Influence of dietary advanced glycation end products on wound healing in nondiabetic mice

The present study was to determine advanced glycation end products (AGEs) in foods from different processes, and the influence of dietary AGEs on wound healing in nondiabetic mice. AGEs mixtures were extracted from local fast foods and foods prepared in lab. A BSA-AGEs mixture made by incubating glucose with bovine serum albumin (BSA) was used as a positive control. Burns were made on the skin of mice. The results showed that foods processed by high temperatures generated higher dietary AGEs. Nonwounded mice showed no observable adverse response to high dietary AGEs. However, high dietary AGEs caused severe inflammatory responses in wounded mice. The plasma level of high mobility group box 1 (HMGB1) and its mRNA in white blood cells were found to be significantly higher in the wounded mice fed with high dietary AGEs than others. We conclude that dietary AGEs worsen inflammation and delay wound healing in nondiabetic burned mice, which might be mediated by HMGB1.     

食源性晚期糖基化终末产物检测技术研究进展

晚期糖基化终末产物（advanced glycation end products,AGEs）是还原糖与蛋白质自由氨基间发生美拉德反应形成的一类异质性共价化合物的总称。研究发现食源性AGEs摄入后会在体内蓄积并对机体健康产生有害影响,因此有必要开展食物中各类AGEs的检测分析研究。食品中的AGEs种类繁多、结构复杂,目前缺少通用的检测分析方法。因此,本文针对食源性AGEs的结构和类型、与人体健康的关系以及相关检测技术进行综述,重点介绍食源性AGEs的免疫分析和仪器分析方法,深入探讨各类技术的特点和优劣势,并对后续研究方向进行展望,以期为食源性AGEs检测技术的发展以及相关研究体系的形成提供参考和借鉴。     

Advanced glycation end-products (AGEs) in foods and their detecting techniques and methods: A review

BackgroundAdvanced glycation end-products (AGEs) are a sort of complex products formed by the Maillard reaction between the carbonyls of reducing sugars and the free amino groups of amino acids. Some of AGEs ingested through foods accumulate in human body, causing a series of chronic diseases. However, due to the complex and varied structures, there is lack of systematic reviews on dietary AGEs.Scope and approachThis paper summarizes the aspects of AGE formation, influencing factors and hazards, as well as their distribution in foods. The detecting methods available for dietary AGEs are also highlighted. Finally, the main challenges and future efforts for studying AGEs in foods and their effects on health are discussed.Key findings and conclusionsThe study of AGEs has great significance in foods and human health. Although great advances in understanding the effects of AGEs in human body are made, more unequivocal guidance for dietary AGEs to people should be provided in future.     

Advanced Glycation End Products,Inflammation, and Chronic Metabolic Diseases: Links in a Chain?

Advanced glycation end products (AGEs) are a diverse group of compounds produced when reducing sugars react with proteins or other compounds to form glycosylated molecules. AGEs may form endogenously, and glycation of molecules may negatively affect their function. AGEs may also be consumed in food form with dietary AGEs reported to be particularly high in foods treated with high heat: baked, broiled, grilled, and fried foods. Whether dietary AGEs are absorbed in significant quantities and whether they are harmful if absorbed is a question under current debate. The American Diabetes Association makes no recommendation regarding avoidance of these foods, but many researchers are concerned that they may be pro-inflammatory and way worsen cardiac function, kidney function, diabetes and its complications and may even contribute to obesity.     

Arguing for the motion: yes, RAGE is a receptor for advanced glycation endproducts

Advanced glycation endproducts (AGEs) are an heterogenous class of compounds formed by diverse stimuli, including hyperglycemia, oxidative stress, inflammation, renal failure, and innate aging. Recent evidence suggests that dietary sources of AGE may contribute to pathology. AGEs impart diverse effects in cells; evidence strongly suggests that crosslinking of proteins by AGEs may irrevocably alter basement membrane integrity and function. In addition, the ability of AGEs to bind to cells and activate signal transduction, thereby affecting broad properties in the cellular milieu, indicates that AGEs are not innocent bystanders in the diseases of AGEing. Here, we present evidence that receptor for AGE (RAGE) is a receptor for AGEs.     

肠易激综合征饮食干预策略研究进展

肠易激综合征（Irritable Bowel Syndrome,IBS）是常见的胃肠道疾病之一,主要临床症状为腹痛、腹胀以及排便频率和性状异常。该病发病机制复杂,包括遗传因素、饮食差异、肠道菌群改变、胃肠道感染以及脑-肠轴异常等。目前缓解病症的主要方式是限制性饮食,如低“可发酵性寡糖、双糖、单糖和多元醇”（Fermentable Oligosaccharides,Disaccharides,Monosaccharides and Polyols,FODMAPs）饮食、低“晚期糖基化终产物”（Advanced Glycosylation End Products,AGEs）饮食、无麸质饮食以及低乳糖饮食等,能有效改善IBS患者的腹部不适症状。本文归纳了近几年国内外相关学者对于IBS的研究现状,包括IBS的病理生理学机制、低FODMAPs饮食和低AGEs饮食与IBS肠道菌群的关联、针对食物中FODMAPs成分和AGEs成分的定量检测手段以及食品加工处理技术降低食物中FODMAPs和AGEs含量的措施,以期为IBS患者提供健康有效的饮食干预策略。     

Accumulation and effects of dietary advanced glycation end products on the gastrointestinal tract in rats

The gastrointestinal (GI) tract represents the first barrier against the penetration of organisms by dietary advanced glycation end products (AGEs), but the tissue accumulation of AGEs and AGE‐induced effects on the GI tract have yet to be completely elucidated. This study aimed to investigate the tissue accumulation of AGEs and AGE‐induced oxidative stress and inflammation in the GI tract of rats after long‐term consumption of AGEs from bread crust (BC). The GI tract was then removed to analyse carboxymethyllysine (CML) and malondialdehyde (MDA) contents, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) and the levels of tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). This study demonstrates that the oral intake of AGEs promotes their accumulation in the GI tract, and AGEs attenuate the first‐line antioxidant defence and stimulate the inflammatory response of the GI tract by downregulating enzymatic antioxidative pathways and increasing inflammatory cytokine levels.     

色氨酸抑制体外模型中晚期糖基化终末产物形成机理

食源性晚期糖基化终末产物(advanced glycation end products,AGEs)与多种慢性疾病密切相关,尤其是糖尿病和肾脏疾病.为减少AGEs对机体的健康风险,降低食品中AGEs含量,本研究从13种氨基酸中筛选出具有良好AGEs抑制效果的色氨酸(tryptophan,Trp),利用牛血清白蛋白(bo...     

The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction

Advanced glycation end products (AGEs) are a heterogeneous group of molecules produced, non‐enzymatically, from the interaction between reducing sugars and the free amino groups of proteins, nucleic acids, and lipids. AGEs are formed as a normal consequence of metabolism but can also be absorbed from the diet. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes, and kidneys. Increased levels of AGEs are also detrimental to metabolic health and may contribute to the metabolic abnormalities induced by the Western diet, which is high in processed foods and represents a significant source of AGEs. While increased AGE levels are a consequence of diabetic hyperglycaemia, AGEs themselves activate signaling pathways, which compromise insulin signaling and pancreatic β‐cell function, thus, contributing to the development of type 2 diabetes mellitus (T2DM). Furthermore, AGEs may also contribute to the obesogenic effects of the Western diet by promoting hypothalamic inflammation and disrupting the central control of energy balance. Here, the role of dietary AGEs in metabolic dysfunction is reviewed with a focus on the mechanisms underpinning their detrimental role in insulin resistance, pancreatic β‐cell dysfunction, hypothalamic control of energy balance, and the pathogenesis of T2DM and obesity.     

槲皮素与葛根素对食品体系中非酶糖基化的抑制作用

通过对果糖胺、二羰基化合物、5-羟甲基糠醛（5-hydroxymethylfurfural,5-HMF）和荧光性末端产物的检测,考察槲皮素和葛根素对食品体系非酶糖基化反应的抑制作用。结果表明：槲皮素能促进非酶糖基化早期产物果糖胺和5-HMF的生成,对反应中期的二羰基化合物和非酶糖基化末端产物（advanced glycation end products,AGEs）具有较强的抑制作用;葛根素能促进果糖胺的生成,抑制二羰基化合物的生成,对5-HMF和AGEs无影响。这可能与槲皮素与葛根素的结构差异有关。     

竹叶黄酮与谷胱甘肽对食源性非酶糖基化的抑制

研究了竹叶黄酮与谷胱甘肽对食源性非酶糖基化反应的抑制作用。采用氯化硝基四氮唑蓝（NBT）还原实验检测糖基化反应产生的果糖胺,Girard-T实验检测二羰基化合物,295nm处的紫外吸收检测小分子醛类物质,荧光性非酶糖基化终产物AGEs的检测,以及用HPLC法检测5-羟甲基糠醛（5-HMF）含量。结果显示,竹叶黄酮可抑制果糖胺、二羰基化合物、有效抑制荧光性终产物;而谷胱甘肽可抑制二羰基化合物、小分子醛类及5-HMF。      

Genetic variability in the RAGE gene: possible implications for nutrigenetics, nutrigenomics, and understanding the susceptibility to diabetic complications

Complex chemical processes called nonenzymatic glycation and glycoxidation are one of the interesting examples of potentially harmful interaction between nutrition and disease. This review summarizes factors influencing the extent of glycoxidation in health and disease and especially focuses on the role of genetic variability in "glycoxidation-related genes" in a disease and diet-related pathogenesis. Possible interaction between genetic variability in relevant loci and dietary advanced glycation end products (AGEs) is considered. As AGEs possess a wide range of chemical and biological effects, the interindividual functional variability in systems dealing with glycoxidation could have a significant nutrigenomic and nutrigenetic consequences.     

High-pressure homogenization treatment of red seaweed Bangia fusco-purpurea affects the physicochemical,functional properties and enhances in vitro anti-glycation activity of its dietary fibers

In this study, high-pressure homogenization (HPH) technique was applied for the pretreatment of Bangia fusco-purpurea, and the effect of HPH on the composition, physiochemical and functional properties, and in vitro anti-glycation activity of dietary fiber from this seaweed (B. fusco-purpurea dietary fiber, BDF) was studied. Results showed that HPH significantly increased water-soluble dietary fiber (SDF) content in BDF. Water-holding capacity, oil-holding capacity, and glucose delay dialysis index of BDF were significantly enhanced after HPH treatment. Additionally, HPH significantly improved the in vitro anti-glycation activity of BDF by inhibiting the formation of advanced glycation end products (AGEs) and mitigating damage induced by AGEs on intestinal cells. These improvements could be attributed to the formation of the coarse and porous structure and greater exposure of hydroxyl groups of BDF caused by HPH treatment. These results implied the potential of HPH in seaweed processing and provided a scientific basis for the in-depth, comprehensive utilization of B. fusco-purpurea.Industrial relevanceHPH is an emerging non-thermal food processing technique with promising application potential in food industry. In this study, we found that HPH technique could significantly change the composition, improve physiochemical and functional properties and enhance anti-glycation activity of dietary fiber from seaweed B. fusco-purpurea. Our results validated the efficiency of HPH on dietary fiber modification, implying the potential of HPH in food industry and healthy industry.     

Toxicity of the AGEs generated from the Maillard reaction: on the relationship of food-AGEs and biological-AGEs

Advanced glycation end products (AGEs) are generated in the late stages of Maillard reaction in foods and biological systems. These products are mostly formed by the reactions of reducing sugar or degradation products of carbohydrates, lipids, and ascorbic acid. AGEs exist in high concentration in foods, but in relatively low concentrations in most of the biological systems. Recently, some AGEs have been reported to be toxic, and were proposed to be causative factors for various kinds of diseases, especially diabetes and kidney disorder, through the association with receptor of AGE (RAGE). It has also been reported that food-derived AGEs (food-AGEs) may not be a causative factor for pro-oxidation. However, the relationship of food-AGEs and biological-derived AGEs (biological-AGEs) is not clear. In this review, the following issues are discussed: the formation of AGEs in foods and biological systems; identification of the main AGEs in foods and biological systems; absorption of food-AGEs; the effects of AGEs in vivo; relationship between food-AGEs and biological-AGEs; possible defense mechanism against AGEs in vivo and finally, the problems to be solved concerning the toxicity of AGEs.     

食品中晚期糖基化末端产物的研究进展

晚期糖基化末端产物(advanced glycation end products, AGEs)是还原糖与氨基酸发生非酶褐变反应的产物之一。医学研究结果表明,AGEs与人类诸多疾病的发生有密切关系,而膳食摄入是体内AGEs的重要来源。但是由于AGEs种类较多,对于食品中的AGEs含量的检测尚缺乏标准的方法,食品加工工艺对食品中AGEs形成的影响报道较少。因此,本文从食品中AGEs形成、结构、检测方法及AGEs在体内代谢、对人体健康影响和预防措施等方面对AGEs进行了较系统的阐述,为进一步研究AGEs奠定基础。     

Radio fluorination and positron emission tomography (PET) as a new approach to study the in vivo distribution and elimination of the advanced glycation endproducts N epsilon-carboxymethyllysine (CML) and N epsilon-carboxyethyllysine (CEL).

After synthesis of fluorine-18 labelled analogues by [18F]fluorobenzoylation at the alpha-amino group, biodistribution and elimination of individual advanced glycation endproducts, namely N epsilon-carboxymethyllysine and N epsilon-carboxyethyllysine, were studied in comparison to lysine in rats after intravenous injection using positron emission tomography (PET). The [18F]radiofluorinated amino acids were fast distributed via the blood, followed by a rapid excretion through the kidneys. Elimination kinetics were similar for both AGEs and lysine. For CML and CEL, but not for lysine, a temporary liver accumulation could be observed, which was not connected with any metabolisation or enterohepatic circulation. No further accumulation in any tissues was observable, indicating that increased tissue levels of CML or CEL, which have been described for certain disorders, are exclusively derived from endogenous origin and should not depend on a dietary intake. However, under uremic conditions, an impaired kidney function might result in a significant increase of the AGE-load of blood and tissues. PET based on 18F-labelled AGEs proved to be a promising tool to elucidate the physiological fate of post-translationally modified amino acids and to clarify the role of AGEs as possible "glycotoxins".     

Curcumin against advanced glycation end products (AGEs) and AGEs-induced detrimental agents

Objectives: This study was aimed to review and collate effects of curcumin on generation of advanced glycation end products (AGEs) and AGEs induced detrimental agents.Methods: Pubmed, Googlescholar, ScienceDirect, and Scopus databases were searched. Searching was not limited to specific publication period. Only English language original articles (in vitro, experimental and human) which had examined the effect of curcumin on AGEs formation and AGEs induced apoptosis, oxidative stress or inflammatory responses were included. To review effect of curcumin on AGEs formation, search terms were as following: ‘‘curcumin” (title) and AGEs or pentosidine or methylglyoxal or carboxymethyllysine or glucosylation (title/abstract). Totally 104 articles were searched which 19 were selected for review. To review effect of curcumin on AGEs induced harmful agents, key words were as following: “curcumin” (title) and AGEs (title/abstract) and apoptosis or oxidative stress or DNA damage or cell injury or inflammatory or cell death or cell proliferation (title/abstract). Totally 126 articles were searched which 18 were found appropriate for review.Results: Regarding curcumin and AGEs formation, ten eligible articles (1 human trial, 5 animal models and 4 in vitro) and with regarding curcumin and AGEs-induced complications, 17 articles (5 on apoptosis, 9 on oxidative stress, and 3 on inflammatory responses) were selected. Except one, all studies indicated that curcumin is able to prevent AGEs formation and AGEs-induced disturbances with different potential mechanisms.Conclusion: Curcumin can inhibit AGEs formation and AGEs-induced disturbances. More RCT researches are suggested to evaluate beneficial effect of curcumin regarding AGEs in different age-related chronic diseases, with specific attention to AGEs memberships.     

Glycolaldehyde‐modified β‐lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE‐expressing human cell lines

Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and stimulate biological actions that are very similar as or identical to those induced by AGEs. Methods and results: In our study, we used glycolaldehyde‐modified β‐lactoglobulin preparations as model AGEs and employed two methods to remove endotoxin using either affinity columns or extraction with Triton X‐114 (TX‐114). Affinity column‐purified AGEs retained their ability to stimulate inflammatory signaling as measured by mRNA expression of inflammatory cytokines in the human lung epithelial cell line Beas2b. However, glycolaldehyde‐modified AGEs purified by extraction with TX‐114 did not show any stimulation of mRNA expression of inflammatory cytokines. The presence of a cell stimulating endotoxin‐like activity was demonstrated in the detergent phase after extraction with TX‐114, thus indicating that not AGEs but a lipophilic contamination was responsible for the stimulation of inflammatory signaling. Conclusion: Our results demonstrate that glycolaldehyde‐modified AGEs are unable to induce inflammatory signaling in receptor for AGE‐expressing cells. The observed cell‐activating activity can be ascribed to an endotoxin‐like lipophilic contamination present in AGE preparations and affinity column purification was insufficient to remove this contamination.     

Advanced glycation endproducts (AGEs) as uremic toxins.

Products of non-enzymatic glycation accumulate both in diabetic and non-diabetic patients with renal failure. The increase in concentration is presumably due to increased generation, secondary to oxidative stress and due to decreased (renal) elimination; whether accumulation of AGEs of dietary origin plays a role is currently under investigation. AGE's have been related to progression of diabetic (and possibly also non-diabetic) renal disease and to a number of complications of the uremic syndrome. These comprise beta-2-microglobulin-derived dialysis-related amyloidosis, dyslipidemia, vascular dysfunction and accelerated atherogenesis. A specific case is AGE related damage to the peritoneal membrane in CAPD patients. Removal of AGE by dialysis is negligible and even high flux dialysis eliminates only a quantitatively limited amount of AGE. In contrast, a rapid decrease of AGE concentrations in plasma is noted after renal transplantation. Dietary AGEs may contribute significantly to the total AGE load of the body, particularly in uremia.     

Advanced glycation endproducts (AGEs) as uremic toxins

Products of non‐enzymatic glycation accumulate both in diabetic and non‐diabetic patients with renal failure. The increase in concentration is presumably due to increased generation, secondary to oxydative stress and due to decreased (renal) elimination; whether accumulation of AGEs of dietary origin plays a role is currently under investigation. AGE's have been related to progression of diabetic (and possibly also non‐diabetic) renal disease and to a number of complications of the uremic syndrome. These comprise beta‐2‐microglobulin‐derived dialysis‐related amyloidosis, dyslipidemia, vascular dysfunction and accelerated atherogenesis. A specific case is AGE related damage to the peritoneal membrane in CAPD patients. Removal of AGE by dialysis is negligible and even high flux dialysis eliminates only a quantitatively limited amount of AGE. In contrast, a rapid decrease of AGE concentrations in plasma is noted after renal transplantation. Dietary AGEs may contribute significantly to the total AGE load of the body, particularly in uremia.