Inhibition of high glucose-induced inflammation and fibrosis by a novel curcumin derivative prevents renal and heart injury in diabetic mice.

Abstract

Hyperglycemia-induced inflammation and fibrosis have important roles in the pathogenesis of diabetic nephropathy and cardiomyopathy. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be an effective approach to new avenue for treating diabetic complications. J17, a molecule with structural similarities to curcumin, exhibited good anti-inflammatory activities by inhibiting LPS-induced inflammatory response in macrophages. However, its ability to alleviate hyperglycemia-induced injury via its anti-inflammatory actions remained unclear. Thus, we reported that J17 exerts significant inhibitory effects on hyperglycemia-induced inflammation and fibrosis in NRK-52E cells, H9C2 cells and a streptozotocin-induced diabetic mouse model. We also found that the anti-inflammatory and anti-fibrosis activities of J17 are associated with the inhibition of the P38 and AKT signal pathway, respectively. In vivo oral administration of J17 suppressed hyperglycemia-induced inflammation, hypertrophy and fibrosis, thereby reducing key markers for renal and cardiac dysfunction and improving in fibrosis and pathological changes in both renal and cardiac tissues of diabetic mice. The results of this study indicated that J17 can be potentially used as a cardio- and reno-protective agent and that targeting the P38 and AKT pathways may be an effective therapeutic strategy for diabetic complications.

• Authors: Hongjin Chen, Xi Yang, Kongqin Lu, Chun Lu, Yunjie Zhao, Suqing Zheng, Jieli Li, Zhangjian Huang, Yi Huang, Yali Zhang, Guang Liang
• Journal: Toxicology letters (Toxicol Lett) Vol. 278 Pg. 48-58 (Aug 15 2017) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 28700904 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Blood Glucose
• Cytokines
• Inflammation Mediators
• Streptozocin
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• Curcumin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Blood Glucose (metabolism)
• Cell Line
• Curcumin (analogs & derivatives, pharmacology)
• Cytokines (metabolism)
• Diabetes Mellitus, Experimental (chemically induced, drug therapy, metabolism, pathology)
• Diabetic Cardiomyopathies (chemically induced, metabolism, pathology, prevention & control)
• Diabetic Nephropathies (chemically induced, metabolism, pathology, prevention & control)
• Fibrosis
• Inflammation Mediators (metabolism)
• Kidney (drug effects, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Streptozocin
• Time Factors
• p38 Mitogen-Activated Protein Kinases (metabolism)