title: Inhibition of high glucose-induced inflammatory response and macrophage infiltration by a novel curcumin derivative prevents renal injury in diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Bioorganic and Medicinal Chemistry Research Center, School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Yuepiao
authors.initials: Y
authors.lastname: Cai
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Congcong
authors.initials: C
authors.lastname: Yu
authors.forename: Jianling
authors.initials: J
authors.lastname: Li
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Feng
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001597:Benzylidene Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D003512:Cyclohexanones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D005947:Glucose / Q000008:administration & dosage*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C575443:2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001597:Benzylidene Compounds; D001786:Blood Glucose; D003512:Cyclohexanones; D016207:Cytokines; D003474:Curcumin; D005947:Glucose