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 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.
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.).
Qilu
Q
Fang
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.).
Liancheng
L
Deng
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.).
Lintao
L
Wang
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.).
Yali
Y
Zhang
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.).
Qiaoyou
Q
Weng
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.).
Haimin
H
Yin
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.).
Yong
Y
Pan
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.).
Chao
C
Tong
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.).
Jingying
J
Wang
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.
Guang
G
Liang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C000603962:1-(3,4-dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047188:Chalcones; D016207:Cytokines; D004041:Dietary Fats; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019308:Palmitic Acid; D020928:Mitogen-Activated Protein Kinases