A novel salviadione derivative, compound 15a, attenuates diabetes-induced renal injury by inhibiting NF-κB-mediated inflammatory responses.

Abstract

Diabetic nephropathy is the leading cause of renal failure worldwide. Elevated inflammatory signaling has been shown to lead to deterioration of renal function in human and experimental diabetes. We recently developed a salviadione derivative (compound 15a) that prevented microbial lipopolysaccharide-induced inflammatory responses, which are largely driven by nuclear factor-κB (NF-κB). In the present study, we have tested the hypothesis that 15a will protect kidneys from diabetes-induced dysfunction by suppressing NF-κB activation and inflammatory signaling. Treatment of diabetic mice with 15a inhibited diabetes-induced renal fibrosis, NF-κB activation, and upregulation of proinflammatory cytokines. Histologically, kidney specimens from diabetic mice treated with 15a were indistinguishable from non-diabetic controls. We confirmed our findings in cultured renal tubular epithelial cells exposed to high levels of glucose. In these cultured cells, 15a pretreatment prevented high glucose-induced NF-κB activation and expression of inflammatory cytokines. These protective effects were also reflected in reduced levels of proteins involved in matrix expansion. Overall, our studies show that a salviadione derivative, 15a, is effective in suppressing diabetes-induced NF-κB activation and inflammatory signaling.

• Authors: Li Li, Chunyong Ding, Chunpeng Zou, Zhi Xiong, Weiwei Zhu, Jianchang Qian, Mingjiang Xu, Ao Zhang, Guang Liang
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 409 Pg. 115322 (12 15 2020) ISSN: 1096-0333 [Electronic] United States
• PMID: 33171189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• NF-kappa B
• Glucose

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Cytokines (metabolism)
• Diabetes Mellitus, Experimental (complications, metabolism)
• Diabetic Nephropathies (drug therapy, metabolism)
• Epithelial Cells (drug effects, metabolism)
• Fibrosis (drug therapy, metabolism)
• Glucose (metabolism)
• Inflammation (drug therapy, metabolism)
• Kidney Tubules (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Rats
• Signal Transduction (drug effects)