Curcumolide reduces diabetic retinal vascular leukostasis and leakage partly via inhibition of the p38MAPK/NF-κ B signaling.

Abstract

Retinal inflammation in a hyperglycemic condition is believed to play a crucial role in the development of diabetic retinopathy, and targeting inflammatory mediators is a promising strategy for the control of diabetic retinopathy. Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. In this study, we demonstrate that treatment with curcumolide alleviated retinal inflammatory activities both in vitro and in vivo in a STZ-induced diabetic rat model and in TNF-α-stimulated HUVECs. Curcumolide alleviated retinal vascular permeability and leukostasis and attenuated the overexpression of TNF-α and ICAM-1 in diabetic retinas. Moreover, curcumolide also inhibited inducible p38 MAPK and NF-κB activation and the subsequent induction of proinflammatory mediators. These data suggest potential treatment strategies against diabetic retinopathy, particularly in the early stages of the disease.

• Authors: Yuan Cai, Wencan Li, Hongfeng Tu, Nanmei Chen, Zhipeng Zhong, Pengcheng Yan, Jianyong Dong
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 27 Issue 8 Pg. 1835-1839 (04 15 2017) ISSN: 1464-3405 [Electronic] England
• PMID: 28274631 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• NF-kappa B
• Sesquiterpenes
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, isolation & purification, therapeutic use)
• Curcuma (chemistry)
• Diabetes Mellitus, Experimental (complications, drug therapy, immunology)
• Diabetic Retinopathy (complications, drug therapy, immunology)
• Human Umbilical Vein Endothelial Cells
• Leukostasis (complications, drug therapy, immunology)
• Male
• NF-kappa B (antagonists & inhibitors, immunology)
• Rats
• Rats, Wistar
• Sesquiterpenes (chemistry, isolation & purification, therapeutic use)
• Signal Transduction (drug effects)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, immunology)