Naturally occurring inhibitors against the formation of advanced glycation end-products

Advanced glycation end-products (AGEs) are the final products of the non-enzymatic reaction between reducing sugars and amino groups in proteins, lipids and nucleic acids. Recently, the accumulation of AGEs in vivo has been implicated as a major pathogenic process in diabetic complications, atherosclerosis, Alzheimer's disease and normal aging. The early recognition of AGEs can ascend to the late 1960s when a non-enzymatic glycation process was found in human body which is similar to the Maillard reaction. To some extent, AGEs can be regarded as products of the Maillard reaction. This review firstly introduces the Maillard reaction, the formation process of AGEs and harmful effects of AGEs to human health. As AGEs can cause undesirable diseases or disorders, it is necessary to investigate AGE inhibitors to offer a potential therapeutic approach for the prevention of diabetic or other pathogenic complications induced by AGEs. Typical effective AGE inhibitors with different inhibition mechanisms are also reviewed in this paper. Both synthetic compounds and natural products have been evaluated as inhibitors against the formation of AGEs. However, considering toxic or side effects of synthetic molecules present in clinical trials, natural products are more promising to be developed as potent AGE inhibitors.     

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。     

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。     

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.     

Evidence against dietary advanced glycation endproducts being a risk to human health

In vivo, advanced glycation endproducts (AGEs) are linked to various diseases, particularly those associated with diabetes. AGEs are also formed when many foods are thermally processed. The extent to which dietary AGEs are absorbed by the gastrointestinal (GI) tract and their possible role in the onset and promotion of disease are currently of considerable interest. This paper reviews information that supports the argument that dietary AGEs are not a risk to human health.     

Nε-(carboxymethyl)lysine formation from the Maillard reaction of casein and different reducing sugars

Food Science and Biotechnology - Dietary advanced glycation end products (AGEs) are involved in the pathogenesis of diabetic complications, atherosclerosis, and kidney disease. Formation of...     

Inhibition of advanced glycation endproduct formation by foodstuffs

The Maillard reaction, which is generally termed nonenzymatic browning or glycation, has been implicated in accelerated aging and diabetic complications in vivo. Although the molecular basis of glycation-induced pathogenesis is not well understood, the following have been noted: (1) protein glycation leads to the formation and accumulation of toxic advanced glycation endproducts (AGEs); (2) AGEs can permanently alter the structure and function of body proteins; and (3) the interaction between AGE-modified proteins and AGE-specific receptors (RAGEs) on the cell surface induces the overproduction of reactive oxygen species (ROSs) and inflammatory mediators, which leads to cellular disorders in biological systems. To date, studies that have examined the contribution of protein glycation to disease-states have primarily focused on the deleterious effects and related mechanisms of these glycotoxins. However, it remains unknown whether phytochemicals exert protective effects against glycotoxin-induced damage. Thus, the development and investigation of AGE inhibitors, especially the natural anti-AGE agents without adverse effects, may provide a therapeutic approach for delaying and preventing premature aging and diabetic complications. In this review, we provide an outline of anti-glycation properties of foodstuffs and/or their active components, and discuss their mechanisms of action.     

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.     

8种别样茶对AGEs抑制能力的筛选及其抑制机制探究

目的:本研究通过检测非酶糖基化终末产物（advanced glycation end-products,AGEs）生成量评价8种别样茶的糖基化抑制能力,并探究抑制效果较好的别样茶对AGEs生成各阶段的抑制作用机制。方法:本研究首先对8种别样茶水提液中总黄酮含量进行检测,接着通过构建体外蛋白质非酶糖基化模型实验检测了8种别样茶抑制AGEs生成的能力,最后择优测定其对糖基化早期产物果糖胺、中期产物活性羰基化合物以及蛋白质交联的抑制能力,从而探究其对非酶糖基化反应的抑制机制。结果:大叶苦丁茶（Ilex latifolia Thunb）和甜茶（Rubus suavissimus S. Lee）对AGEs的抑制效果在8种别样茶中较为突出,50 μg/mL时AGEs抑制率分别达到了76.31%±0.87%和81.75%±0.41%;大叶苦丁茶和甜茶主要通过抑制糖基化早期、中期产物的生成量来减少AGEs的产生。其中,500 μg/mL甜茶对果糖胺抑制率最高（59.12%）,蛋白质交联抑制率最高（81.41%）,5000 μg/mL大叶苦丁茶对活性羰基化合物抑制率最高（94.24%）。结论:大叶苦丁茶及甜茶可以作为抑制糖基化反应的功能食品,本研究可为具有抑制AGEs产生功效原料的综合开发利用提供一定的理论依据。     

Effect of the combination of low temperature vacuum heating with tea polyphenol on AGEs in sturgeon fillets

This study aimed to elucidate the information mechanism of advanced glycation end products (AGEs) in sturgeon fillets, and its inhibition by polyphenol. The results revealed that LTVH fillets (processed using low temperature vacuum heating method, LTVH) did not have lower values of AGEs than those treated using TC method (a typical thermal procedure using boiling water at 100 °C). The addition of tea polyphenol, on the other hand, drastically reduced the AGEs levels in LTVH fillets. An in vitro model including sturgeon myofibrillar protein and glucose was employed in this work to evaluate the inhibition of AGEs by tea polyphenol. The results showed that free Arginine was susceptible to interaction with glucose, which caused the development of AGEs. However, the addition of tea polyphenol competed with glucose for binding to free Arginine, leading to a substantial decrease in free Arginine concentration and an increase of free amino loss rate, resulting in the inhibition of AGEs generation. The LTVH technique, in combination with tea polyphenol, can be used to prevent the production of AGEs on fillets during the thermal treatment.     

食源性晚期糖基化终末产物对人体的健康危害研究进展

食源性晚期糖基化终末产物(Advanced Glycation End Products,AGEs)是指还原糖与蛋白质、核酸和脂质等大分子在非酶条件下发生美拉德反应作用生成的不可逆的共价化合物.研究表明,AGEs与人体的健康有密切联系,参与糖尿病及其并发症、阿尔兹海默症、肠道疾病等多种疾病的发生发展.本文将近年来AGE...     

Dietary advanced glycation endproducts (AGEs) and their health effects--PRO

Thermal processing of food results in the formation of various novel compounds, among others advanced glycation endproducts (AGEs). AGEs result from nonenzymatic glycation reactions between reducing sugars and free amino groups of proteins, peptides, or amino acids. Due to their potential noxious effects, alimentary AGEs are also called glycotoxins. This review provides a summary of the available evidence on the health effects of exaggerated intake of thermally treated food. Data from experimental studies in rodents and from clinical studies in healthy volunteers and in patients suffering from selected diseases in which AGEs are of pathogenetic importance (diabetes, chronic renal failure) are summarized. It is concluded that, an exaggerated intake of thermally processed foods may exert in vivo diabetogenic and nephrotoxic effects, induce low-grade inflammation, enhance oxidative stress, and promote atherosclerosis.     

亲水胶体对海绵蛋糕中晚期糖基化终末产物的抑制作用

为探究亲水胶体对晚期糖基化终末产物（advanced glycation end products,AGEs）生成的抑制作用,首先采用牛血清白蛋白（bovine albumin,BSA）-果糖、BSA-葡萄糖、BSA-丙酮醛（methylglyoxal,MGO）、BSA-乙二醛4 个化学模型,考察9 种经典亲水胶体在化学模型中的抗糖基化能力,筛选出抑制效果最佳的海藻酸（alginic acid,ALA）和黄原胶（xanthan gum,XG）作为研究对象,探究不同亲水胶体添加量（0.25%、0.5%、1.0%、1.5%、2.0%）及烘焙温度、时间对海绵蛋糕品质属性、AGEs形成和蛋白氧化产物的影响。明确最佳烘焙温度和时间为180 ℃、40 min,在此条件下分别添加0.5% ALA或2.0% XG能够显著降低海绵蛋糕中的荧光AGEs、非荧光AGEs和蛋白氧化产物含量。同时,ALA和XG的添加能够改善蛋糕的质构,提高蛋糕的水分含量。ALA和XG是一类很有前途的天然AGEs抑制剂,可以在烘焙之前添加至原料中,以减少烘焙食品中AGEs的生成。     

多酚对食源性晚期糖基化终末产物及其诱导的相关疾病的抑制作用研究进展

晚期糖基化终末产物通过引起活性氧产生、激活氧化应激反应从而诱发各种慢性代谢性疾病，如糖尿病性肾病、阿尔茨海默病、动脉粥样硬化和骨关节炎等。因此，晚期糖基化终末产物被认为是一种促进宿主细胞死亡和器官损伤的强毒性分子。多酚是自然界中常见的一种次生代谢产物，其结构多样，具有抗氧化、抗炎、抗菌等多种生物活性。天然产物多酚可通过捕获自由基、阻断炎症信号通路和与微生物相互作用等多种机制减少晚期糖基化终末产物的产生并抑制相关疾病的发生。本文综述了多酚对晚期糖基化产物及相关疾病的抑制作用，以期为多酚抑制晚期糖基化产物的进一步研究提供科学参考。     

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.     

Protective activity of flavonoid and flavonoid glycosides against glucose-mediated protein damage

The pathogenesis of diabetic vascular complications involves the formation of advanced glycation end-products (AGEs). AGEs accumulate slowly in the body with age and more rapidly in individuals with diabetes mellitus. An abnormally elevated blood glucose level in diabetes mellitus causes the formation of AGEs. Also, oxidative reactions contribute significantly to the formation of AGEs. The antioxidant flavonoids, quercetin, isoquercitrin, hyperin and cacticin from plants, decrease the formation of AGEs. This activity was examined using an in vitro glycation reaction. Of the tested compounds, isoquercitrin and hyperin showed a strong inhibitory activity against the formation of AGEs. These compounds showed inhibitory activities that were more potent than the positive control, aminoguanidine. These results suggest that isoquercitrin and hyperin may be promising agents to treat glycation-associated diseases.     

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.     

大豆7S蛋白-糖体系晚期糖基化终产物形成因素

目的:在大豆蛋白糖基化改性过程中会引发非酶糖基化反应,形成有害的晚期糖基化终产物(advanced glycation end products,AGEs),为提高食品安全性,模拟糖基化加工条件,构建大豆7S蛋白-糖体系模型,考察影响该体系AGEs形成的因素并进行有效调控。方法:采用荧光光谱法(λ_(ex)/λ_(em)=340 nm/465 nm)检测糖种类、还原糖质量浓度、pH值、反应温度、抑制剂种类及其浓度对AGEs形成的影响,采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳表征有害产物的形成及抑制效果。结果:糖种类为果糖、蛋白质与葡萄糖质量浓度配比1∶4、pH 9.2、反应温度121℃条件下产生荧光性AGEs的作用效果最强,4种黄酮类化合物槲皮素、染料木素、芦丁和木犀草素对荧光性AGEs的形成均可达到较好的抑制效果,且呈现良好的剂量-效应关系。结论:糖的种类与抑制剂种类对AGEs的形成有一定影响;降低还原糖质量浓度、降低pH值和降低反应温度,添加0.1 mmol/L大豆源染料木素可有效抑制大豆加工过程中有害产物AGEs的形成。     

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。     

芦丁抑制牛血清白蛋白糖基化

目的：考察芦丁对糖及活性二羰基化合物诱导的牛血清白蛋白（bovine serum albumin,BSA）糖基化的抑制效果。方法：建立牛血清白蛋白-丙酮醛（bovine serum albumin-methylglyoxal,BSA-MGO）、牛血清白蛋白-乙二醛（bovine serum albumin-glyoxal,BSA-GO）、牛血清白蛋白-还原糖反应体系,利用荧光光谱的方法考察MGO、GO和还原糖对于BSA糖基化的影响,并考察芦丁对于3 个反应体系中晚期糖基化终末产物（advancedglycation end products,AGEs）的抑制作用。结果：MGO、GO、还原糖浓度分别为0.5、0.5、10 mmol/L时引发BSA蛋白糖基化反应较为显著。对于上述3 个体系,芦丁的添加浓度分别为0.25、0.25、1 mmol/L时,能有效地抑制AGEs的形成。结论：芦丁能有效地抑制BSA-MGO、BSA-GO、BSA-还原糖体系的牛血清白蛋白糖基化。