title: XLF-III-43, a novel coumarin-aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products.
abstract: 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.
authors.affiliation: 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
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zheng
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hongqi
authors.initials: H
authors.lastname: Xin
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
mesh_terms: 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
chemical_list: D003374:Coumarins; D017127:Glycation End Products, Advanced; D012459:Salicylates; C548351:XLF-III-43