Attenuation of high-glucose-induced inflammatory response by a novel curcumin derivative B06 contributes to its protection from diabetic pathogenic changes in rat kidney and heart

J Nutr Biochem. 2013 Jan;24(1):146-55. doi: 10.1016/j.jnutbio.2012.03.012. Epub 2012 Jul 21.

Abstract

There is increasing evidence indicating that inflammatory processes are involved in the development and progression of diabetic complications. However, effective anti-inflammatory treatments for patients who have diabetic complications have yet been practically identified. Curcumin is a main component of Curcuma longa with numerous pharmacological activities. Previously, we synthesized a novel curcumin analogue (B06) that exhibited an improved pharmacokinetic and enhanced anti-inflammatory activity compared to curcumin. The present study aimed to test the hypothesis that B06 may reduce high-glucose-induced inflammation and inflammation-mediated diabetic complications. In vitro, pretreatment with B06 at a concentration of 5 μM significantly reduced the high-glucose-induced overexpression of inflammatory cytokines in macrophages. This anti-inflammatory activity of B06 is associated with its inhibition of c-Jun N-terminal kinase/nuclear factor κB activation. In vivo, despite that B06 administration at 0.2 mg · kg(-1) · d(-1) for 6 weeks did not affect the blood glucose profile of diabetic rats, the B06-treated animals displayed significant decreases in inflammatory mediators in the serum, kidney, and heart and renal macrophage infiltration. This was accompanied with an attenuation of diabetes-induced structural and functional abnormalities in the kidney and heart. Taken together, these data suggest that the novel derivative B06 might be a potential therapeutic agent for diabetic complications via an anti-inflammatory mechanism and support the potential application in diabetic complication therapy via anti-inflammatory strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Bromobenzenes / pharmacology*
  • Curcumin / analogs & derivatives*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetic Nephropathies / prevention & control
  • Dose-Response Relationship, Drug
  • Glucose / adverse effects
  • Heart / drug effects*
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / pharmacology
  • Interleukin-6 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Kidney / drug effects*
  • Kidney / pathology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myocardium / pathology*
  • NF-kappa B / metabolism
  • Pentanones / pharmacology*
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 1,5-bis(2-bromophenyl)penta-1,4-dien-3-one
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bromobenzenes
  • Inflammation Mediators
  • Interleukin-6
  • NF-kappa B
  • Pentanones
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases
  • Curcumin
  • Glucose