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J Pharmacol Exp Ther. 2015 Nov;355(2):235-46. doi: 10.1124/jpet.115.226860. Epub 2015 Sep 9.

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.

Author information

1
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China (Q.F., L.D., L.W., Y.Z., Q.W., H.Y.,Y.P.,C.T., J.W., G.L.); Department of Pharmacy, Affiliated Sixth Hospital, Wenzhou Medical University, Lishui, Zhejiang, China (L.D.); and Diabetes Center and Department of Endocrinology, Affiliated Second Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China (H.Y.).
2
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China (Q.F., L.D., L.W., Y.Z., Q.W., H.Y.,Y.P.,C.T., J.W., G.L.); Department of Pharmacy, Affiliated Sixth Hospital, Wenzhou Medical University, Lishui, Zhejiang, China (L.D.); and Diabetes Center and Department of Endocrinology, Affiliated Second Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China (H.Y.) wzmcliangguang@163.com.

Abstract

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 has 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. 1-(3,4-Dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one (L2H17) is a chalcone that we have previously synthesized and found capable of inhibiting the lipopolysaccharide-induced inflammatory response in macrophages. In this study, we investigated L2H17's effect on obesity-induced renal injury using palmitic acid-induced mouse peritoneal macrophages and high fat diet-fed mice. Our results indicate that L2H17 protects against renal injury through the inhibition of the mitogen-activated protein kinase/nuclear factor κB pathways significantly by decreasing the expression of proinflammatory 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.

PMID:
26354992
DOI:
10.1124/jpet.115.226860
[Indexed for MEDLINE]

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