title: Loganin attenuates diabetic nephropathy in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of advanced glycation end products.
abstract: OBJECTIVE
  Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of loganin on diabetic nephropathy in vivo.
  
  
  METHODS
  We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined.
  
  
  RESULTS
  The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney.
  
  
  CONCLUSIONS
  Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy.
authors.affiliation: National Standard Laboratory of Pharmacology for Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: National Standard Laboratory of Pharmacology for Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: landarykailau@126.com.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Gaohong
authors.initials: G
authors.lastname: Lv
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Jiangsu Engineering Research Center for Efficient Delivery System of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Maxwell Kim Kit
authors.initials: MK
authors.lastname: Lee
authors.affiliation: National Standard Laboratory of Pharmacology for Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Lu
authors.affiliation: National Standard Laboratory of Pharmacology for Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
authors.affiliation: National Standard Laboratory of Pharmacology for Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yunhao
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000009:adverse effects* / Q000097:blood; D039823:Iridoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology / Q000648:ultrastructure; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D018384:Oxidative Stress / Q000502:physiology; D010179:Pancreas / Q000503:physiopathology; D011507:Proteinuria / Q000188:drug therapy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D017931:DNA Primers; D017127:Glycation End Products, Advanced; D039823:Iridoids; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C059516:loganin
keywords: Advanced glycation end-products; Diabetes mellitus; Diabetic nephropathy; Kidney; Loganin