Phytochemicals as Potential Inhibitors of Advanced Glycation End Products: Health Aspects and Patent Survey

2021 ◽  
Vol 12 ◽  
Author(s):  
Annayara C. F. Fernandes ◽  
Jeane B. Melo ◽  
Vanize M. Genova ◽  
Ádina L. Santana ◽  
Gabriela Macedo
Keyword(s):  
Phenolic Compounds ◽  
Inflammatory Responses ◽  
Low Cost ◽  
Advanced Glycation Endproducts ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Synthetic Drugs ◽  
Peanut Skins

Background: Glycation is a chemical reaction that synthesize advanced glycation endproducts (AGEs). The AGEs irreversibly damage macromolecules present in tissues and organs, leading to the impairment of biological functions. For instance, the accumulation of AGEs induces oxidative stress and consequently inflammatory responses in human body, leading to the on set/worsening of diseases, including obesity, asthma, cognitive impairment, and cancer. There is a current demand on natural and low-cost sources of antiglycant agents. As a result, food phytochemicals presented promising results to inhibit glycation and consequently, the formation of AGEs. Objective: Here, we describe the mechanism of glycation on the worsening of diseases, the methods os detection, and the current findings on the use of phytochemicals (phenolic compounds, phytosterols, carotenoids, terpenes and vitamins) as natural therapeuticals to inhibit health damages via inhibition of AGEs in vitro and in vivo. Methods: This manuscript reviewed publications available in the PubMed and Science Direct databases dated from the last 20 years on the uses of phytochemicals to inhibit the AGEs in vitro and in vivo. Also, recent patents on the use of anti-glycant drugs were reviewed using the Google Advanced Patents database. Results and Discussion: Phenolic compounds have been mostly studied to inhibit AGEs. Food phytochemicals derived from agroindustry wastes, including peanut skins, and the bagasses derived from citrus and grapes are promising antiglycant agents via scavenging of free radicals, metal ions, the suppression of metabolic pathways that induces inflammation, the activation of pathways that promote antioxidant defense, the blocking of AGE connection with the receptor for advanced glycation endproducts (RAGE). Conclusion: Phytochemicals derived from agroindustry are promising anti-glycants, which can be included to replace synthetic drugs for AGE inhibition, and consequently to act as a therapeutical strategy to prevent and treat diseases caused by AGEs, including diabetes, ovarian cancer, osteoporosis, and Alzheimer’s disease.

scholarly journals A karbonilstressz szerepe a diabetes szövődményeinek kialakulásában

2019 ◽  
Vol 160 (40) ◽  
pp. 1567-1573 ◽  
Author(s):  
Kinga Makk-Merczel ◽  
András Szarka
Keyword(s):  
Diabetic Complications ◽  
Clinical Studies ◽  
Advanced Glycation Endproducts ◽  
Hydroxyl Group ◽  
Carbonyl Stress ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Oxidative Generation

Abstract: The relationship between the potentially developing complications of the 451 million people affected by diabetes and hyperglycaemia can be based on the enhanced generation of advanced glycation endproducts and the more intensive oxidative and carbonyl stress. Advanced glycation endproducts generated partly due to carbonyl stress play an important role in the pathogenesis of diabetic complications such as elevated arterial thickness, vascular permeability, enhanced angiogenesis or the more rigid vessels induced nephropathy, neuropathy, retinopathy. Furthermore, the elevated thrombocyte aggregation, the reduced fibrinolysis induced elevated coagulation, and the atherosclerosis or the mitochondrial dysfunction are important as well. The most potent target of both the non-oxidative and oxidative generation of advanced glycation endproducts can be the scavenging of α,β-unsaturated aldehydes. Although, aminoguanidine, the prototype of scavenger molecules, showed protection in different animal models, it failed in the human clinical studies. Finally, the clinical studies were terminated almost 20 years ago. The endogen dipeptide L-carnosine was also expected to mitigate the complications due to carbonyl stress. However, its clinical significance was limited by the serum carnosinases and by the consequent low serum stability and bioavailability. The carnosinase resistance of the molecule can be achieved by the change of the carboxyl group of the molecule to hydroxyl group. At the same time, the biosafety and the carbonyl stress scavenging activity of the molecule could be preserved. Although clinical studies could not be performed in the last six months, on the basis of the in vitro and in vivo results, carnosinole seems to be a promising compound to mitigate and prevent the diabetic complications. Thus it is worth to the attention of the clinicians. Orv Hetil. 2019; 160(40): 1567–1573.

scholarly journals Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

2017 ◽  
Author(s):  
Manuela Aragno ◽  
Raffaella Mastrocola
Keyword(s):  
Metabolic Diseases ◽  
Advanced Glycation Endproducts ◽  
Lipid Synthesis ◽  
Advanced Glycation ◽  
Antioxidant Defences ◽  
Glycation Endproducts ◽  
Cell Functions ◽  
Dietary Sugars

The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

scholarly journals Gastrointestinal digestion of dietary advanced glycation endproducts increases their pro-inflammatory potential

2021 ◽  
Author(s):  
T. van der Lugt ◽  
M. F. Vrolijk ◽  
T. F. H. Bovee ◽  
S. P. J. van Leeuwen ◽  
S. Vonsovic ◽  
...  
Keyword(s):  
Advanced Glycation Endproducts ◽  
Advanced Glycation ◽  
Gastrointestinal Digestion ◽  
Glycation Endproducts

Digestion of dietary advanced glycation endproducts (dAGEs) increases its pro-inflammatory potential in vitro.

scholarly journals Gastrointestinal digestion of dietary advanced glycation endproducts using an in vitro model of the gastrointestinal tract (TIM-1)

2020 ◽  
Vol 11 (7) ◽  
pp. 6297-6307 ◽  
Author(s):  
Timme van der Lugt ◽  
Koen Venema ◽  
Stefan van Leeuwen ◽  
Misha F. Vrolijk ◽  
Antoon Opperhuizen ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
In Vitro Model ◽  
Advanced Glycation Endproducts ◽  
Food Products ◽  
Advanced Glycation ◽  
Gastrointestinal Digestion ◽  
Glycation Endproducts ◽  
Vitro Model

In a sophisticated gastrointestinal model, dietary advanced glycation endproducts (dAGEs) in food products remain bound to proteins after digestion and concentrations increase.

scholarly journals Advanced glycation endproducts mediate pro-inflammatory actions in human gestational tissues via nuclear factor-κB and extracellular signal-regulated kinase 1/2

2007 ◽  
Vol 193 (2) ◽  
pp. 269-277 ◽  
Author(s):  
Martha Lappas ◽  
Michael Permezel ◽  
Gregory E Rice
Keyword(s):  
Oxidative Stress ◽  
Human Placenta ◽  
Advanced Glycation Endproducts ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Factor ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Gestational Tissues

Processes of human labour include increased oxidative stress, formation of inflammatory mediators (e.g. cytokines) and uterotonic phospholipid metabolites (e.g. prostaglandins). In non-gestational tissues, advanced glycation endproducts (AGE) induce the expression of pro-inflammatory molecules through mitogen-activated protein kinase and nuclear factor κB (NF-κB)-dependent pathways. Thus, the aim of this study was to investigate the effects of AGE on 8-isoprostane (a marker of oxidative stress), pro-inflammatory cytokine and prostaglandin release in human gestational tissues, and to define the signalling pathways involved. Human placenta and gestational membranes (amnion and choriodecidua combined; n=5) were incubated in the absence or presence of AGE–BSA (0.25, 0.5, 1 and 2 mg/ml) for 18 h. AGE significantly increased in vitro release of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, prostaglandin (PG)E2, PGF2α and 8-isoprostane from human placenta and gestational membranes. This was associated with a concomitant increase in NF-κB p65 activation and ERK 1/2 phosphorylation. AGE-stimulated 8-isoprostane, cytokine and prostaglandin production was significantly suppressed by the ERK 1/2 inhibitor U0126 and the NF-κB inhibitor BAY 11-7082. In conclusion, AGE mediates inflammatory actions in human gestational tissues. Protein kinases and the NF-κB pathway play an essential role in AGE signalling in human gestational tissues.

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