|Author||Fang, Qilu ♦ Zhao, Leping ♦ Wang, Yi ♦ Zhang, Yali ♦ Li, Zhaoyu ♦ Pan, Yong ♦ Kanchana, Karvannan ♦ Wang, Jingying ♦ Tong, Chao ♦ Li, Dan ♦ Liang, Guang|
|Source||United States Department of Energy Office of Scientific and Technical Information|
|Subject Keyword||APPLIED LIFE SCIENCES ♦ ANTIPYRETICS ♦ CREATININE ♦ FIBROSIS ♦ GLUCOSE ♦ INFLAMMATION ♦ INJURIES ♦ KIDNEYS ♦ LYMPHOKINES ♦ MACROPHAGES ♦ MICE ♦ ORAL ADMINISTRATION ♦ THERAPY|
|Abstract||Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.|
|Learning Resource Type||Article|
|Publisher Place||United States|
|Journal||Toxicology and Applied Pharmacology|
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