The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental...The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.展开更多
Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an...Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.展开更多
Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms,including gallbladder cancer.In this regard,data de...Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms,including gallbladder cancer.In this regard,data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products(RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu,thus supporting tumor growth and development.AGEs are formed in biological systems or foods,and food-derived AGEs,also known as dietary AGEs are known to contribute to the systemic pool of AGEs.Once they bind to RAGE,the activation of multiple and crucial signaling pathways are triggered,thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration.In the present review,we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer,and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.展开更多
BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted me...BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(ε)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.展开更多
Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products(RAGE)in orchestrating a plethora of proinflammat...Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products(RAGE)in orchestrating a plethora of proinflammatory cellular responses leading to many of the complications and end-organ damages reported in patients with diabetes mellitus(DM).During the coronavirus disease 2019(COVID-19)pandemic,many clinical reports have pointed out that DM increases the risk of COVID-19 complications,hospitalization requirements,as well as the overall severe acute respiratory syndrome coronavirus 2 case-fatality rate.In the present review,we intend to focus on how the basal activation state of the RAGE axis in common preexisting conditions in DM patients such as endothelial dysfunction and hyperglycemia-related prothrombotic phenotype,as well as the contribution of RAGE signaling in lung inflammation,may then lead to the increased mortality risk of COVID-19 in these patients.Additionally,the crosstalk between the RAGE axis with either another severe acute respiratory syndrome coronavirus 2 receptor molecule different of angiotensin-converting enzyme 2 or the renin-angiotensin system imbalance produced by viral infection,as well as the role of this multi-ligand receptor on the obesity-associated lowgrade inflammation in the higher risk for severe illness reported in diabetes patients with COVID-19,are also discussed.展开更多
Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods...Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods that covers the entire range of food categories,which limits the accurate risk assessment of dietary AGEs in human diseases.In this study,we first established an isotope dilution UHPLCQq Q-MS/MS-based method for simultaneous quantification of 10 major AGEs in foods.The contents of these AGEs were detected in 334 foods covering all main groups consumed in Western and Chinese populations.Nε-Carboxymethyllysine,methylglyoxal-derived hydroimidazolone isomers,and glyoxal-derived hydroimidazolone-1 are predominant AGEs found in most foodstuffs.Total amounts of AGEs were high in processed nuts,bakery products,and certain types of cereals and meats(>150 mg/kg),while low in dairy products,vegetables,fruits,and beverages(<40 mg/kg).Assessment of estimated daily intake implied that the contribution of food groups to daily AGE intake varied a lot under different eating patterns,and selection of high-AGE foods leads to up to a 2.7-fold higher intake of AGEs through daily meals.The presented AGE database allows accurate assessment of dietary exposure to these glycotoxins to explore their physiological impacts on human health.展开更多
Type 2 diabetes mellitus(T2D)is an increasingly prevalent disease with numerous comorbidities including many in the spine.T2D is strongly linked with vertebral fractures,intervertebral disc(IVD)degeneration,and severe...Type 2 diabetes mellitus(T2D)is an increasingly prevalent disease with numerous comorbidities including many in the spine.T2D is strongly linked with vertebral fractures,intervertebral disc(IVD)degeneration,and severe chronic spinal pain.Yet the causative mechanism for these musculoskeletal impairments remains unclear.The chronic hyperglycemic state in T2D promotes the formation of advanced glycation end-products(AGEs)in tissues,and the accumulation of AGEs may play a role in musculoskeletal complications by modifying the extracellular matrix,impairing cellular homeostasis,and perpetuating an inflammatory cascade via its receptor(RAGE).The AGE and RAGE associated alterations in extracellular matrix composition and morphological features of the vertebral bodies and IVDs are likely contributors to the incidence and severity of spinal pathologies in T2D.This review will broadly examine the effects of AGEs on tissues in the spine in the context of T2D,with an emphasis on the changes in the vertebrae and the IVD.Along with the clinical and epidemiological findings,we will provide an overview of preclinical rodent models of T2D that exhibit deficits in the IVD and vertebral bone.Elucidating the role of AGEs and RAGE will be crucial for understanding the disease mechanisms and translation therapies of musculoskeletal pathologies in T2D.展开更多
AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for a...AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.展开更多
Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products(RAGE)axis activation in the development of ...Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products(RAGE)axis activation in the development of neoplasms,including gastric cancer(GC).This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu,not only by supporting phenotypic changes favoring growth and dissemination of tumor cells,but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection.In the present review,we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis.Finally,the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.展开更多
The inhibitory activity of lactic acid bacteria(LAB)toward advanced glycation end-products(AGEs)during vinegar fermentation was studied,and its relationships with the substrate consumption,antioxidant capacity,total p...The inhibitory activity of lactic acid bacteria(LAB)toward advanced glycation end-products(AGEs)during vinegar fermentation was studied,and its relationships with the substrate consumption,antioxidant capacity,total phenolic content,total flavonoid compounds,α-glucosidase,andα-amylase activity inhibition were evaluated.The vinegar was made from rice powder flour by liquid-state fermentation(LSF).The selected LAB strains were separately co-cultivated with Saccharomyces cerevisiae and Acetobacter pasteurianus 1.41 in alcoholic and acetic acid fermentation,respectively.Among 3 strains,Lactobacillus fermentum showed the strongest inhibitory effect on the formation of total fluorescent AGEs and carboxymethyl lysine(CML)/carboxyethyl lysine(CEL)in the fermentation process.The corresponding mechanisms included the acceleration of substrate consumtion,improvement of antioxidant activities,and inhibition ofα-glucosidase andα-amylase.In addition,the fluorescent AGEs and the CML/CEL were negatively correlated with the antioxidant activities,while theα-glucosidase andα-amylase activities were positively correlated with the total phenols and total flavonoids.Moreover,the variety of main flavor compounds increased,including esters,alcohols,phenols and acids.The results of the study support the potential use of screened LAB strains to inhibit the formation of fluorescent AGEs,CML and CEL on fermented products and in the food processing industry,without associated risks to consumers.展开更多
Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen,leading to the accumulation of advanced glycation end-products(AGEs)cross-links in collagenous tissues.More recently,A...Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen,leading to the accumulation of advanced glycation end-products(AGEs)cross-links in collagenous tissues.More recently,AGEs content has been related to loss of bone quality,independent of bone mass,and increased fracture risk with aging and diabetes.Loss of bone quality is mostly attributed to changes in material properties,structural organization,or cellular remodeling.Though all these factors play a role in bone fragility disease,some common recurring patterns can be found between diabetic and age-related bone fragility.The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation.This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales,collagen deformation mechanisms at the nanoscale,and resistance to bone fracture at the macroscale.展开更多
Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
The association between diabetes and hyperglycemia and the associated increased risk of several solid and hematologic malignancies has been the subject of investigation for many years.Although the association is not f...The association between diabetes and hyperglycemia and the associated increased risk of several solid and hematologic malignancies has been the subject of investigation for many years.Although the association is not fully understood,current knowledge clearly indicates that diabetes may influence malignant cell transformation by several mechanisms,including hyperinsulinemia,hyperglycemia and chronic inflammation.In this context,the receptor for advanced glycation end-products (RAGE) has emerged as a focal point in its contribution to malignant transformation and tumor growth.We high-light how RAGE,once activated,as it manifests itself in conditions such as diabetes or hyperglycemia,is able to continuously bring about an inflammatory milieu,thus supporting the contribution of chronic inflammation to the development of malignancies.展开更多
AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract ...AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferative effects of a control(unglycated bovine serum albumin),glucosederived AGEs(Glc-AGE),and glyceraldehyde-derived AGEs(Glycer-AGE),and the anti-proliferative effect of MK615 against AGEs,were evaluated using MTT assays.RESULTS:Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2.FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2.Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2.The growth indices for the control,Glc-AGE,and Glycer-AGE were 1.06 ± 0.08,0.99 ± 0.04,and 1.38 ± 0.05,respectively,in HuH7(P = 0.037),and were 1.03 ± 0.04,1.04 ± 0.03,and 1.07 ± 0.05,respectively,in HepG2(P > 0.05).When the cells were cultured simultaneously with Glycer-AGE and MK615,MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.CONCLUSION:Only Glycer-AGE has a proliferative effect on HuH7,which expresses a higher level of RAGE.MK615 suppresses the proliferative effect of GlycerAGE on HuH7 by decreasing the expression of RAGE.展开更多
AIM:To study the formation of intracellular glyceraldehyde-derived advanced glycation end products(Glycer-AGEs)in the presence of high concentrations of fructose.METHODS:Cells of the human hepatocyte cell line Hep3B w...AIM:To study the formation of intracellular glyceraldehyde-derived advanced glycation end products(Glycer-AGEs)in the presence of high concentrations of fructose.METHODS:Cells of the human hepatocyte cell line Hep3B were incubated with or without fructose for five days,and the corresponding cell lysates were separated by two-dimensional gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Glycer-AGEs were detected with the anti-Glycer-AGEs antibody.Furthermore,the identification of the proteins that are modified by glyceraldehyde in the presence of high concentrations of fructose was conducted using matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The protein and m RNA levels were determined by Western blotting and realtime reverse transcription PCR,respectively.RESULTS:The results of the two-dimensional gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated a greater amount of GlycerAGEs in the sample exposed to high concentrations of fructose than in the control.The detected GlycerAGEs showed isoelectric points in the range of 8.0-9.0and molecular weights in the range of 60-80 k Da.The heterogeneous nuclear ribonucleoprotein M(hn RNPM),which plays an important role in regulating gene expression by processing heterogeneous nuclear RNAs to form mature m RNAs,was identified as a modified protein using MALDI-TOF-MS.Increasing the concentration of fructose in the medium induced a concentration-dependent increase in the generated Glycer-AGEs.Furthermore,in an experiment using glyceraldehyde,which is a precursor of Glycer-AGEs,hn RNPM was found to be more easily glycated than the other proteins.CONCLUSION:The results suggest that glyceraldehyde-modified hn RNPM alters gene expression.This change may cause adverse effects in hepatocytes and may serve as a target for therapeutic intervention.展开更多
Objective:This study aimed to evaluate the influence of advanced glycation end-product(AGE)accumulation on the prevalence and severity of overactive bladder(OAB)in community-dwelling elderly adults.Methods:We conducte...Objective:This study aimed to evaluate the influence of advanced glycation end-product(AGE)accumulation on the prevalence and severity of overactive bladder(OAB)in community-dwelling elderly adults.Methods:We conducted a cross-sectional study involving 269 Japanese community dwellers aged≥75 years in 2015.AGE accumulation was non-invasively measured via skin autofluorescence(SAF)values using AGE Reader.The primary and secondary outcomes were the presence and severity of OAB evaluated using the Overactive Bladder Symptom Score(OABSS).Individuals with an urgency score of≥2 and sum score of≥3 were considered to have OAB.The associations of SAF with the prevalence and severity of OAB were assessed using logistic and linear regression models,respectively,adjusted for clinically important confounders.Results:The median age of participants was 78 years.Of 269 participants,110(40.9%)were men and 75(27.9%)had OAB.The median SAF was 2.2 arbitrary units(AUs).Increasing median SAF was observed with increasing age.Multivariable analysis revealed that SAF was not associated with either the likelihood of having OAB(odds ratio per AU=0.77,95%confidence interval:0.37-1.62)or the natural log-transformed OABSS(0 per AU=-0.07,95%confidence interval:-0.26-0.12).Conclusions:In this study,AGE accumulation,as assessed by SAF,was not associated with the prevalence and severity of OAB in Japanese community-dwelling elderly people aged≥75 years.展开更多
Advanced glycation endproducts (AGEs) is implicated in the pathogenesis of diabetic complications. Inhibiting the formation of AGEs and interfering with AGEs-mediated inflammation are two practicable strategies for de...Advanced glycation endproducts (AGEs) is implicated in the pathogenesis of diabetic complications. Inhibiting the formation of AGEs and interfering with AGEs-mediated inflammation are two practicable strategies for developing a dietary adjuvant against diabetic complications. This study evaluated the protective capacities against diabetic complications of several spices based on their inhibition of the formation of AGEs in an in vitro BSA/glucose system and on the AGEs-induced production of proinflammatory cytokine in RAW 264.7 macrophages. Among the tested spices, cinnamon exhibited most strongly inhibited both the formation of AGEs and the AGEs-induced production of nitric oxide, interleukin-6 and tumor necrosis factor-α. Additionally, correlative results revealed that the capacity of spices to inhibit the formation of AGEs is attributable to phenolic compounds and, in contrast, the capacity to inhibit AGEs-induced inflammation is attributable to condensed tannin. This investigation demonstrates the potential of cinnamon to serve as a dietary adjuvant against diabetic complications.展开更多
Advanced Glycation End Products (AGEs) have been associated as a possible <span>cause in inflammation-mediated chronic diseases such as diabetes, Alzhei</span>mer’s and cardiovascular disorders. Thus, inh...Advanced Glycation End Products (AGEs) have been associated as a possible <span>cause in inflammation-mediated chronic diseases such as diabetes, Alzhei</span>mer’s and cardiovascular disorders. Thus, inhibition of AGE formation repre<span>sents a prospective therapeutic target for the prevention and treatment of</span> these complications. This study investigated the individual and combined effect</span><span style="font-size:10.0pt;font-family:"">s</span><span style="font-size:10.0pt;font-family:""> of dietary ingredients, spices, on lowering AGEs formation in meat pat<span>ties. In the study, Carboxymethyllysine (CML), a well-investigated AGE is</span> used as a marker for AGEs and malondialdehyde (MDA) as an indicator for <span>lipid peroxidation. Nine spices were selected based on their ability to inhibit </span>the formation of AGEs at different stages of Maillard reactions. Individually, all the 9 selected spices significantly inhibited the formation of AGEs. Among <span>the 33 combinations of spices, 26 combinations significantly inhibited the</span> formation of AGEs. The highest reduction (84%) was found by the combination <span>of Black Pepper</span></span><span style="font-size:10.0pt;font-family:"">-</span><span style="font-size:10.0pt;font-family:"">Rose</span><span style="font-size:10.0pt;font-family:"">-</span><span style="font-size:10.0pt;font-family:"">Cumin. The individual spices failed to significantly </span><span style="font-size:10.0pt;font-family:"">lower the MDA </span><span style="font-size:10.0pt;font-family:"">concentration</span><span style="font-size:10.0pt;font-family:"">;however, all 33 combinations were able to signifi<span>cantly reduce MDA </span></span><span style="font-size:10.0pt;font-family:"">concentration</span><span style="font-size:10.0pt;font-family:"">. The results of this study showed that</span><span style="font-size:10.0pt;font-family:""> </span><span style="font-size:10.0pt;font-family:"">spices when supplemented in combinations are more effective in inhibiting <span>the formation of AGEs and in decreasing MDA </span></span><span style="font-size:10.0pt;font-family:"">concentration</span><span style="font-size:10.0pt;font-family:""> in meat patties.展开更多
Advanced Glycation End-Products (AGEs), play a crucial part in advancing the process of cellular skin aging and its link to chronological age was re-assessed. AGEs accumulation alters cell structure and function of mo...Advanced Glycation End-Products (AGEs), play a crucial part in advancing the process of cellular skin aging and its link to chronological age was re-assessed. AGEs accumulation alters cell structure and function of most types of skin cells, affecting skin’s mechanical and physiological properties, following the molecular transformations. Slowdown AGEs accumulation rate in skin, although a potent anti-aging strategy, is difficult and tricky. The lack of working methods for <span style="white-space:nowrap;"><i>In-Vitro</i></span> and <span style="white-space:nowrap;"><i>In-Vitro</i></span> measuring AGEs level complicates the evaluation and prediction of active ingredients’ ability to affect cellular AGEs accumulation. A two-step <span style="white-space:nowrap;"><i>In-Vitro</i></span> systematic screening method is proposed and three different cosmetic active ingredients were selected for its demonstration, using BSA-Glucose and Collagen-Glucose predicting models. Candidates’ effects on AGEs accumulation were evaluated as standalone, and when formulated in a blend. Additionally, the potency of non-invasive auto-fluorescence in-vivo measurement to detect AGEs levels among subjects of different ages was demonstrated. The results are presented in this work and the potential contribution of the proposed system to assist the desired inhibition of AGEs accumulation in skin is discussed.展开更多
基金This work was financially supported by The Jiangsu Provincial Maternal and Child Health Key Talents Project(F202042).
文摘The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.
文摘Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.
文摘Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms,including gallbladder cancer.In this regard,data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products(RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu,thus supporting tumor growth and development.AGEs are formed in biological systems or foods,and food-derived AGEs,also known as dietary AGEs are known to contribute to the systemic pool of AGEs.Once they bind to RAGE,the activation of multiple and crucial signaling pathways are triggered,thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration.In the present review,we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer,and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.
文摘BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(ε)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.
文摘Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products(RAGE)in orchestrating a plethora of proinflammatory cellular responses leading to many of the complications and end-organ damages reported in patients with diabetes mellitus(DM).During the coronavirus disease 2019(COVID-19)pandemic,many clinical reports have pointed out that DM increases the risk of COVID-19 complications,hospitalization requirements,as well as the overall severe acute respiratory syndrome coronavirus 2 case-fatality rate.In the present review,we intend to focus on how the basal activation state of the RAGE axis in common preexisting conditions in DM patients such as endothelial dysfunction and hyperglycemia-related prothrombotic phenotype,as well as the contribution of RAGE signaling in lung inflammation,may then lead to the increased mortality risk of COVID-19 in these patients.Additionally,the crosstalk between the RAGE axis with either another severe acute respiratory syndrome coronavirus 2 receptor molecule different of angiotensin-converting enzyme 2 or the renin-angiotensin system imbalance produced by viral infection,as well as the role of this multi-ligand receptor on the obesity-associated lowgrade inflammation in the higher risk for severe illness reported in diabetes patients with COVID-19,are also discussed.
基金the financial support received from the Natural Science Foundation of China(32202202 and 31871735)。
文摘Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods that covers the entire range of food categories,which limits the accurate risk assessment of dietary AGEs in human diseases.In this study,we first established an isotope dilution UHPLCQq Q-MS/MS-based method for simultaneous quantification of 10 major AGEs in foods.The contents of these AGEs were detected in 334 foods covering all main groups consumed in Western and Chinese populations.Nε-Carboxymethyllysine,methylglyoxal-derived hydroimidazolone isomers,and glyoxal-derived hydroimidazolone-1 are predominant AGEs found in most foodstuffs.Total amounts of AGEs were high in processed nuts,bakery products,and certain types of cereals and meats(>150 mg/kg),while low in dairy products,vegetables,fruits,and beverages(<40 mg/kg).Assessment of estimated daily intake implied that the contribution of food groups to daily AGE intake varied a lot under different eating patterns,and selection of high-AGE foods leads to up to a 2.7-fold higher intake of AGEs through daily meals.The presented AGE database allows accurate assessment of dietary exposure to these glycotoxins to explore their physiological impacts on human health.
基金This work is in part supported by NIH R01AR074441,K01AR069116,and P30 AR007992This investigation was supported by National Institutes of Health,National Research Service Award T32 DK108742,from the National Institute of Diabetes and Digestive and Kidney Diseases.
文摘Type 2 diabetes mellitus(T2D)is an increasingly prevalent disease with numerous comorbidities including many in the spine.T2D is strongly linked with vertebral fractures,intervertebral disc(IVD)degeneration,and severe chronic spinal pain.Yet the causative mechanism for these musculoskeletal impairments remains unclear.The chronic hyperglycemic state in T2D promotes the formation of advanced glycation end-products(AGEs)in tissues,and the accumulation of AGEs may play a role in musculoskeletal complications by modifying the extracellular matrix,impairing cellular homeostasis,and perpetuating an inflammatory cascade via its receptor(RAGE).The AGE and RAGE associated alterations in extracellular matrix composition and morphological features of the vertebral bodies and IVDs are likely contributors to the incidence and severity of spinal pathologies in T2D.This review will broadly examine the effects of AGEs on tissues in the spine in the context of T2D,with an emphasis on the changes in the vertebrae and the IVD.Along with the clinical and epidemiological findings,we will provide an overview of preclinical rodent models of T2D that exhibit deficits in the IVD and vertebral bone.Elucidating the role of AGEs and RAGE will be crucial for understanding the disease mechanisms and translation therapies of musculoskeletal pathologies in T2D.
基金Supported by the National Natural Science Foundation of China(No.82071888)the Natural Science Foundation of Shandong Province(No.ZR2021MH351,No.ZR2020MH074)+1 种基金the Introduction and Cultivation Project for Young Innovative Talents in Shandong ProvinceWeifang Science and Technology Development Plan(No.2021GX057).
文摘AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.
文摘Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products(RAGE)axis activation in the development of neoplasms,including gastric cancer(GC).This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu,not only by supporting phenotypic changes favoring growth and dissemination of tumor cells,but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection.In the present review,we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis.Finally,the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.
基金the National Natural Science Foundation of China(31601455)National Natural Science Foundation of China(32001705)the Science and Technology Innovation Project of Hubei Grain Bureau(2017/58)。
文摘The inhibitory activity of lactic acid bacteria(LAB)toward advanced glycation end-products(AGEs)during vinegar fermentation was studied,and its relationships with the substrate consumption,antioxidant capacity,total phenolic content,total flavonoid compounds,α-glucosidase,andα-amylase activity inhibition were evaluated.The vinegar was made from rice powder flour by liquid-state fermentation(LSF).The selected LAB strains were separately co-cultivated with Saccharomyces cerevisiae and Acetobacter pasteurianus 1.41 in alcoholic and acetic acid fermentation,respectively.Among 3 strains,Lactobacillus fermentum showed the strongest inhibitory effect on the formation of total fluorescent AGEs and carboxymethyl lysine(CML)/carboxyethyl lysine(CEL)in the fermentation process.The corresponding mechanisms included the acceleration of substrate consumtion,improvement of antioxidant activities,and inhibition ofα-glucosidase andα-amylase.In addition,the fluorescent AGEs and the CML/CEL were negatively correlated with the antioxidant activities,while theα-glucosidase andα-amylase activities were positively correlated with the total phenols and total flavonoids.Moreover,the variety of main flavor compounds increased,including esters,alcohols,phenols and acids.The results of the study support the potential use of screened LAB strains to inhibit the formation of fluorescent AGEs,CML and CEL on fermented products and in the food processing industry,without associated risks to consumers.
基金supported by the National Institutes of Health under Award Number 1R21AR077881.
文摘Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen,leading to the accumulation of advanced glycation end-products(AGEs)cross-links in collagenous tissues.More recently,AGEs content has been related to loss of bone quality,independent of bone mass,and increased fracture risk with aging and diabetes.Loss of bone quality is mostly attributed to changes in material properties,structural organization,or cellular remodeling.Though all these factors play a role in bone fragility disease,some common recurring patterns can be found between diabetic and age-related bone fragility.The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation.This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales,collagen deformation mechanisms at the nanoscale,and resistance to bone fracture at the macroscale.
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
文摘The association between diabetes and hyperglycemia and the associated increased risk of several solid and hematologic malignancies has been the subject of investigation for many years.Although the association is not fully understood,current knowledge clearly indicates that diabetes may influence malignant cell transformation by several mechanisms,including hyperinsulinemia,hyperglycemia and chronic inflammation.In this context,the receptor for advanced glycation end-products (RAGE) has emerged as a focal point in its contribution to malignant transformation and tumor growth.We high-light how RAGE,once activated,as it manifests itself in conditions such as diabetes or hyperglycemia,is able to continuously bring about an inflammatory milieu,thus supporting the contribution of chronic inflammation to the development of malignancies.
基金Supported by A Research Grant from the Biomarker Society
文摘AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferative effects of a control(unglycated bovine serum albumin),glucosederived AGEs(Glc-AGE),and glyceraldehyde-derived AGEs(Glycer-AGE),and the anti-proliferative effect of MK615 against AGEs,were evaluated using MTT assays.RESULTS:Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2.FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2.Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2.The growth indices for the control,Glc-AGE,and Glycer-AGE were 1.06 ± 0.08,0.99 ± 0.04,and 1.38 ± 0.05,respectively,in HuH7(P = 0.037),and were 1.03 ± 0.04,1.04 ± 0.03,and 1.07 ± 0.05,respectively,in HepG2(P > 0.05).When the cells were cultured simultaneously with Glycer-AGE and MK615,MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.CONCLUSION:Only Glycer-AGE has a proliferative effect on HuH7,which expresses a higher level of RAGE.MK615 suppresses the proliferative effect of GlycerAGE on HuH7 by decreasing the expression of RAGE.
基金Supported by Grants from the Japan Society for the Promotion of Science,No.22300264 and No.25282029
文摘AIM:To study the formation of intracellular glyceraldehyde-derived advanced glycation end products(Glycer-AGEs)in the presence of high concentrations of fructose.METHODS:Cells of the human hepatocyte cell line Hep3B were incubated with or without fructose for five days,and the corresponding cell lysates were separated by two-dimensional gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Glycer-AGEs were detected with the anti-Glycer-AGEs antibody.Furthermore,the identification of the proteins that are modified by glyceraldehyde in the presence of high concentrations of fructose was conducted using matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The protein and m RNA levels were determined by Western blotting and realtime reverse transcription PCR,respectively.RESULTS:The results of the two-dimensional gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated a greater amount of GlycerAGEs in the sample exposed to high concentrations of fructose than in the control.The detected GlycerAGEs showed isoelectric points in the range of 8.0-9.0and molecular weights in the range of 60-80 k Da.The heterogeneous nuclear ribonucleoprotein M(hn RNPM),which plays an important role in regulating gene expression by processing heterogeneous nuclear RNAs to form mature m RNAs,was identified as a modified protein using MALDI-TOF-MS.Increasing the concentration of fructose in the medium induced a concentration-dependent increase in the generated Glycer-AGEs.Furthermore,in an experiment using glyceraldehyde,which is a precursor of Glycer-AGEs,hn RNPM was found to be more easily glycated than the other proteins.CONCLUSION:The results suggest that glyceraldehyde-modified hn RNPM alters gene expression.This change may cause adverse effects in hepatocytes and may serve as a target for therapeutic intervention.
基金supported by a Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research(KAKENHI)[Grant No.JP18K09975].
文摘Objective:This study aimed to evaluate the influence of advanced glycation end-product(AGE)accumulation on the prevalence and severity of overactive bladder(OAB)in community-dwelling elderly adults.Methods:We conducted a cross-sectional study involving 269 Japanese community dwellers aged≥75 years in 2015.AGE accumulation was non-invasively measured via skin autofluorescence(SAF)values using AGE Reader.The primary and secondary outcomes were the presence and severity of OAB evaluated using the Overactive Bladder Symptom Score(OABSS).Individuals with an urgency score of≥2 and sum score of≥3 were considered to have OAB.The associations of SAF with the prevalence and severity of OAB were assessed using logistic and linear regression models,respectively,adjusted for clinically important confounders.Results:The median age of participants was 78 years.Of 269 participants,110(40.9%)were men and 75(27.9%)had OAB.The median SAF was 2.2 arbitrary units(AUs).Increasing median SAF was observed with increasing age.Multivariable analysis revealed that SAF was not associated with either the likelihood of having OAB(odds ratio per AU=0.77,95%confidence interval:0.37-1.62)or the natural log-transformed OABSS(0 per AU=-0.07,95%confidence interval:-0.26-0.12).Conclusions:In this study,AGE accumulation,as assessed by SAF,was not associated with the prevalence and severity of OAB in Japanese community-dwelling elderly people aged≥75 years.
文摘Advanced glycation endproducts (AGEs) is implicated in the pathogenesis of diabetic complications. Inhibiting the formation of AGEs and interfering with AGEs-mediated inflammation are two practicable strategies for developing a dietary adjuvant against diabetic complications. This study evaluated the protective capacities against diabetic complications of several spices based on their inhibition of the formation of AGEs in an in vitro BSA/glucose system and on the AGEs-induced production of proinflammatory cytokine in RAW 264.7 macrophages. Among the tested spices, cinnamon exhibited most strongly inhibited both the formation of AGEs and the AGEs-induced production of nitric oxide, interleukin-6 and tumor necrosis factor-α. Additionally, correlative results revealed that the capacity of spices to inhibit the formation of AGEs is attributable to phenolic compounds and, in contrast, the capacity to inhibit AGEs-induced inflammation is attributable to condensed tannin. This investigation demonstrates the potential of cinnamon to serve as a dietary adjuvant against diabetic complications.
文摘Advanced Glycation End Products (AGEs) have been associated as a possible <span>cause in inflammation-mediated chronic diseases such as diabetes, Alzhei</span>mer’s and cardiovascular disorders. Thus, inhibition of AGE formation repre<span>sents a prospective therapeutic target for the prevention and treatment of</span> these complications. This study investigated the individual and combined effect</span><span style="font-size:10.0pt;font-family:"">s</span><span style="font-size:10.0pt;font-family:""> of dietary ingredients, spices, on lowering AGEs formation in meat pat<span>ties. In the study, Carboxymethyllysine (CML), a well-investigated AGE is</span> used as a marker for AGEs and malondialdehyde (MDA) as an indicator for <span>lipid peroxidation. Nine spices were selected based on their ability to inhibit </span>the formation of AGEs at different stages of Maillard reactions. Individually, all the 9 selected spices significantly inhibited the formation of AGEs. Among <span>the 33 combinations of spices, 26 combinations significantly inhibited the</span> formation of AGEs. The highest reduction (84%) was found by the combination <span>of Black Pepper</span></span><span style="font-size:10.0pt;font-family:"">-</span><span style="font-size:10.0pt;font-family:"">Rose</span><span style="font-size:10.0pt;font-family:"">-</span><span style="font-size:10.0pt;font-family:"">Cumin. The individual spices failed to significantly </span><span style="font-size:10.0pt;font-family:"">lower the MDA </span><span style="font-size:10.0pt;font-family:"">concentration</span><span style="font-size:10.0pt;font-family:"">;however, all 33 combinations were able to signifi<span>cantly reduce MDA </span></span><span style="font-size:10.0pt;font-family:"">concentration</span><span style="font-size:10.0pt;font-family:"">. The results of this study showed that</span><span style="font-size:10.0pt;font-family:""> </span><span style="font-size:10.0pt;font-family:"">spices when supplemented in combinations are more effective in inhibiting <span>the formation of AGEs and in decreasing MDA </span></span><span style="font-size:10.0pt;font-family:"">concentration</span><span style="font-size:10.0pt;font-family:""> in meat patties.
文摘Advanced Glycation End-Products (AGEs), play a crucial part in advancing the process of cellular skin aging and its link to chronological age was re-assessed. AGEs accumulation alters cell structure and function of most types of skin cells, affecting skin’s mechanical and physiological properties, following the molecular transformations. Slowdown AGEs accumulation rate in skin, although a potent anti-aging strategy, is difficult and tricky. The lack of working methods for <span style="white-space:nowrap;"><i>In-Vitro</i></span> and <span style="white-space:nowrap;"><i>In-Vitro</i></span> measuring AGEs level complicates the evaluation and prediction of active ingredients’ ability to affect cellular AGEs accumulation. A two-step <span style="white-space:nowrap;"><i>In-Vitro</i></span> systematic screening method is proposed and three different cosmetic active ingredients were selected for its demonstration, using BSA-Glucose and Collagen-Glucose predicting models. Candidates’ effects on AGEs accumulation were evaluated as standalone, and when formulated in a blend. Additionally, the potency of non-invasive auto-fluorescence in-vivo measurement to detect AGEs levels among subjects of different ages was demonstrated. The results are presented in this work and the potential contribution of the proposed system to assist the desired inhibition of AGEs accumulation in skin is discussed.
