Advanced glycation end-products(AGEs)are complex and heterogeneous compounds generated through various steps and are naturally produced during the glycation reaction.Excessively generated AGEs bind to long-lived prote...Advanced glycation end-products(AGEs)are complex and heterogeneous compounds generated through various steps and are naturally produced during the glycation reaction.Excessively generated AGEs bind to long-lived proteins such as collagen and cause renal dysfunction,leading to AGE-related diabetic nephropathy(DN).In this study,we aimed to confirm the therapeutic potential of marine biological resources by evaluating the role of diphlorethohydroxycarmalol(DPHC),a major phlorotannin compound contained in edible brown algae Ishige okamurae,in the key mechanisms involved in the pathogenesis and progression of AGE-induced DN.The AGE formation inhibitory and AGE-collagen cross-link inhibiting/breaking ability assay were performed to evaluate the anti-glycation effect of DPHC.The AGE-RAGE interaction inhibitory effect was evaluated through molecular docking study.The renoprotective effect of DPHC was confirmed in mouse glomerular mesangial cells.DPHC treatment exhibited anti-glycation ability through suppression of AGE formation and AGE-collagen cross-linking generation,and disruption of cross-links formed between AGE-collagen.In addition,DPHC pre-treatment significantly suppressed reactive oxygen species(ROS)production,intracellular methylglyoxal(MGO)/AGEs accumulation,and activation of apoptosis cascade by MGO.Moreover,DPHC suppressed AGE-receptor for AGE(RAGE)interaction by competing with MG-H1 for the binding site of RAGE.Furthermore,DPHC pre-treatment regulated apoptosis-related protein expression and increased Nrf2,Glo-1,HO-1,CAT,NQO1,and SOD1.These findings prove that the chemical structural characteristics of DPHC have the potential to prevent or manage AGE-induced DN by effectively mediating the key mechanisms responsible for its pathogenesis.展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(Ministry of Sci-ence and ICT,MSIT)(No.NRF-2020R1A2C2012608)supported by Korea Institute of Marine Science&Technology Promotion(KIMST)funded by the Ministry of Oceans and Fisheries(20220128).
文摘Advanced glycation end-products(AGEs)are complex and heterogeneous compounds generated through various steps and are naturally produced during the glycation reaction.Excessively generated AGEs bind to long-lived proteins such as collagen and cause renal dysfunction,leading to AGE-related diabetic nephropathy(DN).In this study,we aimed to confirm the therapeutic potential of marine biological resources by evaluating the role of diphlorethohydroxycarmalol(DPHC),a major phlorotannin compound contained in edible brown algae Ishige okamurae,in the key mechanisms involved in the pathogenesis and progression of AGE-induced DN.The AGE formation inhibitory and AGE-collagen cross-link inhibiting/breaking ability assay were performed to evaluate the anti-glycation effect of DPHC.The AGE-RAGE interaction inhibitory effect was evaluated through molecular docking study.The renoprotective effect of DPHC was confirmed in mouse glomerular mesangial cells.DPHC treatment exhibited anti-glycation ability through suppression of AGE formation and AGE-collagen cross-linking generation,and disruption of cross-links formed between AGE-collagen.In addition,DPHC pre-treatment significantly suppressed reactive oxygen species(ROS)production,intracellular methylglyoxal(MGO)/AGEs accumulation,and activation of apoptosis cascade by MGO.Moreover,DPHC suppressed AGE-receptor for AGE(RAGE)interaction by competing with MG-H1 for the binding site of RAGE.Furthermore,DPHC pre-treatment regulated apoptosis-related protein expression and increased Nrf2,Glo-1,HO-1,CAT,NQO1,and SOD1.These findings prove that the chemical structural characteristics of DPHC have the potential to prevent or manage AGE-induced DN by effectively mediating the key mechanisms responsible for its pathogenesis.
