Glycated nisin enhances nisin's cytotoxic effects on breast cancer cells.

Antimicrobial peptides, such as nisin, are proposed as promising agents for cancer treatment. While glycation has been recognized as an effective method for enhancing various physicochemical properties of nisin, its anticancer effects remain unexplored. Therefore, we aimed to assess the anticancer potential of glycated nisin against MDA-MB-231 cells. The MDA-MB cells were treated with increasing concentrations of nisin and glycated nisin for 24, 48, and 72 h. The IC50 values for nisin were higher than those for glycated nisin. Glycated nisin at concentrations of 20 and 40 µg/mL decreased cell viability more than nisin at the same concentrations. The rate of apoptosis in the group treated with 20 µg/mL of nisin was lower compared to other treatment groups, and no significant difference in apoptosis rates was observed at different time points (p > 0.05). However, in the glycated nisin groups with concentrations of 10, 20, and 40 µg/mL, the level of apoptosis was very high after 24 h (73-81% of cells undergoing apoptosis). Overall, our study suggests that glycated nisin exhibits stronger cytotoxic effects on MDA-MB-231 cells, primarily involving the induction of apoptosis. This indicates its potential utilization as an alternative approach to address the issue of drug resistance in cancer cells.

Potential of Sorghum Seeds in Alleviating Hyperglycemia, Oxidative Stress, and Glycation Damage.

Diabetes mellitus, characterized by dysregulated glucose metabolism, oxidative stress, and the formation of advanced glycation end products, poses a significant global health burden. In this study, we explored the potential of sorghum (Sorghum bicolor) seeds, known for their abundant phytochemical composition, as a natural remedy for diabetes and its associated damage. High-performance liquid chromatography/high-resolution mass spectrometry analysis revealed a remarkable phenolic richness in sorghum grains, including gallic acid, quercetin, and the predominant procyanidin B-1, with ecotype-specific variations in flavonoid distribution. Elemental analysis by ICP showed an abundance of macro-elements (Ca, K, Mg), trace elements (Fe, Mn, Si, Zn), and ultra-trace elements (B, Co, Cr, Cu, Mo, Se, V) essential for human health, supporting its therapeutic and nutritional potential. Additionally, the results demonstrated variable total phenolic contents (188-297 mg GAE/g dE) and total flavonoid contents (66-78 mg QE/g dE), with corresponding differences in antioxidant activities across the five ecotypes. Treatment with sorghum seed extract (SE1) significantly reduced oxidative stress markers, such as malondialdehyde (MDA)by 40% and hydrogen peroxide (H2O2) by 63%, in diabetic mice, compared to untreated diabetic controls. Moreover, sorghum extracts exhibited a remarkable increase in antioxidant enzyme activities, including a 50% increase in superoxide dismutase (SOD) activity and a 60% increase in glutathione peroxidase (GPx) activity, indicating their potential to bolster antioxidant defenses against diabetes-induced oxidative stress. These findings underscore the therapeutic potential of sorghum seeds in diabetes management and prevention, paving the way for the development of functional foods with enhanced health benefits.

Phloroglucinol inhibited glycation via entrapping carbonyl intermediates.

Advanced glycation end products (AGEs) play an important role in the pathogenesis of age-linked disorders and diabetes mellitus. The aim of this study was to assess the repurposing potential of Phloroglucinol (PHL the antispasmodic drug), as an anti-glycation agent using Fructose-BSA model. The ability of PHL to inhibit AGE formation was evaluated using AGEs formation (Intrinsic fluorescence), fructosamine adduct (NBT) and free lysine availability (TNBSA) assays. The BSA protein conformation was assessed through Thioflavin-T, Congo-Red and Circular Dichroism assays. The lysine blockade and carbonyl entrapment were explored as possible mode of action. Our data showed that PHL significantly decreased the formation of AGEs with an IC50 value of 0.3mM. The fructosamine adducts and free lysine load was found to be reduced. Additionally, the BSA conformation was preserved by PHL. Mechanistic assays did not reveal involvement of lysine blockade as underlying reason for reduction in AGEs load. This was also supported by computational data whereby PHL failed to engage any catalytic residue involved in early fructose-BSA interaction. However, it was found to entrap the carbonyl moieties. In conclusion, the PHL demonstrated anti-glycation potential, which can be attributed to its ability to entrap carbonyl intermediates. Hence, the clinically available antispasmodic drug, presents itself as a promising candidate to be repurposed as anti-glycation agent.

Attenuation of albumin glycation and oxidative stress by minerals and vitamins: An in vitro perspective of dual-purpose therapy.

Nonenzymatic glycation of proteins is accelerated in the context of elevated blood sugar levels in diabetes. Vitamin and mineral deficiencies are strongly linked to the onset and progression of diabetes. The antiglycation ability of various water- and fat-soluble vitamins, along with trace minerals like molybdenum (Mo), manganese (Mn), magnesium (Mg), chromium, etc., have been screened using Bovine Serum Albumin (BSA) as in vitro model. BSA was incubated with methylglyoxal (MGO) at 37 °C for 48 h, along with minerals and vitamins separately, along with controls and aminoguanidine (AG) as a standard to compare the efficacy of the minerals and vitamins. Further, their effects on renal cells' (HEK-293) antioxidant potential were examined. Antiglycation potential is measured by monitoring protein glycation markers, structural and functional modifications. Some minerals, Mo, Mn, and Mg, demonstrated comparable inhibition of protein-bound carbonyl content and ß-amyloid aggregation at maximal physiological concentrations. Mo and Mg protected the thiol group and free amino acids and preserved the antioxidant potential. Vitamin E, D, B1 and B3 revealed significant glycation inhibition and improved antioxidant potential in HEK-293 cells as assessed by estimating lipid peroxidation, SOD and glyoxalase activity. These results emphasize the glycation inhibitory potential of vitamins and minerals, indicating the use of these micronutrients in the prospect of the therapeutic outlook for diabetes management.

N-Glycan profile of the cell membrane as a probe for lipopolysaccharide-induced microglial neuroinflammation uncovers the effects of common fatty acid supplementation.

Altered N-glycosylation of proteins on the cell membrane is associated with several neurodegenerative diseases. Microglia are an ideal model for studying glycosylation and neuroinflammation, but whether aberrant N-glycosylation in microglia can be restored by diet remains unknown. Herein, we profiled the N-glycome, proteome, and glycoproteome of the human microglia following lipopolysaccharide (LPS) induction to probe the impact of dietary and gut microbe-derived fatty acids-oleic acid, lauric acid, palmitic acid, valeric acid, butyric acid, isobutyric acid, and propionic acid-on neuroinflammation using liquid chromatography-tandem mass spectrometry. LPS changed N-glycosylation in the microglial glycocalyx altering high mannose and sialofucosylated N-glycans, suggesting the dysregulation of mannosidases, fucosyltransferases, and sialyltransferases. The results were consistent as we observed the restoration effect of the fatty acids, especially oleic acid, on the LPS-treated microglia, specifically on the high mannose and sialofucosylated glycoforms of translocon-associated proteins, SSRA and SSRB along with the cell surface proteins, CD63 and CD166. In addition, proteomic analysis and in silico modeling substantiated the potential of fatty acids in reverting the effects of LPS on microglial N-glycosylation. Our results showed that N-glycosylation is likely affected by diet by restoring alterations following LPS challenge, which may then influence the disease state.

Artificial and Natural Sweeteners Biased T1R2/T1R3 Taste Receptors Transactivate Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition of Metastatic Phenotype.

Understanding the role of biased taste T1R2/T1R3 G protein-coupled receptors (GPCR) agonists on glycosylated receptor signaling may provide insights into the opposing effects mediated by artificial and natural sweeteners, particularly in cancer and metastasis. Sweetener-taste GPCRs can be activated by several active states involving either biased agonism, functional selectivity, or ligand-directed signaling. However, there are increasing arrays of sweetener ligands with different degrees of allosteric biased modulation that can vary dramatically in binding- and signaling-specific manners. Here, emerging evidence proposes the involvement of taste GPCRs in a biased GPCR signaling crosstalk involving matrix metalloproteinase-9 (MMP-9) and neuraminidase-1 (Neu-1) activating glycosylated receptors by modifying sialic acids. The findings revealed that most natural and artificial sweeteners significantly activate Neu-1 sialidase in a dose-dependent fashion in RAW-Blue and PANC-1 cells. To confirm this biased GPCR signaling crosstalk, BIM-23127 (neuromedin B receptor inhibitor, MMP-9i (specific MMP-9 inhibitor), and oseltamivir phosphate (specific Neu-1 inhibitor) significantly block sweetener agonist-induced Neu-1 sialidase activity. To assess the effect of artificial and natural sweeteners on the key survival pathways critical for pancreatic cancer progression, we analyzed the expression of epithelial-mesenchymal markers, CD24, ADLH-1, E-cadherin, and N-cadherin in PANC-1 cells, and assess the cellular migration invasiveness in a scratch wound closure assay, and the tunneling nanotubes (TNTs) in staging the migratory intercellular communication. The artificial and natural sweeteners induced metastatic phenotype of PANC-1 pancreatic cancer cells to promote migratory intercellular communication and invasion. The sweeteners also induced the downstream NFκB activation using the secretory alkaline phosphatase (SEAP) assay. These findings elucidate a novel taste T1R2/T1R3 GPCR functional selectivity of a signaling platform in which sweeteners activate downstream signaling, contributing to tumorigenesis and metastasis via a proposed NFκB-induced epigenetic reprogramming modeling.

Effects of myricetin and its derivatives on nonenzymatic glycation: A mechanism study based on proteomic modification and fluorescence spectroscopy analysis.

Myricetin and its derivatives, myricitrin and dihydromyricetin, are flavonoids widely presented in foods and phytomedicine that possess tremendous health potential. In this study, we compared the antiglycation activity of myricetin and its derivatives, then investigated the underlying mechanism using proteomic modification and fluorescence spectroscopy analysis. All three compounds exhibited thorough inhibition on nonenzymatic glycation process, with the inhibitory effects on AGEs reaching 85% at 40 µmol/L. They effectively protected bovine serum albumin (BSA) structure by inhibiting protein oxidation, preventing the conversion from α-helix to ß-sheet, and reducing amyloid-like cross-ß structure formation. Among the three compounds, myricetin showed a predominant antiglycation activity. Proteomic analysis identified the early glycated sites that were protected by myricetin, including lysine K235, 256, 336, 421, 420, 489, etc. Additionally, fluorescence spectroscopy revealed spontaneous interactions between BSA and myricetin. Overall, myricetin holds promise as an antiglycation agent in both the food and drug industries.

Inhibitory effect of organogermanium compound 3-(trihydroxygermyl)propanoic acid on fructose-induced glycation of amino compounds.

3-(Trihydroxygermyl)propanoic acid (THGP), a hydrolysate of poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132, also known as repagermanium), can inhibit glycation between glucose/ribose and amino compounds. In addition, THGP may inhibit glycation by inhibiting reactions that occur after Amadori rearrangement and inducing the reversible solubilization of AGEs. In this study, we first investigated the effects and mechanisms on the glycation of fructose and amino compounds by THGP, as a greater reactivity was obtained with fructose than with glucose. Unlike other anti-glycation materials, THGP can form a complex with fructose, the initial compound of glycation. THGP also inhibited the production of AGEs and suppressed the reduction of fructose in a reaction between fructose and arginine. These results indicate that THGP forms a complex with cyclic fructose possessing a cis-diol structure at a reducing end, and that it suppresses the ring-opening of fructose and the progress of the initial glycation reaction. We next tried to evaluate the suppressive effect of glucosyl hesperidin (GHes) and THGP on the reaction of glycation between fructose and collagen. Both compounds effectively reduced the production of AGEs individually, and the combination of them led to a synergistic suppression. Therefore, through combination with other antiglycation materials, THGP may cooperatively exhibit glycation-inhibitory effects and be able to suppress the AGE production.

Modulatory effects of rutin and vitamin A on hyperglycemia induced glycation, oxidative stress and inflammation in high-fat-fructose diet animal model.

In the current study we investigated the impact of combination of rutin and vitamin A on glycated products, the glyoxalase system, oxidative markers, and inflammation in animals fed a high-fat high-fructose (HFFD) diet. Thirty rats were randomly divided into six groups (n = 5). The treatments, metformin (120 mg/kg), rutin (100 mg/kg), vitamin A (43 IU/kg), and a combination of rutin (100 mg/kg) and vitamin A (43 IU/kg) were given to relevant groups of rats along with high-fructose high-fat diet for 42 days. HbA1c, D-lactate, Glyoxylase-1, Hexokinase 2, malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT), nuclear transcription factor-B (NF-κB), interleukin-6 (IL-6), interleukin-8 (IL-8) and histological examinations were performed after 42 days. The docking simulations were conducted using Auto Dock package. The combined effects of rutin and vitamin A in treated rats significantly (p < 0.001) reduced HbA1c, hexokinase 2, and D-lactate levels while preventing cellular damage. The combination dramatically (p < 0.001) decreased MDA, CAT, and GPx in treated rats and decreased the expression of inflammatory cytokines such as IL-6 andIL-8, as well as the transcription factor NF-κB. The molecular docking investigations revealed that rutin had a strong affinity for several important biomolecules, including as NF-κB, Catalase, MDA, IL-6, hexokinase 2, and GPx. The results propose beneficial impact of rutin and vitamin A as a convincing treatment strategy to treat AGE-related disorders, such as diabetes, autism, alzheimer's, atherosclerosis.

Glucosamine and Silibinin Alter Cartilage Homeostasis through Glycosylation and Cellular Stresses in Human Chondrocyte Cells.

Osteoarthritis is more prevalent than any other form of arthritis and is characterized by the progressive mechanical deterioration of joints. Glucosamine, an amino monosaccharide, has been used for over fifty years as a dietary supplement to alleviate osteoarthritis-related discomfort. Silibinin, extracted from milk thistle, modifies the degree of glycosylation of target proteins, making it an essential component in the treatment of various diseases. In this study, we aimed to investigate the functional roles of glucosamine and silibinin in cartilage homeostasis using the TC28a2 cell line. Western blots showed that glucosamine suppressed the N-glycosylation of the gp130, EGFR, and N-cadherin proteins. Furthermore, both glucosamine and silibinin differentially decreased and increased target proteins such as gp130, Snail, and KLF4 in TC28a2 cells. We observed that both compounds dose-dependently induced the proliferation of TC28a2 cells. Our MitoSOX and DCFH-DA dye data showed that 1 µM glucosamine suppressed mitochondrial reactive oxygen species (ROS) generation and induced cytosol ROS generation, whereas silibinin induced both mitochondrial and cytosol ROS generation in TC28a2 cells. Our JC-1 data showed that glucosamine increased red aggregates, resulting in an increase in the red/green fluorescence intensity ratio, while all the tested silibinin concentrations increased the green monomers, resulting in decreases in the red/green ratio. We observed increasing subG1 and S populations and decreasing G1 and G2/M populations with increasing amounts of glucosamine, while increasing amounts of silibinin led to increases in subG1, S, and G2/M populations and decreases in G1 populations in TC28a2 cells. MTT data showed that both glucosamine and silibinin induced cytotoxicity in TC28a2 cells in a dose-dependent manner. Regarding endoplasmic reticulum stress, both compounds induced the expression of CHOP and increased the level of p-eIF2α/eIF2α. With respect to O-GlcNAcylation status, glucosamine and silibinin both reduced the levels of O-GlcNAc transferase and hypoxia-inducible factor 1 alpha. Furthermore, we examined proteins and mRNAs related to these processes. In summary, our findings demonstrated that these compounds differentially modulated cellular proliferation, mitochondrial and cytosol ROS generation, the mitochondrial membrane potential, the cell cycle profile, and autophagy. Therefore, we conclude that glucosamine and silibinin not only mediate glycosylation modifications but also regulate cellular processes in human chondrocytes.

D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG).

INTRODUCTION: Fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG) is a rare autosomal recessive inborn error of metabolism characterized by a decreased flux through the salvage pathway of GDP-fucose biosynthesis due to a block in the recycling of L-fucose that exits the lysosome. FCSK-CDG has been described in 5 individuals to date in the medical literature, with a phenotype comprising global developmental delays/intellectual disability, hypotonia, abnormal myelination, posterior ocular disease, growth and feeding failure, immune deficiency, and chronic diarrhea, without clear therapeutic recommendations. PATIENT AND METHODS: In a so far unreported FCSK-CDG patient, we studied proteomics and glycoproteomics in vitro in patient-derived fibroblasts and also performed in vivo glycomics, before and after treatment with either D-Mannose or L-Fucose. RESULTS: We observed a marked increase in fucosylation after D-mannose supplementation in fibroblasts compared to treatment with L-Fucose. The patient was then treated with D-mannose at 850 mg/kg/d, with resolution of the chronic diarrhea, resolution of oral aversion, improved weight gain, and observed developmental gains. Serum N-glycan profiles showed an improvement in the abundance of fucosylated glycans after treatment. No treatment-attributed adverse effects were observed. CONCLUSION: D-mannose is a promising new treatment for FCSK-CDG.

Liposome-encapsulated mannose-1-phosphate therapy improves global N-glycosylation in different congenital disorders of glycosylation.

Phosphomannomutase 2 (PMM2) converts mannose-6-phospahate to mannose-1-phosphate; the substrate for GDP-mannose, a building block of the glycosylation biosynthetic pathway. Pathogenic variants in the PMM2 gene have been shown to be associated with protein hypoglycosylation causing PMM2-congenital disorder of glycosylation (PMM2-CDG). While mannose supplementation improves glycosylation in vitro, but not in vivo, we hypothesized that liposomal delivery of mannose-1-phosphate could increase the stability and delivery of the activated sugar to enter the targeted compartments of cells. Thus, we studied the effect of liposome-encapsulated mannose-1-P (GLM101) on global protein glycosylation and on the cellular proteome in skin fibroblasts from individuals with PMM2-CDG, as well as in individuals with two N-glycosylation defects early in the pathway, namely ALG2-CDG and ALG11-CDG. We leveraged multiplexed proteomics and N-glycoproteomics in fibroblasts derived from different individuals with various pathogenic variants in PMM2, ALG2 and ALG11 genes. Proteomics data revealed a moderate but significant change in the abundance of some of the proteins in all CDG fibroblasts upon GLM101 treatment. On the other hand, N-glycoproteomics revealed the GLM101 treatment enhanced the expression levels of several high-mannose and complex/hybrid glycopeptides from numerous cellular proteins in individuals with defects in PMM2 and ALG2 genes. Both PMM2-CDG and ALG2-CDG exhibited several-fold increase in glycopeptides bearing Man6 and higher glycans and a decrease in Man5 and smaller glycan moieties, suggesting that GLM101 helps in the formation of mature glycoforms. These changes in protein glycosylation were observed in all individuals irrespective of their genetic variants. ALG11-CDG fibroblasts also showed increase in high mannose glycopeptides upon treatment; however, the improvement was not as dramatic as the other two CDG. Overall, our findings suggest that treatment with GLM101 overcomes the genetic block in the glycosylation pathway and can be used as a potential therapy for CDG with enzymatic defects in early steps in protein N-glycosylation.

Coffee leaf extract inhibits advanced glycation end products and their precursors: A mechanistic study.

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.

Doxorubicin induces deglycosylation of cancer cell-intrinsic PD-1 by NGLY1.

Tumor cells can express the immune checkpoint protein programmed death-1 (PD-1), but how cancer cell-intrinsic PD-1 is regulated in response to cellular stresses remains largely unknown. Here, we uncover a unique mechanism by which the chemotherapy drug doxorubicin (Dox) regulates cancer cell-intrinsic PD-1. Dox upregulates PD-1 mRNA while reducing PD-1 protein levels in tumor cells. Although Dox shortens the PD-1 half-life, it fails to directly induce PD-1 degradation. Instead, we observe that Dox promotes the interaction between peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase (NGLY1) and PD-1, facilitating NGLY1-mediated PD-1 deglycosylation and destabilization. The maintenance of PD-1 sensitizes tumor cells to Dox-mediated antiproliferative effects. Our study unveils a regulatory mechanism of PD-1 in response to Dox and highlights a potential role of cancer cell-intrinsic PD-1 in Dox-mediated antitumor effects.

Suppression of N-Glycosylation of Zinc Finger Protein 471 Affects Proliferation, Invasion, and Docetaxel Sensitivity of Tongue Squamous Cell Carcinoma via Regulation of c-Myc.

Zinc finger protein 471 (ZNF471) is a member of the Krüppel-related domain zinc finger protein family, and has recently attracted attention because of its anti-cancer effects. N-glycosylation regulates expression and functions of the protein. This study aimed to investigate the effects of ZNF471 N-glycosylation on the proliferation, invasion, and docetaxel sensitivity of tongue squamous cell carcinoma (TSCC). It analyzed the expression, function, and prognostic significance of ZNF471 in TSCC using bioinformatics techniques such as gene differential expression analysis, univariate Cox regression analysis, functional enrichment analysis, and gene set enrichment analysis. Using site-specific mutagenesis, this study generated three mutant sites for ZNF471 N-glycosylation to determine the effect of N-glycosylation on ZNF471 protein levels and function. Quantitative real-time PCR, Western blot analysis, and immunohistochemistry tests confirmed the down-regulation of ZNF471 expression in TSCC. Low expression of ZNF471 is associated with poor prognosis of patients with TSCC. Overexpression of ZNF471 in vitro retarded the proliferation of TSCC cells and suppressed cell invasion and migration ability. Asparagine 358 was identified as a N-glycosylation site of ZNF471. Suppressing N-glycosylation of ZNF471 enhanced the protein stability and promoted the translocation of protein to the cell nucleus. ZNF471 binding to c-Myc gene promoter suppressed oncogene c-Myc expression, thereby playing the anti-cancer effect and enhancing TSCC sensitivity to docetaxel. In all, N-glycosylation of ZNF471 affects the proliferation, invasion, and docetaxel sensitivity of TSCC via regulation of c-Myc.

Protective effects of sugarcane polyphenol against UV-B-induced photoaging in Balb/c mouse skin: Antioxidant, anti-inflammatory, and anti-glycosylation Effects.

Although the benefits of sugarcane polyphenol (SP) are well documented, its function in preventing photoaging has not yet been investigated. This study aimed to investigate the protective effects of SP in preventing ultraviolet (UV)-B-induced skin photoaging in Balb/c mice, as well as the underlying mechanism. Chlorogenic acid was determined to be the primary component of SP by using high-performance liquid chromatography-mass spectrometry. SP and chlorogenic acid were orally administrated to mice for 56 days, and UV-B radiation exposure was administered 14 days after SP and chlorogenic acid administration and lasted 42 days to cause photoaging. SP and chlorogenic acid administrations significantly alleviated the UV-B-induced mouse skin photoaging, as indicated by the decrease in epidermal thickness, increase in the collagen (COL) volume fraction, and elevation in type 1 and type 3 COL contents. Notably, both SP and chlorogenic acid effectively reversed the overexpression of matrix metalloproteinase induced by UV-B exposure in the mouse skin. Furthermore, SP and chlorogenic acid reduced the expression of receptor for advanced glycosylation end products in the mice; amplified the activities of antioxidant enzymes superoxide dismutase and catalase; reduced malondialdehyde levels; and decreased inflammatory cytokines interleukin 1ß, interleukin 6, and tumor necrosis factor α levels. SP could be a prospective dietary supplement for anti-photoaging applications due to its antioxidant, anti-inflammatory, and anti-glycosylation attributes, and chlorogenic acid might play a major role in these effects. PRACTICAL APPLICATION: This study can provide a scientific basis for the practical application of sugarcane polyphenols. We expect that sugarcane polyphenols can be used in food and beverage products to provide flavor while combating skin aging.

Antiglycating Effects of Spirulina platensis Aqueous Extract on Glucose-Induced Glycation of Bovine Serum Albumin.

Glucose, the predominant carbohydrate in the human body, initiates nonenzymatic reactions in hyperglycemia, potentially leading to adverse biochemical interactions. This study investigates the interaction between glucose and Bovine Serum Albumin (BSA), along with the protective effects of Spirulina platensis PCC 7345 aqueous extract. Phycobiliproteins (phycocyanin, phycoerythrin, and allophycocyanin) in the extract were quantified using spectrophotometry. The extract's anti-glycation potential was assessed by analyzing its effects on albumin glycation, fluorescent advanced glycation end products (AGEs), thiol group oxidation, and ß-amyloid structure generation. Additionally, its antidiabetic potential was evaluated by measuring α-amylase and α-glucosidase enzyme inhibition. Results indicate that the Spirulina extract significantly mitigated ketoamine levels, fluorescence, and protein-carbonyl production induced by glucose, demonstrating a 67.81 % suppression of AGE formation after 28 days. Moreover, it effectively inhibited amyloid formation in BSA cross-linkages. These findings suggest the potential of S. platensis as an anti-glycation and antidiabetic agent, supporting its consideration for dietary inclusion to manage diabetes and associated complications.

Potential inhibitory effect of highland barley protein hydrolysates on the formation of advanced glycation end-products (AGEs): A mechanism study.

Advanced glycation end products (AGEs) can be caused during a glycoxidation reaction. This reaction is associated with complications of diabetes and the consequences of health problems. Therefore, we are exploring the prohibitory effect of highland barley protein hydrolysates (HBPHs) on AGE formation. Herein, first extracted the protein from highland barley with various pH conditions and then hydrolyzed using four different proteolytic enzymes (flavourzyme, trypsin, papain, pepsin) under different degrees of hydrolysis. We assessed three degrees of hydrolysates (lowest, middle, highest) of enzymes used to characterize the antioxidant activity and physicochemical properties. Among all the hydrolysates, flavourzyme-treated hydrolysates F-1, F-2, and F-3 indicated the high ability to scavenge DPPH (IC50 values of 0.97 %, 0.63 %, and 0.90 %), structural and functional properties. Finally, the inhibitory effect of the most active hydrolysates F-1, F-2, and F-3 against the AGEs formation was evaluated in multiple glucose-glycated bovine serum albumin (BSA) systems. Additionally, in a BSA system, F-3 exhibited the strong antiglycation activity, effectively suppressed the non-fluorescent AGE (CML), and the fructosamine level. Moreover, it decreased carbonyl compounds while also preventing the loss of thiol groups. Our results would be beneficial in the application of the food industry as a potential antiglycation agent for several chronic diseases.

Fatty acids characterisation by GC-MS, antiglycation effect at multiple stages and protection of erythrocytes cells from oxidative damage induced by glycation of albumin of Opuntia ficus-indica (L.) Mill seed oil cultivated in Eastern Morocco: Experimental and computational approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia ficus-indica (L.) Mill is frequently observed in the Moroccan traditional medicinal system, where these approaches are employed to mitigate the onset of diabetes and the subsequent complications it may entail. AIM OF THE STUDY: The aim of this research was to examine the effectiveness of Opuntia ficus-indica seed oil in preventing diabetic complications. Specifically, the study assessed its ability to counteract glycation at various stages, protected red blood cells from the harmful effects of glycated albumin, and inhibited pancreatic lipase digestive enzymes to understand its potential antihyperglycemic properties. Additionally, the study aimed to identify the chemical components responsible for these effects, evaluate antioxidant and anti-inflammatory properties, and conduct computational investigations such as molecular docking. MATERIALS AND METHODS: The assessement of Opuntia ficus-indica seed oil antiglycation properties involved co-incubating the extract oil with a bovine serum albumin-glucose glycation model. The study investigated various stages of glycation, incorporating fructosamine (inceptive stage), protein carbonyls (intermediate stage), and AGEs (late stage). Additionally, measurement of ß-amyloid aggregation of albumin was performed using Congo red, which is specific to amyloid structures. Additionally, the evaluation of oil's safeguarding effect on erythrocytes against toxicity induced by glycated albumin included the measurement of erythrocyte hemolysis, lipid peroxidation, reduced glutathione. The fatty acid of Opuntia ficus-indica seed oil were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The in vitro evaluation of antihyperglycemic activity involved the use of pancreatic lipase enzyme, while the assessement of antioxidant capability was carried out through the utilization of the ABTS and FRAP methods. The in vitro assessement of the denaturation of albumin activity was also conducted. In conjunction with the experimental outcomes, computational investigations were undertaken, specifically employing ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. Furthermore, molecular docking was utilized to predict antioxidant and antiglycation mechanisms based on protein targets. RESULTS: In vitro glycation assays, Opuntia ficus-indica seed oil displayed targeted inhibitory effects at multiple distinct stages. Within erythrocytes, in addition to mitigating hemolysis and lipid peroxidation induced by glycated albumin. GC-MS investigation revealed a richness of fatty acids and the most abundant compounds are Linoleic acid (36.59%), Palmitic acid (20.84%) and Oleic acid (19.33%) respectively. The findings of antioxidant ability showed a remarkable activity on FRAP and ABTS radicals. This oil showed a pronounced inhibitory impact (p < 0.001) on pancreatic lipase enzyme. It also exerted a notibale inhibition of albumin denaturation, in vitro. CONCLUSION: The identified results were supported by the abundant compounds of fatty acids unveiled through GC-MS analysis, along with the computational investigation and molecular docking.

Elucidation of inhibitory effects of bioactive anthraquinones towards formation of DNA advanced glycation end products (DNA-AGEs).

DNA is essential in biological processes as it directs transcription and translation assisting in RNA and protein synthesis. Extended periods of elevated blood glucose levels cause non-enzymatic DNA glycation, which results in the formation of DNA-AGEs and the production of free radicals, causing structural perturbation of DNA. In this work, we have investigated the glycation of calf thymus (ct-DNA) DNA and examined its inhibition by two anthraquinone derivatives, purpurin and aloin. Ribose sugar served as the glycating agent inducing non-enzymatic glycation of DNA and subsequent DNA-AGEs formation. UV-vis and fluorescence spectroscopic methods were utilized to characterize DNA-AGE formation in vitro. Circular dichroism (CD) spectroscopy was used to observe the structural disruption of DNA caused by glycation. The changes in AGEs fluorescence intensity and melting temperature (Tm) were measured to assess the inhibition of glycation process by aloin and purpurin. These derivatives demonstrated inhibitory effects via binding to glycating sites of ct-DNA or by scavenging free radicals generated during glycation. The current study elucidates the inhibitory actions of aloin and purpurin on DNA glycation, suggesting their possible applications in mitigating the adverse consequences linked to increased ribose concentrations.