scholarly journals Natural Products as a Source of Inspiration for Novel Inhibitors of Advanced Glycation Endproducts (AGEs) Formation

Planta Medica ◽  
2021 ◽  
Author(s):  
Stefaniya Velichkova ◽  
Kenn Foubert ◽  
Luc Pieters

AbstractProtein glycation, a post-translational modification found in biological systems, is often associated with a core defect in glucose metabolism. In particular, advanced glycation endproducts are complex heterogeneous sugar-derived protein modifications implicated in the progression of pathological conditions such as atherosclerosis, diabetic complications, skin diseases, rheumatism, hypertension, and neurodegenerative diseases. Undoubtedly, there is the need to expand the knowledge about antiglycation agents that can offer a therapeutic approach in preventing and treating health issues of high social and economic importance. Although various compounds have been under consideration, little data from clinical trials are available, and there is a lack of approved and registered antiglycation agents. Next to the search for novel synthetic advanced glycation endproduct inhibitors, more and more the efforts of scientists are focusing on researching antiglycation compounds from natural origin. The main purpose of this review is to provide a thorough overview of the state of scientific knowledge in the field of natural products from plant origin (e.g., extracts and pure compounds) as inhibitors of advanced glycation endproduct formation in the period between 1990 and 2019. Moreover, the objectives of the summary also include basic chemistry of AGEs formation and classification, pathophysiological significance of AGEs, mechanisms for inhibiting AGEs formation, and examples of several synthetic anti-AGEs drugs.

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 142 ◽  
Author(s):  
Vanesa Cepas ◽  
Massimo Collino ◽  
Juan C. Mayo ◽  
Rosa M. Sainz

Diets are currently characterized by elevated sugar intake, mainly due to the increased consumption of processed sweetened foods and drinks during the last 40 years. Diet is the main source of advanced glycation endproducts (AGEs). These are toxic compounds formed during the Maillard reaction, which takes place both in vivo, in tissues and fluids under physiological conditions, favored by sugar intake, and ex vivo during food preparation such as baking, cooking, frying or storage. Protein glycation occurs slowly and continuously through life, driving AGE accumulation in tissues during aging. For this reason, AGEs have been proposed as a risk factor in the pathogenesis of diet-related diseases such as diabetes, insulin resistance, cardiovascular diseases, kidney injury, and age-related and neurodegenerative diseases. AGEs are associated with an increase in oxidative stress since they mediate the production of reactive oxygen species (ROS), increasing the intracellular levels of hydrogen peroxide (H2O2), superoxide (O2−), and nitric oxide (NO). The interaction of AGEs with the receptor for AGEs (RAGE) enhances oxidative stress through ROS production by NADPH oxidases inside the mitochondria. This affects mitochondrial function and ultimately influences cell metabolism under various pathological conditions. This short review will summarize all evidence that relates AGEs and ROS production, their relationship with diet-related diseases, as well as the latest research about the use of natural compounds with antioxidant properties to prevent the harmful effects of AGEs on health.


2003 ◽  
Vol 375 (3) ◽  
pp. 581-592 ◽  
Author(s):  
Paul J. THORNALLEY ◽  
Sinan BATTAH ◽  
Naila AHMED ◽  
Nikolaos KARACHALIAS ◽  
Stamatina AGALOU ◽  
...  

Glycation of proteins forms fructosamines and advanced glycation endproducts. Glycation adducts may be risk markers and risk factors of disease development. We measured the concentrations of the early glycation adduct fructosyl-lysine and 12 advanced glycation endproducts by liquid chromatography with tandem mass spectrometric detection. Underivatized analytes were detected free in physiological fluids and in enzymic hydrolysates of cellular and extracellular proteins. Hydroimidazolones were the most important glycation biomarkers quantitatively; monolysyl adducts (Nε-carboxymethyl-lysine and Nε-1-carboxyethyl-lysine) were found in moderate amounts, and bis(lysyl)imidazolium cross-links and pentosidine in lowest amounts. Quantitative screening showed high levels of advanced glycation endproducts in cellular protein and moderate levels in protein of blood plasma. Glycation adduct accumulation in tissues depended on the particular adduct and tissue type. Low levels of free advanced glycation endproducts were found in blood plasma and levels were 10–100-fold higher in urine. Advanced glycation endproduct residues were increased in blood plasma and at sites of vascular complications development in experimental diabetes; renal glomeruli, retina and peripheral nerve. In clinical uraemia, the concentrations of plasma protein advanced glycation endproduct residues increased 1–7-fold and free adduct concentrations increased up to 50-fold. Comprehensive screening of glycation adducts revealed the relative and quantitative importance of α-oxoaldehyde-derived advanced glycation endproducts in physiological modification of proteins–particularly hydroimidazolones, the efficient renal clearance of free adducts, and the marked increases of glycation adducts in diabetes and uraemia–particularly free advanced glycation endproducts in uraemia. Increased levels of these advanced glycation endproducts were associated with vascular complications in diabetes and uraemia.


2008 ◽  
Vol 115 (11) ◽  
pp. 1545-1556 ◽  
Author(s):  
Katrin Bigl ◽  
Frank Gaunitz ◽  
Annett Schmitt ◽  
Sven Rothemund ◽  
Reinhard Schliebs ◽  
...  

2011 ◽  
Vol 30 (6) ◽  
pp. 317-324 ◽  
Author(s):  
Nadeem A. Ansari ◽  
Moinuddin ◽  
Rashid Ali

Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs). This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related diseases. Antigenic characteristics of glycated lysine residues in proteins together with the presence of serum autoantibodies to the glycated lysine products and lysine-rich proteins in diabetes and arthritis patients indicates that these modified lysine residues may be a novel biomarker for protein glycation in aging and age-related diseases.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 564
Author(s):  
Haruki Watanabe ◽  
Myoungsun Son

The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.


Heliyon ◽  
2020 ◽  
Vol 6 (11) ◽  
pp. e05364
Author(s):  
Isabella M. Atzeni ◽  
Jeltje Boersema ◽  
Hendri H. Pas ◽  
Gilles F.H. Diercks ◽  
Jean L.J.M. Scheijen ◽  
...  

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