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

作者:Pan, Yong; Zhu, Guanghui; Wang, Yi; Cai, Lu; Cai, Yuepiao; Hu, Jie; Li, Yilan; Yan, Yongbo; Wang, Zengshou; Li, Xiaokun; Wei, Tiemin*; Liang, Guang
来源:Journal of Nutritional Biochemistry, 2013, 24(1): 146-155.
DOI:10.1016/j.jnutbio.2012.03.012

摘要

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 mu M 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 kappa B 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.