title: 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.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Wencan
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Tu
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Nanmei
authors.initials: N
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People's Republic of China. Electronic address: jianyd@wmu.edu.cn.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Dong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use*; D030024:Curcuma / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells; D018921:Leukostasis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D012717:Sesquiterpenes; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Curcumolide; Diabetic retinopathy; NF-κ B signaling; Retinal vascular leakage; Retinal vascular leukostasis; p38MAPK signaling