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Biosynthetic procedure is one of the best alternatives, inexpensive and ecologically sound for the synthesis of titanium dioxide (TiO2) nanoparticles using a methanolic extract of medicinal plant. The main prospect of this study was to investigate the antiglycation activity of the TiO2 nanoparticles (TNP) prepared by ethanolic leaf extract of the Coleus scutellarioides. In this study, biosynthesized TNP characterized with UV‐Visible spectroscopy, X‐ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscope. These TNP were further investigated with respect to their antiglycation property and it was checked in the mixture of d‐ribose glycated bovine serum albumin (BSA) by measuring ketoamine, carbonyl content, Advanced glycation end products (AGEs) and aggregation of protein instigated by glycation process. The inhibitory effect of TNP to restore the structure of BSA in presence of d‐ribose were also characterize by biophysical techniques mentioned above. Therefore, the findings of this study suggest repurposing of TNP for its antiglycation property that could be helpful in prevention of glycation instigated AGEs formation and structural loss of proteins. Significance statement: Provide a low cost green synthesis method for the synthesis of biologically active titanium dioxide (TiO2) nanoparticles.Provide the structural characterization of green synthesized TiO2 nanoparticles (TNP).An insight to identify the TNP as significant glycation inhibitor.Study suggest antiglycation potential detection of plant based TNP as possible therapeutic invention for hyperglycemia assisted diabetes and associated diseases. [ABSTRACT FROM AUTHOR]

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]

Glycation of biological macromolecules, due to hyperglycemia, promotes the formation of advanced glycation end products (AGEs). It is accelerated in diabetic patients and is responsible for the pathophysiology and progression of diabetes. Previous reports have shown that amount of AGEs formation and glycation-induced structural damage is higher in hemoglobin (Hb) than other proteins present in blood. In our previous study, we have shown structural changes in Hb by D-ribose which may result into the generation of immunogenic neo-epitopes. Thus, we hypothesized that D-ribose induced structural perturbations in Hb, could result in the formation of neo-epitopes which may provoke an auto-immune response and may also be involved in the immuno-pathogenesis of diabetes type-2 associated complications. Therefore, in the current study, we analyzed the prevalence of autoantibodies in diabetic patient's sera against D-ribose glycated-Hb by direct binding and competitive ELISA. Direct binding ELISA confirmed that autoantibodies in diabetic patients exhibit significantly high binding with D-ribose glycated-Hb as compared to its native form. The antigen binding specificity of these antibodies was also screened by competitive inhibition ELISA. We also used D-glucose glycated-Hb as a positive control to detect the presence of auto-antibodies by direct binding and inhibiton ELISA. We found that D-glucose glycated-Hb binds with T2DM samples but the affinity to binding is lower than D-ribose glycated-Hb. The overall findings of this study suggest the prevalence of circulating autoantibodies against D-ribose glycated-Hb in diabetic patients and thus, the level of these autoantibodies may be used as biomarker for progression of diabetes. [ABSTRACT FROM AUTHOR]

There are accumulating evidences suggesting that interaction between advanced glycation end products (AGEs) and their receptors (RAGEs) induces oxidative stress and subsequently encourages inflammatory reactions, thereby resulting in progressive alteration in renal architecture and function. Interventions that reduce the tissue burden of AGEs have yielded significant positive results in inhibiting the progression of diabetic complications such as diabetic nephropathy. Lycopene, a carotenoid, plays an important role in protection against oxidative stress and hence might prove an efficient antiglycating agent. Current study investigates the effect of lycopene in downregulating the menace caused by ribose-induced glycation both in vitro and in vivo. We observed that treatment with lycopene decelerated the ribose induced AGE formation in HK-2 cells and in rat kidneys thereby downregulating the expression RAGE. HK-2 cells with decreased levels of RAGE showed a decline in nuclear factor κB (NFκB) and matrix metalloproteinase 2 (MMP 2) expressions. Administration of ribose not only induced hyperglycemia in Wistar rats but also developed diabetic nephropathy (DN). However, lycopene was found effective in relieving the biochemical symptoms of DN. Thus lycopene provides protection against development of diabetic nephropathy and ameliorates renal function by halting AGE-RAGE axis. © 2015 BioFactors, 41(5):372-381, 2015. [ABSTRACT FROM AUTHOR]

Abstract: Glycation of biomolecules leads to the establishment of advanced glycation end products (AGEs), which have significant role in the pathophysiology of diabetes leading to disorders, such as atherosclerosis. Ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the glycation reactions in vivo, however, no report has been published to discuss d-ribose induced glycation of low density lipoprotein (LDL). The present study initially focuses on the glycation of commercially available LDL using different concentrations of d-ribose for varied incubation time intervals. The structural perturbations induced in LDL were analyzed by UV–vis, fluorescence & circular dichroism spectroscopy, and thermal denaturation studies. The ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. We report structural perturbations, increased carbonyl content, ketoamine moieties and HMF content in d-ribose induced glycated LDL (LDL-AGEs) as compared to native analogue. These results provide evidence that LDL-AGEs could interfere in normal physiological functions and might contribute in the initiation of diabetes induced atherosclerosis and other secondary cardiovascular problems in diabetic patients. Though ours is a preliminary study, we are sure it would open the topic for further studies. [Copyright &y& Elsevier]

The process of glycation, characterized by the non-enzymatic reaction between sugars and free amino groups on biomolecules, is a key contributor to the development and progression of both microvascular and macrovascular complications associated with diabetes, particularly due to persistent hyperglycemia. This glycation process gives rise to advanced glycation end products (AGEs), which play a central role in the pathophysiology of diabetes complications, including nephropathy. The d -ribose-mediated glycation of fibrinogen plays a central role in the pathogenesis of diabetes nephropathy (DN) and retinopathy (DR) by the generation and accumulation of advanced glycation end products (AGEs). Glycated fibrinogen with d -ribose (Rb-gly-Fb) induces structural changes that trigger an autoimmune response by generating and exposing neoepitopes on fibrinogen molecules. The present research is designed to investigate the prevalence of autoantibodies against Rb-gly-Fb in individuals with type 2 diabetes mellitus (T2DM), DN & DR. Direct binding ELISA was used to test the binding affinity of autoantibodies from patients' sera against Rb-gly-Fb and competitive ELISA was used to confirm the direct binding findings by checking the bindings of isolated IgG against Rb-gly-Fb and its native conformer. In comparison to healthy subjects, 32% of T2DM, 67% of DN and 57.85% of DR patients' samples demonstrated a strong binding affinity towards Rb-gly-Fb. Both native and Rb-gly-Fb binding by healthy subjects (HS) sera were non-significant (p > 0.05). Furthermore, the early, intermediate, and end products of glycation have been assessed through biochemical and physicochemical analysis. The biochemical markers in the patient groups were also significant (p < 0.05) in comparison to the HS group. This study not only establishes the prevalence of autoantibodies against d -ribose glycated fibrinogen in DN but also highlights the potential of glycated fibrinogen as a biomarker for the detection of DN and/or DR. These insights may open new avenues for research into novel therapeutic strategies and the prevention of diabetes-related nephropathy and retinopathy. [Display omitted] • Prevalence of autoantibodies against d -ribose glycated fibrinogen in type 2 diabetes mellitus (T2DM). • Glycation plays a critical role in generating an autoimmune response. • Ketoamines, protein carbonyls, TBARS, HMF, AGEs, and CML concentrations in patient sera were high. • Glycated fibrinogen might act as a biomarker for the early detection of diabetes-related diseases. [ABSTRACT FROM AUTHOR]

A nonenzymatic reaction between reducing sugars and amino groups of proteins results in the formation of advanced glycation end products, which are linked to a number of chronic progressive diseases with macro- and microvascular complications. In this research, we sought to ascertain the immunological response to d -ibose-glycated fibrinogen. New Zealand White female rabbits were immunized with native and d -ribose-glycated (Rb-gly-Fb) fibrinogen and used for studying the immunological response. Serum from these rabbits analyzed using direct binding and competitive inhibition ELISA was found to contain a high titer of antibodies against Rb-gly-Fb; Rb-gly-Fb was much more immunogenic than its native form. The IgG against Rb-gly-Fb (Rb-gly-Fb-IgG) was highly specific against the immunogenic protein. Moreover, histopathology and immunofluorescence studies revealed the deposition of the Rb-gly-Fb-IgG immune complex in the glomerular basement membrane of the kidneys of immunized rabbits. Furthermore, immunization with Rb-gly-Fb increased the expression of genes encoding proinflammatory cytokines, tumour necrosis factor α, interleukin-6, interleukin-1β, and interferon-gamma, which is indicative of increased inflammation and the antigenic role of Rb-gly-Fb in provoking an immune response. • Fibrinogen because of glycation results in the structural perturbations. • Fibrinogen protein becomes highly immunogenic after the glycation reaction. • Immunogenicity of the Fibrinogen is due to the formation of neo-epitopes in its structure. [ABSTRACT FROM AUTHOR]

Abstract: The non-enzymatic addition of carbonyl group of sugar moiety to the amino group of DNA macromolecule leads to the formation of early glycation products (Amadori products) which undergoes rearrangement, cyclization and dehydration to form advanced glycation end products (AGEs). While the formation of glucose derived glycated DNA has been previously demonstrated, however no extensive studies have been performed to assess the glycation of DNA using d-ribose as glycating agent. d-ribose, an important monosaccharide, is a highly reactive pentose sugar which results in the rapid formation of AGEs. To the best of our knowledge, this is the first study to characterize the d-ribose-induced changes in calf thymus DNA, as well as calf thymus DNA Amadori and calf thymus DNA-AGEs. The main objective of the study is to investigate the non-enzymatic glycation of calf thymus DNA by using different concentrations of d-ribose at increasing time period. The obtained Amadori products, AGEs were characterized with respect to the extent of DNA strand break and base modifications. Additionally, their nitroblue tetrazolium (NBT) reduction assay, absorbance, agarose gel electrophoresis, fluorescence, circular dichroism (CD) and thermal denaturation (T m) characteristics were extensively studied. We found significant changes in the modification of DNA and in AGE-specific fluorescence, using different concentration of modifiers (d-ribose). The results provide the mechanistic insight of d-ribose induced glycation in calf thymus DNA. The bio-availability of d-ribose makes this carbonyl species quite reactive and damaging, therefore having direct implication in diabetes. This is the preliminary study done on d-ribose glycation and warrants further study to probe the role ribose-DNA glycation in different disease state including diabetes. [Copyright &y& Elsevier]

Non-enzymatic protein glycation results in the formation of advanced glycation end products (AGEs) leads to the pathogenesis of long-term diabetic complications. Iridin (ID), an antioxidant, plays an important role in protecting against oxidative stress and could therefore be an efficacious anti-glycating regimen. Herein, we assessed the anti-glycating potential of ID against d -ribose induced glycation of bovine serum albumin (BSA) by various biophysical and biochemical techniques. Our results from several physicochemical assays advocated that ID was able to evidently prevent the AGEs generation via reducing hyperchromicity, early glycation products (EGPs), carbonyl content (CC), hydroxymethyl furfural (HMF) content, production of fluorescent AGEs, protection against loss of secondary structure (i.e. α-helix and β-sheets) of proteins, increasing the free lysine and free arginine content, reduced binding of congo red (CR), and reduced thioflavin T (ThT) and 8-aninilo-1-napthalene sulphonate (ANS)-specific fuorescence in glycated-BSA (Gly-BSA). On the basis of these findings, we concluded that ID possesses the significant anti-glycation potential and may be established as a remarkable anti-AGEs therapeutic agent. Further in-vivo and clinical studies are still warranted to uncover the therapeutic effects of ID against age-related as well as metabolic diseases. [ABSTRACT FROM AUTHOR]