BACKGROUND AND PURPOSEInflammation 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 APPROACHPrimary 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-a levels and expression of inflammatory genes in the kidney were assessed. KEY RESULTSPretreatment of MPMs with C66 reduced HG-stimulated production of TNF-a and NO, inhibited HG-induced IL-1b, TNF-a, 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-a 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 IMPLICATIONSThe anti-inflammatory effects of C66 are mediated by inhibiting HG-induced activation of the JNK/NF-kB 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.

Permanent adsorption-conversion of lithium polysulfides by iron single atom anchored porous nitrogen-rich carbon nanocages endows lithium sulfur batteries with long lasting rate performance.

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