The Impact of Thermal Treatment and In Vitro Digestion on Antioxidant Activity and Anti‐Glycation Properties of Antioxidant Crude Extract From Hot and Cold Brew Spent Coffee Ground

Oxidative stress, hyper-inflammatory responses, and protein glycation are the chief contributing factors in the pathogenesis of several diseases. This study aimed to explore the therapeutic role of myrrh in health management through in vitro and in silico studies. Antioxidant potential, anti-inflammatory potential, antiglycation, and advanced glycation end products (AGEs) formation inhibition activities were determined by various in vitro assays. Molecular docking was performed to predict the non-covalent binding of macromolecules (receptor) and a small molecule (ligand). Myrrh extract contained significant antioxidant activity as reflected by FRAP value (16.12 µg ascorbic acid/100 mg dry weight), the maximum percentage of DPPH scavenging (57.71%), and maximum hydrogen peroxide reducing activity (58.71%) at a concentration of 600 µg/mL. Further, the extract exhibited maximum protection from bovine serum albumin (BSA) denaturation inhibition (53.47%), anti-proteinase action (43.517%), and egg albumin denaturation inhibition (44.95%) at a dose of 600 µg/mL concentration. Myrrh is used in pharmacy as an antiseptic, anti-inflammatory, antimicrobial, antifungal, and anti-venom remedy. This study aimed to explore the antioxidant, anti-inflammatory, antiarthritic, antiglycation, and advanced glycation end products (AGEs) formation inhibition ability of methanolic myrrh extract. It was found that myrrh has good antioxidant potential due to plenty of flavonoids and polyphenolic compounds, as reflected by results of the 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) assay, FRAP (ferric reducing antioxidant power) test, and hydrogen peroxide reducing test. Furthermore, myrrh methanolic extract was found to be significantly effective against heat-induced albumin denaturation, and percent inhibition of denaturation increases with increased extract concentration. The presence of myrrh extract at a dose of 600 μg/mL decreased browning intensity (59.38%), percent aggregation index (59.88%), and percentage amyloid structure (56.13%). We used molecular docking tools to study the role of myrrh in oxidative stress (Catalase), antioxidant property (Superoxide dismutase), and antiviral property (spike protein S). The molecular docking analysis confirmed four phytoconstituents; 2,3-Furandione, Curzerene, delta-Elemene, and Furanoeudesma-1,3-Diene interact with catalase and superoxide dismutase. Curzerene and Furanoeudesma-1,3-Diene showed remarkable interaction with SARS-CoV-2 spike protein S. Our data suggest that myrrh resin extract can be used to develop a suitable alternative therapy for various diseases linked with oxidative stress, inflammation, glycation, and AGEs.

Alternative routes for the formation of glyceraldehyde-derived AGEs (TAGE) in vivo

SummaryThis study investigated the inhibitory effects of curcumin and piperine on fluorescent advanced glycation end products (fAGEs) formation in a bovine serum albumin (BSA)–fructose model. Model systems of BSA and fructose were prepared, and curcumin or piperine was added. fAGEs and BSA oxidation product (dityrosine, kynurenine and N'‐formylkynurenine) contents were determined. The results showed that fAGEs content decreased with increasing concentration of curcumin and piperine (P < 0.05). Addition of curcumin and piperine at 160 µg mL−1 could inhibit fluorescent AGEs by 100% and 93% respectively. Dityrosine and N'‐formylkynurenine contents decreased as curcumin and piperine concentration increased (P < 0.05). Furthermore, the result of principal component analysis indicated that curcumin and piperine markedly impeded BSA oxidation, resulting in a lower level of fAGEs in model systems. Therefore, adding curcumin and piperine may facilitate reduced fAGEs levels in BSA–fructose model.

Formation of advanced glycation end-products in silver carp (Hypophthalmichthys molitrix) surimi products during heat treatment as affected by freezing-thawing cycles

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

Cinnamon bark has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. In this study, the inhibitory effect of cinnamon bark on the formation of advanced glycation endproducts (AGEs) was investigated in a bovine serum albumin (BSA)-glucose model. Several phenolic compounds, such as catechin, epicatechin, and procyanidin B2, and phenol polymers were identified from the subfractions of aqueous cinnamon extract. These compounds showed significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal (MGO), an intermediate reactive carbonyl of AGE formation. Preliminary study on the reaction between MGO and procyanidin B2 revealed that MGO-procyanidin B2 adducts are primary products which are supposed to be stereoisomers. This is the first report that proanthocyanidins can effectively scavenge reactive carbonyl species and thus inhibit the formation of AGEs. As proanthocyanidins behave in a similar fashion as aminoguanidine (AG), the first AGE inhibitor explored in clinical trials, they show great potential to be developed as agents to alleviate diabetic complications.

The advanced stage of the glycation process (also called the "Maillard reaction") that leads to the formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients and in the aging process. AGEs elicit a wide range of cell-mediated responses that might contribute to diabetic complications, vascular disease, renal disease, and Alzheimer's disease. Recently, it has been proposed that AGE are not only created from glucose per se, but also from dicarbonyl compounds derived from glycation, sugar autoxidation, and sugar metabolism. However, this advanced stage of glycation is still only partially characterized and the structures of the different AGEs that are generated in vivo have not been completely determined. Because of their heterogeneity and the complexity of the chemical reactions involved, only some AGEs have been characterized in vivo, including N-carboxymethyllysine (CML), pentosidine, pyrraline, and crosslines. In this article, we provide a brief overview of the pathways of AGE formation and of the immunochemical methods for detection of AGEs, and we also provide direct immunological evidence for the existence of five distinct AGE classes (designated as AGE-1 to -5) within the AGE-modified proteins and peptides in the serum of diabetic patients on hemodialysis. We also propose pathways for the in vivo formation of various AGEs by glycation, sugar autoxidation, and sugar metabolism.

Ginsenoside derivatives inhibit advanced glycation end-product formation and glucose–fructose mediated protein glycation in vitro via a specific structure–activity relationship

Proteins undergo continuous changes under the action of various intrinsic and extrinsic factors, leading to alteration of several intracellular metabolic pathways and the development of various clinical disorders. Non-enzymatic glycosylation is one of the main factors responsible for the progression of diabetic complications and the aging process. Although there are currently many effective therapies in the prevention and treatment of these diseases, in the last decade, there has been an increasing trend of replacing synthetic drugs by natural compounds, in order to reduce the side effects that may occur and the production costs. It is well known that aspirin (acetylsalicylic acid) inhibits the glycation process of serum proteins by acetylating N-terminal amino groups and lysine residues in their structure. Therefore, the main purpose of our research was to analyze the non-enzymatic glycation and fructation process of hemoglobin through spectrometric and electrophoretic techniques, in order to reveal how this process could influence the three-dimensional structure and biological function of the protein, and the effect of some natural aspirin-like compounds on the peroxidase and esterase activity of hemoglobin during fructose and glucose binding. In this way, a preliminary phytochemical characterization of a bark extract of white willow (Salix alba) was performed in order to evaluate the content of total phenolics, flavonoids, and salicylic derivatives, as well as the antioxidant activity. Then, human erythrocytes isolated from whole peripheral blood were incubated with different concentrations of fructose/glucose (10, 50, 100 mM) and S. alba extract for 5, 7, 10 and 14 days. The results obtained from the THz spectra confirmed that fructose was more reactive than glucose, so the glycation process took place more slowly than fructation. Also, the presence of S. alba extract showed an antiglycosylating effect, but not a total inhibition of the glycation process. In addition, enzymatic determinations proved that willow bark extract restored the peroxidase and esterase activities to the control levels. Our data indicated that salicylic compounds can be successfully used as substitutes for aspirin, one of the main synthetic compounds with anti-inflammatory and anti-glycosylating roles. Salicin, salicylic acid and other salicylic compounds possess strong antioxidant properties, which give them the ability to participate in the glycosylation process to block the formation of advanced glycation end products (AGEs).

BackgroundMethylglyoxal (MG) is one of the most reactive glycating agents, which result the formation of advanced glycation end-products (AGEs) that have been implicated in the progression of age-related diseases. Inhibition of MG-induced AGE formation is the imperative approach for alleviating diabetic complications. The objective of this study was to investigate the MG-trapping abilities of herbal medicines and their inhibitory activities on the formation of MG-derived AGEs.MethodsThe aqueous extract of herbal medicines was measured for the content of total phenolic compounds and the antioxidant activity by Folin-Ciocalteu assay and the 1,1-diphenyl 2-picrylhydrazyl (DPPH) radical scavenging activity, respectively. The extracts were investigated the MG-trapping ability by high performance liquid chromatography (HPLC). The extracts were incubated with BSA and MG at 37 °C for 1 day. The formation of MG-derived AGEs was measured.ResultsTotal phenolic compounds of eleven herbal medicines showed marked variations, ranging from 12.16 to 272.36 mg gallic acid equivalents/g extract. All extracts (1 mg/mL) markedly exhibited the DPPH radical scavenging activity (0.31–73.52 %) and the MG-trapping abilities (13.97–58.97 %). In addition, they also inhibited the formation of MG-derived AGEs by 4.01–79.98 %. The results demonstrated that Rhinacanthus nasutus, Syzygium aromaticum, and Phyllanthus amarus were the potent inhibitors against the formation of MG-derived AGEs. The positive correlations between the contents of phenolics and % MG trapping (r = 0.912, p < 0.01) and % inhibition of MG-derived AGEs (r = 0.716, p < 0.01) were observed in the study. Furthermore, there was a moderate positive correlation between % MG trapping and % inhibition of MG-derived AGEs (r =0.584, p < 0.01).ConclusionsRhinacanthus nasutus, Syzygium aromaticum, and Phyllanthus amarus could reduce the formation of MG-derived AGEs through their MG-trapping abilities. These findings are relevant for focusing on potential herbal medicines to prevent or ameliorate AGE-mediated diabetic complications.

Evaluation of the in vitro inhibitory effects of buckwheat enhanced wheat bread extracts on the formation of advanced glycation end-products (AGEs)

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

Synthesis and evaluation of novel 2,3,5-triaryl-4H,2,3,3a,5,6,6a-hexahydropyrrolo[3,4-d]isoxazole-4,6-diones for advanced glycation end product formation inhibitory activity

Human and other biological tissues face a continual threat of damage by alpha-oxoaldehydes formed endogenously. Glyoxal, methylglyoxal and 3-deoxyglucosone are formed by the degradation of glycolytic intermediates, glycated proteins and lipid peroxidation. They are potent glycating agents of protein and nucleotides leading to the formation of advanced glycation endproducts (AGEs). With proteins, they are arginine residue-directed glycating agents forming mainly hydroimidazolones, found at 0.1-1% of total arginine residues in tissues (2-20% of proteins modified). With nucleotides, imidazopurinone- and N2-carboxyalkyl- derivatives of deoxyguanosine are formed, found at 0.1-0.8 per 10(6) nucleotides in DNA. Glycation occurs in all tissues and body fluids. Cellular proteolysis of AGE-modified proteins and DNA releases glycated amino acids and nucleosides. Glycated amino acids and nucleosides are released into plasma, undergo glomerular filtration and are excreted in urine. The damage to tissue protein and nucleotides by alpha-oxoaldehydes is suppressed by the metabolism of alpha-oxoaldehyde glycating agents by the glutathione-dependent enzyme, glyoxalase I, and aldo-keto reductases. These enzymatic activities are part of the enzymatic defence against glycation. Tissue damage by alpha-oxoaldehyde glycation is implicated in diabetic and non-diabetic vascular disease, renal failure, cirrhosis, Alzheimer's disease, arthritis and ageing.

Advanced glycation end products are major contributors to the pathology of diabetes, Alzheimer's disease, and atherosclerosis; accordingly, identification of antiglycation compounds is attracting considerable interest. In the present study, the inhibitory effect of gum arabic capped-silver nanoparticles on advanced glycation end products formation was monitored by several biophysical techniques. Silver nanoparticles were characterized by ultraviolet-visible, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Bovine serum albumin and methylglyoxal mixtures incubated with increasing concentrations of silver nanoparticles showed significant reductions in advanced glycation end product formation that were confirmed by ultraviolet-visible, fluorescence spectrometry, and high-performance liquid chromatography techniques. High-performance liquid chromatography showed decreased adduct formation of glycated protein in the presence of silver nanoparticles. The structural changes induced by silver nanoparticles were further confirmed by circular dichroism and Fourier transform infrared spectroscopy. Strong inhibition of advanced glycation end product formation was observed in the presence of elevated silver nanoparticles. The results of this study suggest that silver nanoparticles are a potent antiglycating agent.