Inhibition of high glucose-induced inflammatory response and macrophage infiltration by a novel curcumin derivative prevents renal injury in diabetic rats

Br J Pharmacol. 2012 Jun;166(3):1169-82. doi: 10.1111/j.1476-5381.2012.01854.x.


Background and purpose: Inflammation is involved in the development and/or progression of many diseases including diabetic complications. Investigations on novel anti-inflammatory agents may offer new approaches for the prevention of diabetic nephropathy. Our previous bioscreening of synthetic analogues of curcumin revealed C66 as a novel anti-inflammatory compound against LPS challenge in macrophages. In this study, we hypothesized that C66 affects high glucose (HG)-induced inflammation profiles in vitro and in vivo and then prevents renal injury in diabetic rats via its anti-inflammatory actions.

Experimental approach: Primary peritoneal macrophages (MPM), prepared from C57BL/6 mice, were treated with HG in the presence or absence of C66. Diabetes was induced in Sprague-Dawley rats with streptozotocin, and the effects of C66 (0.2, 1.0 or 5.0 mg·kg(-1) ), administered daily for 6 weeks, on plasma TNF-α levels and expression of inflammatory genes in the kidney were assessed.

Key results: Pretreatment of MPMs with C66 reduced HG-stimulated production of TNF-α and NO, inhibited HG-induced IL-1β, TNF-α, IL-6, IL-12, COX-2 and iNOS mRNA transcription, and the activation of JNK/NF-kB signalling. In vivo, C66 inhibited the increased plasma TNF-α levels and renal inflammatory gene expression, improved histological abnormalities and fibrosis of diabetic kidney, but did not affect the hyperglycaemia in these diabetic rats.

Conclusions and implications: The anti-inflammatory effects of C66 are mediated by inhibiting HG-induced activation of the JNK/NF-κB pathway, rather than by reducing blood glucose in diabetic rats. This novel compound is a potential anti-inflammatory agent and might be beneficial for the prevention of diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Benzylidene Compounds / administration & dosage
  • Benzylidene Compounds / chemistry
  • Benzylidene Compounds / pharmacology
  • Benzylidene Compounds / therapeutic use*
  • Blood Glucose / analysis
  • Blotting, Western
  • Body Weight / drug effects
  • Cell Culture Techniques
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Curcumin / administration & dosage
  • Curcumin / analogs & derivatives
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Cyclohexanones / administration & dosage
  • Cyclohexanones / chemistry
  • Cyclohexanones / pharmacology
  • Cyclohexanones / therapeutic use*
  • Cytokines / blood
  • Cytokines / immunology
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / immunology
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Dose-Response Relationship, Drug
  • Fibrosis
  • Glucose / administration & dosage*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Size / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction


  • 2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzylidene Compounds
  • Blood Glucose
  • Cyclohexanones
  • Cytokines
  • Curcumin
  • Glucose