Scutellarin alleviates blood-retina-barrier oxidative stress injury initiated by activated microglia cells during the development of diabetic retinopathy

doi:10.1016/j.bcp.2018.11.011

	Scutellarin alleviates blood-retina-barrier oxidative stress injury initiated by activated microglia cells during the development of diabetic retinopathy
	Mei, Xiyu; Zhang, Tianyu; Ouyang, Hao; Lu, Bin; Wang, Zhengtao; Ji, Lili
刊名	Biochemical pharmacology
	2018-11-14
卷号	159 页码:82-95
ISSN号	1873-2968
DOI	10.1016/j.bcp.2018.11.011
文献子类	Article
英文摘要	The breakdown of blood-retinal barrier (BRB) is an early and typical event during the development of diabetic retinopathy (DR). Scutellarin (SC) is a natural flavonoid. This study aims to investigate the protection of SC from BRB damage via focusing on inhibiting microglia-initiated inflammation and subsequent oxidative stress injury. SC attenuated BRB breakdown and the reduced expression of claudin-1 and claudin-19 in STZ-induced diabetic mice. SC reduced microglia cells activation both in vivo and in vitro. The results of transendothelial/transepithelial electrical resistance (TEER/TER) and fluorescein isothiocyanate (FITC)-conjugated dextran cell permeability assay showed that SC attenuated BRB damage induced by d-glucose (25 mM)-stimulated microglia BV2 cells. SC suppressed nuclear factor κB (NFκB) activation and tumor necrosis factor (TNF)-α expression induced by d-glucose (25 mM) in BV2 cells. SC decreased the phosphorylation of extracellular regulated protein kinase (ERK)1/2 both in vivo and in vitro. MEK1/2 inhibitor U0126 reduced the d-glucose-induced NFκB nuclear accumulation and TNFα expression in BV2 cells. Next, SC improved the decreased expression of claudin-1 and claudin-19, the increased BRB damage and cellular reactive oxygen species (ROS) formation, and enhanced nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in TNFα-treated human retinal endothelial cells (HRECs) and APRE19 cells. Moreover, the SC-provided alleviation on BRB breakdown in STZ-induced diabetic mice was diminished in Nrf2 knock-out mice. In conclusion, SC alleviates BRB breakdown via abrogating retinal inflammatory responses and subsequent oxidative stress injury initiated by microglia cells that is activated by hyperglycemia during DR development.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266556]
专题	中国科学院上海药物研究所
通讯作者	Ji, Lili
作者单位	The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
推荐引用方式 GB/T 7714	Mei, Xiyu,Zhang, Tianyu,Ouyang, Hao,et al. Scutellarin alleviates blood-retina-barrier oxidative stress injury initiated by activated microglia cells during the development of diabetic retinopathy[J]. Biochemical pharmacology,2018,159:82-95.
APA	Mei, Xiyu,Zhang, Tianyu,Ouyang, Hao,Lu, Bin,Wang, Zhengtao,&Ji, Lili.(2018).Scutellarin alleviates blood-retina-barrier oxidative stress injury initiated by activated microglia cells during the development of diabetic retinopathy.Biochemical pharmacology,159,82-95.
MLA	Mei, Xiyu,et al."Scutellarin alleviates blood-retina-barrier oxidative stress injury initiated by activated microglia cells during the development of diabetic retinopathy".Biochemical pharmacology 159(2018):82-95.