Abstract
Diabetic nephropathy (DN) is the most prevalent and fatal complication of diabetes. The progression of the DN is acceleated by both the formation and accumulation of advanced glycation end products (AGEs). Several synthetic compounds have been proposed to inhibit AGE formation; however, their use is associated with certain side effects. In this study, a natural compound derived from the brown seaweed Ecklonia cava was explored as a natural agent for the prevention and alleviation of DN. Specifically, the protective effect of phlorofucofuroeckol-A (PFFA) was investigated against methylglyoxal-derived AGE-induced apoptosis in mesangial cells. PFFA reduced methylglyoxal glycation and the accumulation of methylglyoxal-derived AGEs. Moreover, PFFA inhibited the interaction between the receptor for AGE (RAGE) and AGEs by forming stable ligands with RAGE. The mechanism underlying the prevention of apoptosis by PFFA was found to involve the inhibition of the phosphorylation of mitogen-activated kinase-related proteins, reversal of the downregulation of intracellular oxidative stress-associated proteins, and normalization of the levels of proteins regulating mitochondria-related intrinsic apoptosis. These findings highlight PFFAs as promising natural therapeutic agents for the prevention or alleviation of DN.
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