XLF-III-43, a novel coumarin-aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products.
Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications. The purpose of this study was to examine the novel coumarin-aspirin compound XLF-III-43 in the inhibition of AGE formation in diabetic nephropathy. In vitro analysis showed XLF-III-43 in a dose-dependent manner decreased glucose induced formation of glycation adducts on albumin and inhibited AGE-lysozyme crosslinking. The streptozotocin-induced diabetic rats were used to investigate the beneficial effects of XLF-III-43 treatment on diabetic nephropathy. Administration of XLF-III-43 significantly decreased (P<0.05) blood urea nitrogen and urinary albumin excretion. Moreover, XLF-III-43 ameliorated kidney hypertrophy, mesangial expansion and glomerulosclerosis in diabetic rats relative to untreated model group. These data correlated with decreased both AGE and downstream markers of AGE stress (TGF-beta1, CTGF, fibronectin and collagen IV fibrolysis) in kidneys of diabetic rats. These data support further development of XLF-III-43 for prevention of nephropathy via inhibition of AGE formation consequent to chronic hyperglycemia.
Li
Hongyan
H
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China. lhy2116@gmail.com
Zheng
Xuguang
X
Wang
Hongbo
H
Zhang
Yi
Y
Xin
Hongqi
H
Chen
Xiaoguang
X
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology* / Q000627:therapeutic use
D003374:Coumarins; D017127:Glycation End Products, Advanced; D012459:Salicylates; C548351:XLF-III-43