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The dysregulation of glucose metabolism that includes the modification of biomolecules with the help of glycation reaction results in the formation of advanced glycation end products (AGEs). The formation of AGEs may activate receptors for advanced glycation end products which induce intracellular signaling, ultimately enhancing oxidative stress, a well-known contributor to type 2 diabetes mellitus. In addition, AGEs are possible therapeutic targets for the treatment of type 2 diabetes mellitus and its complications. This review article highlights the antioxidant, anti-inflammatory, and antidiabetic properties of the Nymphaea species, and the screening of such aquatic plants for antiglycation activity may provide a safer alternative to the adverse effects related to glucotoxicity. Since oxidation and glycation are relatively similar to each other, therefore, there is a possibility that the Nymphaea species may also have antiglycating properties because of its powerful antioxidant properties. Herbal products and their derivatives are the preeminent resources showing prominent medicinal properties for most of the chronic diseases including type 2 diabetes mellitus. Among these, the Nymphaea species has also shown elevated activity in scavenging free radicals. This species has a load of phytochemical constituents which shows various therapeutic and nutritional value including anti-inflammatory and antioxidant profiles. To the best of our knowledge, this is the first article highlighting the possibility of an antiglycation value of the Nymphaea species by inhibiting AGEs in mediation of type 2 diabetes mellitus. We hope that in the next few years, the clinical and therapeutic potential may be explored and highlight a better perspective on the Nymphaea species in the inhibition of AGEs and its associated diseases such as type 2 diabetes mellitus., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Nayab Ishrat et al.)

The glycation reaction is the addition of free carbonyl group of reducing sugar to the free amino groups of proteins, lipoproteins and nucleic acids which results in the formation of an Amadori product which may ultimately lead to the generation of advanced glycation products (AGEs). The impact of AGEs on proteins consequently generates free radicals, "a key player" for the pathogenesis of diabetes mellitus. Gel electrophoresis was carried out to see the visual changes taking place as a result of the glycation reaction. In this study, the anti-glycation and anti-diabetic effect of wedelolactone (WED) was seen both in vitro and in vivo. WED reverted various biochemical markers in streptozotocin-induced diabetic rats along-with the improvements in the oxidative stress markers. It also decreased the levels of the glycated serum protein and fasting blood glucose. Broadly, WED not only inhibited glycation in vitro but also proved to be an effective in vivo anti-glycating agent. © 2018 IUBMB Life, 70(6):547-552, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

Glycation of biological macromolecule leads to the establishment of advanced glycation end products (AGEs) having implications in metabolic disorders. d‑ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the glycation reactions in vivo, however, no report have been published yet to discuss d‑ribose induced glycation of hemoglobin (Hb). Therefore, the present study was designed to investigate d‑ribose induced glycoxidative damage to Hb protein. Briefly, the commercially available Hb was glycated with d‑ribose for varying time intervals. The structural perturbation induced in glycated Hb (GHb) was confirmed by biophysical techniques viz., UV-visible, fluorescence spectroscopy, circular dichroism, Fourier transform infra-red spectroscopy, dynamic light scattering, MALDIthermal denaturation by UV-visible spectrophotometer and DSC. Biophysical techniques confirm the secondary and tertiary structural perturbation in GHb as compared to native Hb. The values of carbonyl content, hydroxy methyl furfural, thiobarbituric acid reactive substance and nitro blue tetrazolium were found to be increased and free lysine and free arginine content were decreased in the GHb due to structural change. Thus, results of this study have established that glycation with d‑ribose lead to the structural changes in the native Hb which might play an important role in pathophysiology metabolic diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Glycation is vital in terms of its damaging effect on macromolecules resulting in the formation of end products, which are highly reactive and cross‐linked irreversible structures, known as advanced glycation end products (AGEs). The continuous accumulation of AGEs is associated with severe diabetes and its associated ailments. Saccharides with their reducing ends can glycate amino acid side chains of proteins, among them glucose is well‐known for its potent glycating capability. However, other reducing sugars can be more reactive glycating agents than glucose. The D‐ribose is a pentose sugar‐containing an active aldehyde group in its open form and is responsible for affecting the biological processes of the cellular system. D‐ribose, a key component of many biological molecules, is more reactive than most reducing sugars. Protein glycation by reducing monosaccharides such as D‐ribose promotes the accelerated formation of AGEs that could lead to cellular impairments and dysfunctions. Also, under a physiological cellular state, the bioavailability rate of D‐ribose is much higher than that of glucose in diabetes, which makes this species much more active in protein glycation as compared with D‐glucose. Due to the abnormal level of D‐ribose in the biological system, the glycation of proteins with D‐ribose needs to be analyzed and addressed carefully. In the present study, human immunoglobulin G (IgG) was isolated and purified via affinity column chromatography. D‐ribose at 10 and 100 mM concentrations was used as glycating agent, for 1–12 days of incubation at 37°C. The postglycation changes in IgG molecule were characterized by UV‐visible and fluorescence spectroscopy, nitroblue tetrazolium assay, and various other physicochemical analyses for the confirmation of D‐ribose mediated IgG glycation. Significance statement: 1.D‐ribose‐induced glycation leads to structural perturbations in immunoglobulin G (IgG), the formation of IgG‐advanced glycation end products, and the generation of oxidative stress. 2.UV‐visible spectroscopy revealed the hyperchromicity of glycated IgG increases with the increase in the concentration of D‐ribose and time interval. 3.The early glycation products that is, Amadori products or ketoamines formed during D‐ribose mediated glycation of IgG were assessed by nitroblue tetrazolium assay and found to be increased initially in the first 5 days. 4.Hydroxymethylfurfural, carbonyl content, thiobarbituric acid reactive substances, and fluorescence intensity were found to be increased in glycated IgG as compared to the native analog. 5.Free lysine and arginine were found to be decreased in glycated IgG in comparison to the native conformer of the protein. [ABSTRACT FROM AUTHOR]

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and - N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs. [ABSTRACT FROM AUTHOR]

In recent years, there has been a progress in the study of glycation reaction which is one the possible reason for multiple metabolic disorders. Glycation is a nonenzymatic reaction between nucleic acids, lipids, and proteins resulting into the formation of early glycation products that may further lead to the accumulation of advanced glycation end products (AGEs). The precipitation of AGEs in various cells, tissues, and organs is one of the factors for the initiation and progression of various metabolic derangements including the cancer. The AGE interaction with its receptor "RAGE" activates the inflammatory pathway; yet, the downregulation of RAGE and its role in these pathways are not clear. We explore the effect of anticancer novel nanoassemblies on AGEs to determine its role in the regulation of the expression of RAGE, NFƙB, TNF-α, and IFN-γ. This paper is based on the in vivo and in vitro study in glycation and lung cancer model systems. Upon the treatment of nanoassemblies in both the model systems, we observed a protective effect of nanoassemblies over the inhibition of glycative and oxidative stress via mRNA expression analysis. The mRNA expression results corroborated with the reactive oxygen species (ROS), carboxy-methyl-lysine (CML), and fluorescence studies. In this study, we found that the presence of common factors for glycation and lung cancer is oxidative and glycative stress. This oxidation and glycation might be responsible for the initiation of inflammation which may further lead to uncontrolled growth of cells leading to cancer. This can be a strong association between lung cancer and glycation reaction. The intervention of the anticancer and antiglycation effects of multimodal nanoassemblies throughout the study promises a new pathway for cancer research. [ABSTRACT FROM AUTHOR]

Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively. [ABSTRACT FROM PUBLISHER]

Abstract: Aims: Glycation of proteins and DNA, results in the generation of free radicals causing structural modification of biomacromolecule. This leads to the generation of neo-antigenic epitopes having implication in diabetes mellitus. In this study, human placental DNA was glycated with fructose and its binding was probed with the serum antibodies from type 1 and 2 diabetes patients. Methods: Glycation was carried out by incubating DNA (10μg/ml) with fructose (25mM) for 5 days at 37°C. The induced structural changes in DNA were studied by spectroscopic techniques, thermal denaturation studies and agarose gel electrophoresis. Furthermore, binding characteristics of autoantibodies in diabetes (type 1 and 2) patients were assessed by direct binding and competitive ELISA. Results: DNA glycation with fructose resulted in single strand breaks, hyperchromicity in UV spectrum and increased fluorescence intensity. Thermal denaturation studies demonstrated the unstacking of bases and early onset of duplex unwinding. Type 1 diabetes patients exhibited enhanced binding with glycated DNA as compared to native form, while for type 2 diabetes only those with secondary complications (Nephropathy) showed higher binding. Conclusions: Glycation of DNA has resulted in structural perturbation causing generation of neo-antigenic epitopes that are better antigens for antibodies in diabetes patients. [Copyright &y& Elsevier]

The non-enzymatic glycosylation or non-enzymatic covalent modifications (NECMs) or glycation of cellular proteins result in the generation and accumulation of advanced glycation end products (AGEs) that are associated with the epigenetics of cancer. Epigenetic modifications are inheritable changes without alterations in the sequences of DNA. Glycation-mediated epigenetic mechanisms change the accessibility of transcriptional factors to DNA via rearrangement or modification in the chromatin structure and collaborate with gene regulation in the pathogenesis of cancer. Epigenetic mechanisms play a critical role in sustaining the tissue-specific gene expression. Distraction from normal epigenetic mechanism results in alteration of gene function, initiation and progression of cancer, and cellular malignant transformation. Epigenetic modifications on DNA and histones control enzymatic expressions of corresponding metabolic pathways, which in turn influence epigenetic regulation. Glycation of histones due to persistent hyperglycemia results in histone-histone and histone-DNA cross-linking in chromatin by compromising the electrostatic interactions, that affect the dynamic architecture of chromatin. Histone proteins are highly prone to glycation due to their basic nature and long half-lives, but the exact role of histone glycation in the epigenetics of cancer is still in the veil. However, recent studies have suggested the role of histone glycation mediated epigenetic modifications that affect cellular functioning by altering the gene expressions of related metabolic pathways. Moreover, dicarbonyls-induced NECMs of histones perturb the architecture of chromatin and transcription of genes via multiple mechanisms. Contrary to the genetic causes of cancer, a possible reversal of glycation-mediated epigenetic modifications might open a new realm for therapeutic interventions. In this review, we have portrayed a mechanistic link between histone glycation and cancer epigenetics. [ABSTRACT FROM AUTHOR]

Non-enzymatic glycation is the addition of a free carbonyl group of a reducing sugar to the free amino groups of proteins, which results in the formation of early and advanced glycation end-products (AGEs). Glycation reaction is profoundly associated with diabetes and its secondary complications, such as nephropathy and neuropathy. Glyoxal is a carbonyl species that reacts rapidly with the free amino groups of proteins to form AGEs. While the formation of AGEs with various glycating agents has previously been demonstrated, no extensive studies have been conducted to assess the role of quercetin in all three stages of glycation (early, intermediate and late). In this study, we report the glycation of HSA (human serum albumin) and its characterization by several spectroscopic techniques. Furthermore, inhibition of products at all stages of glycation was studied by various assays. Spectroscopic analysis suggests structural perturbations in the HSA macromolecule as a result of modification, which might be due to the generation of free radicals and the formation of AGEs. Inhibition in the formation of glycation has established that quercetin is a better and a more potent antiglycating agent than aminoguanidine at all stages of glycation. [ABSTRACT FROM AUTHOR]

Highlights: [•] This is the first ever report of the synthesis of GNps using glycation reaction. [•] These particles were proved effective against the bone cancer cell line (Saos-2). [•] These particles were found nontoxic on normal cell line (L-132). [Copyright &y& Elsevier]