scholarly journals 3′-O-β-d-glucopyranosyl-α,4,2′,4′,6′-pentahydroxy-dihydrochalcone, from Bark of Eysenhardtia polystachya Prevents Diabetic Nephropathy via Inhibiting Protein Glycation in STZ-Nicotinamide Induced Diabetic Mice

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1214 ◽  
Author(s):  
Rosa Pérez Gutierrez ◽  
Abraham García Campoy ◽  
Silvia Paredes Carrera ◽  
Alethia Muñiz Ramirez ◽  
José Mota Flores ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Advanced Glycation End Products ◽  
Renal Damage ◽  
Histological Analysis ◽  
Protein Glycation ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3′-O-β-d-glucopyranosyl α,4,2′,4′,6′-pentahydroxy–dihydrochalcone (1) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya. The aim was to investigate whether (1) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly (p < 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly (p < 0.05) attenuated by (1) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound (1) attenuated the renal damage in diabetic mice by inhibiting AGEs formation.

Flavonoids derived from buckwheat hull break advanced glycation end-products and improve diabetic nephropathy

2021 ◽  
Author(s):  
Tianzhu Li ◽  
Yuying Yang ◽  
Xiujuan Wang ◽  
Weichang Dai ◽  
Lan Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Advanced Glycation End Products ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Important Complication ◽  
Glycation End Products ◽  
End Products

Diabetic nephropathy (DN) is the most important complication of diabetic patients. The accumulation of advanced glycation end-products (AGEs) is the main reason for the development of DN. This study investigated...

Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy

2016 ◽  
Vol 7 (5-6) ◽  
pp. 293-309 ◽  
Author(s):  
Anil Kumar Pasupulati ◽  
P. Swathi Chitra ◽  
G. Bhanuprakash Reddy
Keyword(s):  
Diabetic Nephropathy ◽  
Advanced Glycation End Products ◽  
Basement Membranes ◽  
Renal Outcome ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Molecular Events ◽  
Glycation End Products ◽  
End Products

AbstractDiabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff’s base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed.

scholarly journals Advanced Glycation end Products, Oxidative Stress and Diabetic Nephropathy

2010 ◽  
Vol 3 (2) ◽  
pp. 101-108 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Advanced Glycation End Products ◽  
Stress Generation ◽  
Stress System ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Stage Renal Disease

About 246 million people worldwide had diabetes in 2007. The global figure of people with diabetes is projected to increase to 370 million in 2030. As the prevalence of diabetes has risen to epidemic proportions worldwide, diabetic nephropathy has become one of the most challenging health problems. Therapeutic options such as strict blood glucose and blood pressure controls are effective for preventing diabetic nephropathy, but are far from satisfactory, and the number of diabetic patients on end-stage renal disease is still increasing. Therefore, a novel therapeutic strategy that could halt the progression of diabetic nephropathy should be developed. There is accumulating evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate under diabetes, play a role in diabetic nephropathy via oxidative stress generation. In this paper, we review the pathophysiological role of AGEs and their receptor (RAGE)-oxidative stress system in diabetic nephropathy.

scholarly journals The Extract ofLitsea japonicaReduced the Development of Diabetic Nephropathy via the Inhibition of Advanced Glycation End Products Accumulation in db/db Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Eunjin Sohn ◽  
Junghyun Kim ◽  
Chan-Sik Kim ◽  
Yun Mi Lee ◽  
Kyuhyung Jo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Advanced Glycation End Products ◽  
Immunohistochemical Analysis ◽  
Diabetic Mice ◽  
Advanced Glycation ◽  
Morphological Alterations ◽  
Glycation End Products ◽  
Podocyte Loss ◽  
End Products

Increasing evidence indicates that advanced glycation end products (AGEs) contribute to the pathogenesis of diabetic nephropathy. The aim of this study was to investigate the protective effect ofL. japonicaextract (LJE) against renal damage in the db/db mouse. LJE (100 or 250 mg/kg per day) was given to diabetic mice for 12 weeks. Body weight, blood glucose levels, glycated hemoglobin (HbA1c) levels, and proteinuria were examined. Inin vitroassay of the inhibition of AGE formation, immunohistochemical analysis of podocyte loss and AGE accumulations were performed. In 20-week-old db/db mice, severe hyperglycemia developed, and proteinuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. LJE treatment significantly reduced proteinuria and AGE accumulations in diabetic mice. Moreover, the loss of nephrin, an important slit diaphragm component in the kidneys, was restored by LJE treatment. Our studies suggest that LJE might be beneficial for the treatment of diabetic nephropathy. The ability of LJE to attenuate proteinuria and podocyte dysfunction may be mediated by the inhibition of AGE accumulation in the context of diabetic nephropathy in db/db mice.

scholarly journals Advanced Glycation End Products and Oxidative Stress in a Hyperglycaemic Environment

2021 ◽  
Author(s):  
Akio Nakamura ◽  
Ritsuko Kawahrada
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Advanced Glycation End Products ◽  
Reactive Oxygen ◽  
Protein Glycation ◽  
Oxygen Species ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

Protein glycation is the random, nonenzymatic reaction of sugar and protein induced by diabetes and ageing; this process is quite different from glycosylation mediated by the enzymatic reactions catalysed by glycosyltransferases. Schiff bases form advanced glycation end products (AGEs) via intermediates, such as Amadori compounds. Although these AGEs form various molecular species, only a few of their structures have been determined. AGEs bind to different AGE receptors on the cell membrane and transmit signals to the cell. Signal transduction via the receptor of AGEs produces reactive oxygen species in cells, and oxidative stress is responsible for the onset of diabetic complications. This chapter introduces the molecular mechanisms of disease onset due to oxidative stress, including reactive oxygen species, caused by AGEs generated by protein glycation in a hyperglycaemic environment.

scholarly journals De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation End Products a Key Driver?

2021 ◽  
Vol 11 ◽  
Author(s):  
Ahmed Abdel-Razik ◽  
Walaa Shabana ◽  
Ahmed Mohamed El Nakib ◽  
Mostafa Abdelsalam ◽  
Ahmed Abdelwahab ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Hepatitis C ◽  
Advanced Glycation End Products ◽  
Cox Regression ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Cox Regression Analysis ◽  
Glycation End Products ◽  
End Products

Background and PurposeThe advanced glycation end products (AGEs) have been implicated in different diseases’ pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with hepatitis C-related cirrhosis.MethodsOnly 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period.ResultsHCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that body mass index (P=0.013), homeostatic model assessment-insulin resistance (P=0.006), alpha-fetoprotein (P &lt;0.001), and AGEs levels (P &lt;0.001) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that AFP and AGEs were the powerful parameters related to the HCC occurrence (all P&lt;0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P&lt;0.001), using the receiver operating characteristic curve, for prediction of HCC development.ConclusionThis work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.

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