Diabetic nephropathy (DN) is a major complication in long-standing diabetic patients, and effective therapies are required. In this study, we examined the effects and mechanisms of an arabinoglucan (AG) isolated from Angelica sinensis on DN, which was induced in rats by streptozotocin. The rats were intraperitoneally treated with AG for 8 weeks. Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen and proteinuria, along with marked enhanced mesangial expansion. All of these abnormalities were reversed by the AG. Overproliferation of glomerular mesangial cells (GMCs) was halted by AG treatment, and inflammation mediators were attenuated. Furthermore, the AG significantly inhibited the expression of nuclear factor-κB (NF-κB) and receptor for advanced glycation end products (RAGE), both in diabetic kidneys and in high glucose-induced GMCs. Using an NF-κB inhibitor, RAGE siRNA and RAGE-overexpressing plasmid, we further demonstrated that the AG inhibited GMC viability mediated by RAGE/NF-κB signaling pathway. More importantly, we show that the AG can directly interact with RAGE and disrupt RAGE binding to advanced glycation end products using microscale thermophoresis. These findings suggest that this AG, acting as a RAGE antagonist, is a promising agent for the prevention and treatment of DN.
Keywords: NF-κB; advanced glycation end product; diabetic nephropathy; glomerular mesangial cell; polysaccharide.
© 2019 John Wiley & Sons, Ltd.