ulcers.

Diabetic foot ulcers are a major complication of diabetes that occurs following minor trauma. Diabetes-induced hyperglycemia is a leading factor inducing ulcer formation and manifests notably through the accumulation of advanced glycation end-products (AGEs) such as N-carboxymethyl-lysin. AGEs have a negative impact on angiogenesis, innervation, and reepithelialization causing minor wounds to evolve into chronic ulcers which increases the risks of lower limb amputation. However, the impact of AGEs on wound healing is difficult to model (both in vitro on cells, and in vivo in animals) because it involves a long-term toxic effect. We have developed a tissue-engineered wound healing model made of human keratinocytes, fibroblasts, and endothelial cells cultured in a collagen sponge biomaterial. To mimic the deleterious effects induced by glycation on skin wound healing, the model was treated with 300 µM of glyoxal for 15 days to promote AGEs formation. Glyoxal treatment induced carboxymethyl-lysin accumulation and delayed wound closure in the skin mimicking diabetic ulcers. Moreover, this effect was reversed by the addition of aminoguanidine, an inhibitor of AGEs formation. This in vitro diabetic wound healing model could be a great tool for the screening of new molecules to improve the treatment of diabetic ulcers by preventing glycation.

Therapeutic Potential of Phlorotannin-Rich Ecklonia cava Extract on Methylglyoxal-Induced Diabetic Nephropathy in In Vitro Model.

Advanced glycation end-products (AGEs) play a vital role in the pathogenesis of diabetic complications. Methylglyoxal (MGO), one of the major precursors of AGEs, is a highly reactive dicarbonyl compound that plays an important role in the pathogenesis of diabetic nephropathy. This study was designed to evaluate the therapeutic potential of phlorotannin-rich Ecklonia cava extract (ECE) on MGO-induced diabetic nephropathy in in vitro models using mouse glomerular mesangial cells. ECE showed anti-glycation activity via breaking of AGEs-collagen cross-links and inhibition of AGEs formation and AGE-collagen cross-linking formation. The renoprotective effects were determined by assessing intracellular reactive oxygen species (ROS) and MGO accumulation, cell apoptosis, and the Nrf-2/ARE signaling pathway. MGO-induced renal damage, intracellular ROS production level, and MGO-protein adduct accumulation were significantly decreased by pretreating ECE. Moreover, ECE pretreatment exhibited preventive properties against MGO-induced dicarbonyl stress via activation of the Nrf2/ARE signaling pathway and reduction of RAGE protein expression in mouse glomerular mesangial cells. Collectively, these results indicated potential anti-glycation properties and prominent preventive effects of ECE against MGO-induced renal damage. Additionally, ECE may be utilized for the management of AGE-related diabetic nephropathy.

Effects of Methanolic Extract of Moringa oleifera on an In Vitro Model of Diabetic Nephropathy

Diabetic nephropathy (DN) is a severe diabetic complication and a leading cause of chronic kidney disease and renal failure worldwide. The high prevalence of end stage renal disease (ESRD) due to diabetes, coupled with the lack of efficient treatments, prompts the need for newer therapeutic strategies that overcome the drawbacks of the existing ones. In recent years, Moringa oleiferahas been identified as a plant with multiple nutritional and medicinal advantages. Importantly, previous studies have reported antioxidant and anti‐hyperglycemic properties of Moringa leaf extracts in diabetic rats. The growing interest in the potential use of nutraceuticals over conventional drugs along with the recent evidence of the beneficial effects of M. oleifera extract led us to investigate the effects of the methanol extract of M. oleifera on an in vitro model of human glomerular epithelial cells (HGEC).HGEC were chronically cultured in the presence of physiological (5mM) or high glucose (25mM) levels and treated with different concentrations of methanolic extract of M. oleifera(MOE). We evaluated the effect of MOE on the production of advanced glycation end‐products (AGE), cell viability, and response to oxidative stress. Our results indicate that MOE can effectively inhibit AGE formation in vitro and provide a cytoprotective effect to cells following an oxidative challenge. However, in line with prior data indicating that HGEC chronically exposed to high glucose are primed for apoptosis, these cells showed reduced viability following exposure to MOE compared to cells exposed to normal glucose. These results suggest that acute, high doses of MOE might not be beneficial following chronic exposure of kidney cells to glucose, but the possibility of a protective effect of MOE when administered early is worth exploring.

The Effect of Terpenoids ofDipsacus AsperoidesAgainst Alzheimer's Disease and Development of Simultaneous Analysis by High Performance Liquid Chromatography

Dipsaci Radix has been proved to represent an effective treatment strategy for Alzheimer's disease (AD), but the potential active components in Dipsaci Radix have not been evaluated by an AD-related bioassay. In this study, water fraction of Dipsaci Radix had been shown to have highest inhibitory effect on the AD-related activity tests, including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and advanced glycation end-product (AGE) formation. Therefore, a bioassay-guided approach yielded eleven terpenoid compounds (DR1-11) isolated from water fraction of Dipsaci Radix. Compounds (DR2,3,7 and 11) were stronger inhibitors of AChE. The BChE inhibitory effect of saponins was more positive than that of iridoids (DR1,4). Compounds (DR6,7,9-11) were good inhibitors of BACE1. Compounds (DR7-11) were more effective than positive control on the inhibition of AGE formation. Moreover, we firstly suggested concomitant new connections between the structure of Dipsaci Radix's isolated terpenoid compounds with AChE inhibitory activities and AGE formation. The study also represented that Dipsaci Radix was therapeutic for treating AD and dipsacus saponin XI (DR11) might be one of its active components. Our findings significantly provided the new foundation of the potential capacity bioactive components from Dipsaci Radix for AD remedy.

Ishige okamurae Ameliorates Methylglyoxal-Induced Nephrotoxicity via Reducing Oxidative Stress, RAGE Protein Expression, and Modulating MAPK, Nrf2/ARE Signaling Pathway in Mouse Glomerular Mesangial Cells.

Advanced glycation end-products (AGEs) such as methylglyoxal (MGO) play a vital role in the pathogenesis of nephropathy, a diabetic complication. In the present study, we evaluated the anti-glycation and renal protective properties of Ishige okamurae extract (IOE) against AGE-induced oxidative stress. HPLC analysis confirmed that bioactive phlorotannins such as diphlorethohydroxycarmalol and ishophloroglucin A are predominantly present in IOE. IOE showed strong anti-glycation activities via inhibition of AGE formation, inhibition of AGE–protein cross-linking, and breaking of AGE–protein cross-links. In addition, in vitro studies using mesangial cells demonstrated that IOE effectively suppressed intracellular reactive oxygen species production, intracellular MGO accumulation, and apoptotic cell death by MGO-induced oxidative stress, in addition to regulating the expression of proteins involved in the receptor for AGEs and nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathways. Therefore, IOE can serve as a natural therapeutic agent for the management of AGE-related nephropathy.

Ginsenoside derivatives inhibit advanced glycation end-product formation and glucose–fructose mediated protein glycation in vitro via a specific structure–activity relationship

Ginseng (Panax ginseng and red ginseng) extract has been reported to inhibit the formation of advanced glycation end-products (AGEs); however, the potential inhibitory activity of its major constituents (ginsenosides) against AGE formation is still unknown. In the present study, we investigated the inhibitory effect of ginsenoside derivatives on AGE formation. Herein, we assessed the activity of 22 ginsenosides, most of which significantly inhibited fluorescent AGE formation. Notably, ginsenoside Rh2, ginsenoside Rh1, and compound K exhibited the most potent AGE inhibitory potential with IC50 values of 3.38, 8.42, and 10.85 µM, respectively. The structure– activity relationship revealed that the presence of sugar moieties, hydroxyl groups, and their linkages, and the stereostructure of the ginsenoside skeleton played an important role in the inhibition of AGE formation. Furthermore, the inhibitory activity of the most active ginsenoside Rh2 on fructose-glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was explored. Rh2 (0.1–12.5 µM) inhibited the formation of fluorescent AGE and non-fluorescent AGE, as well as the level of fructosamine and prevented protein oxidation by decreasing protein carbonyl formation and protein thiol group modification. Rh2 also suppressed the formation of the β-cross amyloid structure of BSA. Ginsenosides might be promising new anti-glycation agents for the prevention of diabetic complications via inhibition of AGE formation and oxidation-dependent protein damage.

Diabetes and Pancreatic Cancer-A Dangerous Liaison Relying on Carbonyl Stress.

Simple SummaryDiabetic people have an increased risk of developing several types of cancers, particularly pancreatic cancer. The higher availability of glucose and/or lipids that characterizes diabetes and obesity is responsible for the increased production of highly reactive carbonyl compounds, a condition referred to as “carbonyl stress”. Also known as glycotoxins and lipotoxins, these compounds react quickly and damage various molecules in cells forming final products termed AGEs (advanced glycation end-products). AGEs were shown to markedly accelerate tumor development in an experimental model of pancreatic cancer and AGE inhibition prevented the tumor-promoting effect of diabetes. In humans, carbonyl stress has been associated with the risk of pancreatic cancer and recognized as a possible contributor to other cancers, including breast and colorectal cancer. These findings suggest that carbonyl stress is involved in cancer development and growth and may be the mechanistic link between diabetes and pancreatic cancer, thus representing a potential drug target.Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.

Diabetes promotes invasive pancreatic cancer by increasing systemic and tumour carbonyl stress in KrasG12D/+ mice

BackgroundType 1 and 2 diabetes confer an increased risk of pancreatic cancer (PaC) of similar magnitude, suggesting a common mechanism. The recent finding that PaC incidence increases linearly with increasing fasting glucose levels supports a central role for hyperglycaemia, which is known to cause carbonyl stress and advanced glycation end-product (AGE) accumulation through increased glycolytic activity and non-enzymatic reactions. This study investigated the impact of hyperglycaemia on invasive tumour development and the underlying mechanisms involved.MethodsPdx1-Cre;LSL-KrasG12D/+ mice were interbred with mitosis luciferase reporter mice, rendered diabetic with streptozotocin and treated or not with carnosinol (FL-926-16), a selective scavenger of reactive carbonyl species (RCS) and, as such, an inhibitor of AGE formation. Mice were monitored for tumour development by in vivo bioluminescence imaging. At the end of the study, pancreatic tissue was collected for histology/immunohistochemistry and molecular analyses. Mechanistic studies were performed in pancreatic ductal adenocarcinoma cell lines challenged with high glucose, glycolysis- and glycoxidation-derived RCS, their protein adducts AGEs and sera from diabetic patients.ResultsCumulative incidence of invasive PaC at 22 weeks of age was 75% in untreated diabetic vs 25% in FL-926-16-gtreated diabetic and 8.3% in non-diabetic mice. FL-926-16 treatment suppressed systemic and pancreatic carbonyl stress, extracellular signal-regulated kinases (ERK) 1/2 activation, and nuclear translocation of Yes-associated protein (YAP) in pancreas. In vitro, RCS scavenging and AGE elimination completely inhibited cell proliferation stimulated by high glucose, and YAP proved essential in mediating the effects of both glucose-derived RCS and their protein adducts AGEs. However, RCS and AGEs induced YAP activity through distinct pathways, causing reduction of Large Tumour Suppressor Kinase 1 and activation of the Epidermal Growth Factor Receptor/ERK signalling pathway, respectively.ConclusionsAn RCS scavenger and AGE inhibitor prevented the accelerating effect of diabetes on PainINs progression to invasive PaC, showing that hyperglycaemia promotes PaC mainly through increased carbonyl stress. In vitro experiments demonstrated that both circulating RCS/AGEs and tumour cell-derived carbonyl stress generated by excess glucose metabolism induce proliferation by YAP activation, hence providing a molecular mechanism underlying the link between diabetes and PaC (and cancer in general).

Potential of resveratrol in mitigating advanced glycation end-products formed in baked milk and baked yogurt

Baked milk and baked yogurt are two newly developed dairy products in the market. Throughout the processing, a long-time-high-temperature baking procedure was involved to enhance the formation of a brownish color and desirable flavors; meanwhile, advanced glycation end-products (AGEs) were extensively produced through Maillard reaction (MR). Resveratrol was first developed as a potential inhibitor of AGEs formation. The resveratrol at 1 μmol/L was achieved the highest inhibitory rate against the formation of dicarbonyl compounds in the baked milk (3-deoxyglucosone (3-DG): 68.77%, methylglyoxal (MG): 50.46%) and baked yogurt (3-DG: 35.50%, MG: 37.11%). Furthermore, the inhibitory effect of resveratrol on the formation of four AGEs was observed compared with those without adding resveratrol. The content of NƐ-(carboxymethyl)lysine (CML) and NƐ-(hydroxyethyl) lysine (CEL) as the two commonly detected AGEs were decreased by higher than 30% and 27% in the baked milk and baked yogurt, respectively, when the concentration of resveratrol was 0.1 μmol/L. Moreover, the generation of furosine was significantly inhibited by 1 μmol/L resveratrol, which was decreased to less than 40% and 60% in the baked milk and baked yogurt, respectively. The generation of pyrraline, in particular, was completely inhibited at a resveratrol concentration ranging from 0.1 to 10 μmol/L. Furthermore, the additional level of 0.1 μmol/L resveratrol achieved a high inhibitory effect of AGEs, and such an additional level would not alter the color and flavor profile of the baked milk and baked yogurt. Considering the high solubility of resveratrol in milk fat, it is speculated that resveratrol mainly acted at an early stage of the degradation, i.e., through the inhibition of the autocatalytic lipid oxidation that generates dicarbonyl compounds but played less as a dicarbonyl compounds scavenger. Significance of this study is developing resveratrol as the additive to inhibit the AGEs formation in the baked milk and baked yogurt without altering overall color and flavors, which let the dairy products become safer to consume.

Biosynthesized ZnO-NPs from Morus indica Attenuates Methylglyoxal-Induced Protein Glycation and RBC Damage: In-Vitro, In-Vivo and Molecular Docking Study

The development of advanced glycation end-products (AGEs) inhibitors is considered to have therapeutic potential in diabetic complications inhibiting the loss of the biomolecular function. In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized from aqueous leaf extract of Morus indica and were characterized by various techniques such as ultraviolet (UV)-Vis spectroscopy, Powder X-Ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). Further, the inhibition of AGEs formation after exposure to ZnO-NPs was investigated by in-vitro, in-vivo, and molecular docking studies. Biochemical and histopathological changes after exposure to ZnO-NPs were also studied in streptozotocin-induced diabetic rats. ZnO-NPs showed an absorption peak at 359 nm with a purity of 92.62% and ~6–12 nm in size, which is characteristic of nanoparticles. The images of SEM showed agglomeration of smaller ZnO-NPs and EDS authenticating that the synthesized nanoparticles were without impurities. The biosynthesized ZnO-NPs showed significant inhibition in the formation of AGEs. The particles were effective against methylglyoxal (MGO) mediated glycation of bovine serum albumin (BSA) by inhibiting the formation of AGEs, which was dose-dependent. Further, the presence of MGO resulted in complete damage of biconcave red blood corpuscles (RBCs) to an irregular shape, whereas the morphological changes were prevented when they were treated with ZnO-NPs leading to the prevention of complications caused due to glycation. The administration of ZnO-NPs (100 mg Kg−1) in streptozotocin(STZ)-induced diabetic rats reversed hyperglycemia and significantly improved hepatic enzymes level and renal functionality, also the histopathological studies revealed restoration of kidney and liver damage nearer to normal conditions. Molecular docking of BSA with ZnO-NPs confirms that masking of lysine and arginine residues is one of the possible mechanisms responsible for the potent antiglycation activity of ZnO-NPs. The findings strongly suggest scope for exploring the therapeutic potential of diabetes-related complications.

Use of Grape Pomace Phenolics to Counteract Endogenous and Exogenous Formation of Advanced Glycation End-Products.

The increase in consumption of “ultra-processed” foods has raised attention because of the possible adverse effects deriving from the Maillard reaction leading to the formation of toxic advanced glycation end-products (AGEs) during food processing. Additionally, the increasing trend and consumption of sugar-added foods and sweetened beverages is related to the endogenous formation of the same toxic compounds. However, ultra-processing in the context of food technology can bring challenges as well as a wealth of opportunities. Indeed, re-processing of grape pomace, a by-product of winemaking, can yield phenolic-rich fractions that efficiently counteract the effects of AGEs. In this review, the process of endogenous and exogenous AGE formation is illustrated. Then, the ability of grape phenolics to act as inhibitors of AGE formation is presented, including the efficacy ranking of various individual compounds measured in vitro and the outcome of in vivo double-blinded randomized crossover trials designed to prove the efficacy of grape phenolics as inhibitors of protein carbonylation. Finally, a survey of model functional foods added with grape phenolics, either to lower the dietary load of AGEs or to deliver antiglycation agents in vivo is listed in order to highlight the opportunity to develop safe and tailor-made “anti-AGEs” food applications.

Maize bran feruloylated oligosaccharides inhibited AGEs formation in glucose/amino acids and glucose/BSA models.

Various Maillard reaction systems were established to investigate the effect of maize bran feruloylated oligosaccharides (FOs) on the formation of both endogenous and exogenous advanced glycation end-products (AGEs) under different pH values. The formation of AGEs and four kinds of dicarbonyl compounds (glyoxal, methylglyoxal, 3-deoxyglucosulose, 2,3-butanedione) were determined by fluorescence spectrophotometry and HPLC, respectively. Results showed that maize bran FOs effectively inhibited the production of fluorescent AGEs. Moreover, increase in pH, temperature and concentration of FOs in reaction systems elevated the inhibition effects of feruloylated oligosaccharides, fluorescent AGEs and dicarbonyl compounds. Mainly because of the ester bond of FOs at high pH and/or temperature systems are readily to be hydrolyzed, resulting in the release of ferulic acid.

Identification of Pinocembrin as an Anti-Glycation Agent and α-Glucosidase Inhibitor from Fingerroot (Boesenbergia rotunda): The Tentative Structure⁻Activity Relationship towards MG-Trapping Activity.

Diabetes mellitus (DM) is a disease that is caused by a malfunction of carbohydrate metabolism, which plays an important role in the development of long-term diabetic complications. The excess glucose can be transformed to methylglyoxal (MG), a potential precursor of glycation. Glycation is a spontaneous non-enzymatic reaction that initially yields advanced glycation end-products (AGEs), which ultimately triggers several severe complications. Therefore, the inhibition of AGEs formation is the imperative approach for alleviating diabetic complications. The aim of this research was to investigate the glycation and α-glucosidase inhibitory abilities of compounds isolated from fingerroot. The dichloromethane extract afforded three flavanones, two chalcones, two dihydrochalcones, and one kavalactone. Most of the isolated compounds showed higher inhibition effect against AGEs formation than aminoguanidine (AG). Subsequent evaluation in MG-trapping assay indicated that their trapping potency was relatively comparable to AG. Their structure-activity relationships (SAR) of MG-trapping activity were investigated using the comparison of the structures of flavonoids. In addition, pinocembrin displayed moderate α-glucosidase inhibition against both maltase and sucrose, with IC50 values of 0.35 ± 0.021 and 0.39 ± 0.020 mM, respectively.

Cereal bran extracts inhibit the formation of advanced glycation endproducts in a bovine serum albumin/glucose model

AbstractBackground and objectivesThe adverse health effects of advanced glycation endproducts (AGEs) is of current interest; some previous research indicates that consuming these compounds may contribute to chronic diseases such as diabetes and heart disease. The objective of this study was to determine whether cereal bran extract from wheat (Jagger, JA), triticale (Spring Triticale, ST, and Thundercale, TH), and Rye (RY) can inhibit the formation of AGE in a bovine serum albumin/glucose (BSA/GLU) model.FindingsNε‐carboxymethyllysine (CML) levels showed ST extract inhibited AGE formation, but TH, RY, and JA extracts did not affect AGE formation in the BSA/GLU system. Subsequent HPLC analysis of ST extract revealed four major phenolic acids: vanillic (VA), chlorogenic (CHA), gentisic (GEA), and ferulic (FA). The results also showed antioxidant and antiglycation properties of these phenolic acids.ConclusionsGEA and CHA in ST extract were effective free radical scavengers and acted against dicarbonyl compounds.Significance and noveltyST bran extract may be considered as a natural source of inhibitors of in vitro formation of AGEs.

Screening and identification of inhibitors of advanced glycation endproduct formation from microalgal extracts.

The formation and accumulation of advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of many chronic diseases, such as aging, Alzheimer's disease, diabetes and diabetic complications. The present study was aimed to investigate the inhibitory effects of the extracts from nine microalgae on the formation of AGEs by using in vitro models and identify key antiglycation constituents of the microalgae. A BSA-glucose model with simulated physiological conditions was used to evaluate the inhibitory effect on total AGE formation. A BSA-MGO model was used to study the inhibitory activity against the dicarbonyl-induced AGE formation. The results showed that the aqueous acetone extracts exhibited stronger antiglycation activity than the other extracts (ethyl acetate and dichloromethane) and that the marine microalgal extracts were generally more effective than the freshwater ones. Their inhibitory rates ranged from >60% to 90% when used at a concentration of 0.5 mg mL-1. HPLC-DAD and UPLC-Q-TOF-MSE analyses revealed that fucoxanthin was likely the principal component which contributed to the observed antiglycation activity. Further analysis established a highly significant positive correlation (R2 > 0.95) between the fucoxanthin content and the antiglycation activity of the aqueous acetone extracts. This is the first report on the antiglycation activity of fucoxanthin. The findings of the present study have not only identified a promising inhibitor of AGE formation, but have also identified a valuable natural source of this phytochemical which possesses great potential to be developed as functional food ingredients and pharmaceutical products to help reduce health risks associated with AGEs.

Polyphenols from Euphorbia pekinensis Inhibit AGEs Formation In Vitro and Vessel Dilation in Larval Zebrafish In Vivo.

To identify active compounds in the roots of Euphorbia pekinensis for treatment of diabetic complications, an active column fraction from a 70% EtOH extract of E. pekinensis root was purified by preparative reversed-phase high-performance liquid chromatography, leading to the isolation of a new ellagic acid derivative, 3,3'-di-O-methylellagic acid 4-O-(6"-O-galloyl)-β-D-galactopyranoside (1: ), along with three known compounds, geraniin (2: ), 3,3'-di-O-methylellagic acid 4-O-β-D-xylopyranoside (3: ), and ellagic acid 3,3'-dimethyl ether (4: ). The structure of the new compound was established by extensive spectroscopic studies and chemical evidence. The inhibitory effects of isolated compounds 1: -4: on advanced glycation end-products (AGEs) formation were examined. All compounds exhibited considerable inhibition of AGEs formation and IC50 values of 0.41 - 12.33 µM, compared with those of the positive controls aminoguanidine (IC50 = 1122.34 µM) and quercetin (IC50 = 27.80 µM). In addition, the effects of 2: and 4: on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish were investigated; both compounds significantly reduced the HG-induced dilation of hyaloid-retinal vessels relative to the HG-treated control group.

Polyphenols from flowers of Magnolia coco and their anti-glycation effects.

We investigated the inhibitory effects of several plant extracts on advanced glycation end-products (AGEs) formation. Among tested samples, the flower extract of Magnolia coco showed significant inhibition of AGE formation. We isolated and characterized procyanidin oligomer and four other compounds from the flowers, and evaluated their inhibitory effects on AGE formation and the AGE-derived crosslink-cleaving activity of the isolated compounds.

The inhibition of advanced glycation end-products by five fractions and three main flavonoids from Camellia nitidissima Chi flowers

Camellia nitidissima Chi (CNC), belonging to Camellia genus (Theaceae family), is a medicinal and edible plant in China. Among the whole plant, the CNC flowers are especially precious, but the biological activities and the compositions of the CNC flowers are unknown. In this study, inhibiting effects on the formation of advanced glycation end-products (AGEs) of five CNC flowers fractions and three isolated compounds were investigated, these three compounds are two flavonoid glycosides and one flavanol, namely kaempferol 3-O-[2,3,4-Tri-O-acetyl-α-L-rhamnopyranosyl-(1→3)-2,4-di-O-acetyl-α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside, kaempferol 3-O-[2,3,4-Tri-O-acetyl-α-L-rhamnopyranosyl-(1→3)-4-O-acetyl-α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside and catechin. Among these five fractions, the ethyl acetate fraction showed the highest total phenolic contents and inhibiting effects on AGE formation. Bovine serum albumin (BSA)-glucose and BSA-methylglyoxal assay showed that the ethyl acetate fraction inhibited AGE formation by 74.49% and 34.3% at 1 mg/mL, respectively. As the main components, these three compounds also showed remarkable inhibiting effects on AGE formation by scavenging methylglyoxal, next two catechin-carbonyl adducts were identified using HPLC-ESI-MS/MS. The results showed that the CNC flowers had remarkable inhibiting effects on the formation of AGEs. The primary structure-activity relationship showed (1) the glycosides could reduce the inhibiting effects compared to kaempferol and (2) the acetyl at position 2‴ in compound 1 had no remarkable influence of the inhibiting effects on AGE formation compared to compound 2.