Inhibition of Mitogen-Activated Protein Kinases/Nuclear Factor κB–Dependent Inflammation by a Novel Chalcone Protects the Kidney from High Fat Diet–Induced Injuries in Mice

The prevalence of obesity has increased dramatically worldwide, leading to increases in obesity-related complications, such as obesity-related glomerulopathy (ORG). Obesity is a state of chronic, low-grade inflammation, and increased inflammation in the adipose and kidney tissues have been shown to promote the progression of renal damage in obesity. Current therapeutic options for ORG are fairly limited, and as a result, we are seeing increased rates of progression to end-stage renal disease. Chalcones are a class of naturally occurring compounds with various pharmacological properties. L2H17 is a chalcone that we've previously synthesized and found capable of inhibiting LPS-induced inflammatory response in macrophages. In this study, we investigated L2H17's effect on obesity-induced renal injury, using palmitic acid (PA)-induced mouse peritoneal macrophages and high fat diet (HFD)-fed mice. Our results indicate that L2H17 protects against renal injury through the inhibition of the MAPK/NF-κB pathways, significantly decreasing the expression of pro-inflammatory cytokines and cell adhesion molecules and improving kidney histology and pathology. These findings lead us to believe that L2H17, as an anti-inflammatory agent, can be a potential therapeutic option in treating ORG.