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Effect of rosmarinic acid on experimental diabetic nephropathy.

Abstract
Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Rosmarinic acid (RA) is a naturally occurring phenolic acid. This study was conducted to investigate the efficacy of RA on DN and to elucidate the potential mechanism. High glucose (HG)-stimulated cultured human renal proximal tubular epithelial cells (HK-2) analysed CTGF expression by western blotting, and it was investigated whether extracellular signal-regulated kinase (ERK) signalling pathway was involved. Using streptozotocin (STZ)-induced rat animal models, diabetic rats were randomized to receive intragastric (i.g.) doses of RA. Renal tissue, blood and urine samples were collected to determine biochemical index and analyse protein expression. In vitro study, RA reduced CTGF excretion in HG-induced HK-2 cells through the ERK signalling pathway. In an in vivo study, I.g. of RA 7.5 or 15 mg/kg significantly ameliorated renal function and increased body-weight. Meanwhile, RA reduced renal CTGF expression by immunohistochemical staining and reduced serum levels of CTGF. Besides, there were no significant differences in glycaemia levels between the RA groups compared with the STZ-treated group. Furthermore, RA ameliorated renal pathology. These results suggest that RA exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using RA in the treatment of DN.
AuthorsWang-Lin Jiang, Yong Xu, Shu-Ping Zhang, Jian Hou, Hai-Bo Zhu
JournalBasic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 110 Issue 4 Pg. 390-5 (Apr 2012) ISSN: 1742-7843 [Electronic] England
PMID22053730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.
Chemical References
  • Cinnamates
  • Depsides
  • Connective Tissue Growth Factor
  • Streptozocin
  • rosmarinic acid
Topics
  • Animals
  • Body Weight (drug effects)
  • Cells, Cultured
  • Cinnamates (administration & dosage, pharmacology)
  • Connective Tissue Growth Factor (metabolism)
  • Depsides (administration & dosage, pharmacology)
  • Diabetes Mellitus, Experimental (complications)
  • Diabetic Nephropathies (drug therapy, pathology)
  • Dose-Response Relationship, Drug
  • Epithelial Cells (drug effects, metabolism)
  • Humans
  • Kidney Tubules, Proximal (drug effects, metabolism)
  • Male
  • Pilot Projects
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin

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