title: 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.
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.
authors: School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou, People's Republic of China.
authors: Yong
authors: Y
authors: Pan
authors: Guanghui
authors: G
authors: Zhu
authors: Yi
authors: Y
authors: Wang
authors: Lu
authors: L
authors: Cai
authors: Yuepiao
authors: Y
authors: Cai
authors: Jie
authors: J
authors: Hu
authors: Yilan
authors: Y
authors: Li
authors: Yongbo
authors: Y
authors: Yan
authors: Zengshou
authors: Z
authors: Wang
authors: Xiaokun
authors: X
authors: Li
authors: Tiemin
authors: T
authors: Wei
authors: Guang
authors: G
authors: Liang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001969:Bromobenzenes / Q000494:pharmacology*; D003474:Curcumin / Q000031:analogs & derivatives*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000009:adverse effects; D006321:Heart / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D010422:Pentanones / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C550703:1,5-bis(2-bromophenyl)penta-1,4-dien-3-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001969:Bromobenzenes; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D010422:Pentanones; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin; D005947:Glucose