Inhibitory effects of the EtOH extract of Aster koraiensis on AGEs formation in STZ-induced diabetic rats and AGEs-induced protein cross-linking in vitro

Advanced glycation end products (AGEs) such as N^ε-(carboxy-methyl)lysine (CML) have been implicated in the development of diabetic nephropathy. The aim of this study was to investigate the inhibitory effects of ethanolic extract of Aster koraiensis (AKE) on AGEs formation and AGEs-collagen cross-linking in vitro and CMLs formation in streptozotocin (STZ)- induced diabetic rats. AKE significantly inhibited AGEs formation (IC₅₀ value of 18.74 µg/mL) and AGEs-collagen cross-linking (IC₅₀ value of 0.274 mg/mL) in vitro than the well-known glycation inhibitor aminoguanidine (IC₅₀ value of 72.12 µg/mL and 1.99 mg/mL, respectively). AKE (100 mg/kg per day) was given to diabetic rats for 9 weeks. In STZ-induced diabetic rats, severe hyperglycemia was developed, and urinary CMLs and plasma CMLs were markedly increased. Immunohistochemical stain revealed that CMLs were accumulated within renal glomerulus in STZ-induced diabetic rats. However, AKE significantly reduced urinary CMLs and plasma CMLs in diabetic rats. CMLs accumulation was inhibited by AKE treatment in the renal glomerulus. These results suggest that AKE had an inhibitory effect of AGE accumulation in the glomeruli of diabetic rat and could be an inhibitor of AGE-induced protein cross-linking. The oral administration of AKE may significantly help to prevent the progression of diabetic nephropathy in patients with diabetes.