Abstract
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.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call