Dietary AGEs and ALEs and risk to human health by their interaction with the receptor for advanced glycation endproducts (RAGE)--an introduction

The receptor for advanced glycation endproducts (RAGE) has a well-substantiated role in cell dysfunction and mechanisms of inflammatory disease. The physiological agonists of RAGE are less certain: S100/calgranulin proteins, high mobility group-1 protein HMGB1 and other proteins are candidate agonists. It increasingly appears unlikely proteins modified by advanced glycation endproducts are effective agonists in vivo. In the following debate, Professors Ann Marie Schmidt and Claus Heizmann gave arguments and evidences for and against the motion. Recent evidence suggesting the activation of RAGE impairs the enzymatic defence against glycation provided by glyoxalase 1 (Glo 1) suggests that studies of RAGE will continue to be of importance to our understanding of the physiological significance of protein glycation.     

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.     

Inhibitory effects of microalgal extracts on the formation of advanced glycation endproducts (AGEs)

The antiglycative activities of 20 microalgae at different growth phases were evaluated for the first time. In a bovine serum albumin (BSA)-glucose system, ethyl acetate fractions of green microalgae Chlorella and diatom Nitzschia laevis exhibited the highest inhibitory effects against the formation of total advanced glycation endproducts (AGEs) (inhibition rates: 81.76–88.02% and 91.68%) at the concentration of 500 ppm. Such abilities were higher than the effect of 1 mM aminoguanidine (AG) solution (inhibition rate: 80.51%), a commonly used inhibitor of glycation process. In addition to total AGEs, these fractions were also found to be effective in the blockage of the formation of two specific AGEs, pentosidine and N^ε-Carboxymethyllysine (CML). Different from many other plant species, AGE inhibitory abilities of selected microalgae were not due to the presence of phenolic compounds. HPLC and gas chromatography (GC) analysis revealed that carotenoids in Chlorella and unsaturated fatty acids, mainly of linoleic acid, arachidonic acid and eicosapentaenoic acid in Nitzschia laevis contributed to their strong antiglycative capacities.     

Inhibitory effect of mung bean extract and its constituents vitexin and isovitexin on the formation of advanced glycation endproducts

The anti-glycation activity of four kinds of beans including mung bean, black bean, soybean and cowpea were evaluated. Aqueous alcohol extract of mung bean exhibited the strongest inhibitory activity against the formation of fluorescent advanced glycation endproducts (AGEs) in a bovine serum albumin (BSA)-glucose model, and the inhibitory activities of extracts of the four beans were found to be highly correlated with their total phenolic contents (R² = 0.95). Subsequent HPLC analysis of mung bean extract revealed two major phenolics which were purified and identified as vitexin and isovitexin by spectral methods. In the anti-glycation assays, both vitexin and isovitexin showed significant inhibitory activities against the formation of AGEs induced by glucose or methylglyoxal with efficacies of over 85% at 100 μM. In another assay, vitexin and isovitexin failed to directly trap reactive carbonyl species, such as methylglyoxal, suggesting that their anti-glycation activities may mainly be due to their free radical scavenging capacity.     

The mechanism by which dietary AGEs are a risk to human health is via their interaction with RAGE: arguing against the motion

We are interested in the regulation of intracellular calcium and the various diseases associated with an altered regulation of this second messenger. More recently, we also became interested in pathologies involving the Ca2+-binding S100 proteins and AGEs and their association with the multifunctional Receptor for Advanced Glycation Endproducts (RAGE).     

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".     

Inhibitory effects of Lemon balm (Melissa officinalis, L.) extract on the formation of advanced glycation end products

Lemon balm (Melissa officinalis) is a medicinal herb possessing functional compounds with unexplored anti-glycative action. The anti-glycative activity of Lemon balm extract was evaluated in the bovine serum albumin (BSA)/glucose system. The level of glycation, conformational alterations and protein binding to RAGE receptors were assessed by specific fluorescence, Congo red binding assay, circular dichroism, ligand and Western blotting. Ethanol fractions of Melissa leaf exhibited the highest inhibitory effects on the formation of advanced glycation end products (AGEs) and the late stage of glycation process. Significant alteration in the secondary structure of albumin was observed upon glycation, which was mitigated by applying the herb extract. Moreover, upon treatment with balm extract, glycated albumin adopts a secondary structure impeding its detection by RAGE receptors of microglial cells. Our results represent the anti-glycative properties of Melissa extract and its application for possible treatment of AGE-associated diseases.     

Formyline, a new glycation compound from the reaction of lysine and 3-deoxypentosone

A previously uncharacterized glycation compound was isolated from a reaction mixture of N-α-Boc-lysine and 3-deoxypentosone by semi-preparative ion-exchange chromatography and was identified by nuclear magnetic resonance (NMR) spectroscopy as 6-(2-formyl-1-pyrrolyl)-l-norleucine (formyline). 3-Deoxypentosone and pentoses like ribose, arabinose, or xylose were identified as the predominant precursors of the new glycation compound, but formyline can also be formed from lysine and degradation products of disaccharides and glucuronic acid. The Amadori products lactuloselysine and ribuloselysine, which were synthesized by improved methods and characterized by NMR spectroscopy, were shown not to form formyline when heated in dry state without lysine added, indicating that reactions between the lysine side chain and dicarbonyl compounds are the main pathways for formyline formation rather than transformation of lysine containing Amadori products. Finally, it was shown by HPLC analysis after enzymatic digestion that peptide-bound formyline can be formed during incubation of casein and 3-deoxypentosone under conditions comparable to food processing.     

Rapid and advanced tools for mycotoxin analysis: a review

The problems associated with mycotoxin contamination of foods and feeds are well established and, in many cases, have been known for a long time. Consequently, the techniques for detecting known mycotoxins are quite advanced and range from methods for directly detecting the toxins themselves, based upon physical characteristics of the toxins, to methods for indirectly detecting the toxins, such as immunoassays. This review focuses on recent technologies that can be used to detect mycotoxins and, as such, is not a comprehensive review of the mycotoxin analytical literature. Rather, the intent is to survey the range of technologies from those that are instrument intensive such as modern chromatographic methods to those that require no instrumentation, such as certain immunoassays and biosensors. In particular, mass spectrometric techniques using ambient ionization offer the intriguing possibility of non-destructive sampling and detection. The potential application of one such technique, desorption electrospray ionization (DESI), is demonstrated for fumonisin B₁ on maize. While methods for detecting mycotoxins are quite advanced, the need remains for assays with increased throughput, for the exploration of novel detection technologies, and for the comprehensive validation of such technologies as they continue to be developed.     

东港股份：市场唯先 用户至上

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