Natural flavonoid galangin alleviates microglia-trigged blood-retinal barrier dysfunction during the development of diabetic retinopathy

doi:10.1016/j.jnutbio.2018.11.006

	Natural flavonoid galangin alleviates microglia-trigged blood-retinal barrier dysfunction during the development of diabetic retinopathy
	Zhang, Tianyu 1,2; Mei, Xiyu 1,2; Ouyang, Hao 1,2; Lu, Bin 1,2; Yu, Zengyang 1,2; Wang, Zhengtao 1,2; Ji, Lili 2,3
刊名	The Journal of nutritional biochemistry
	2018-12-04
卷号	65 页码:1-14
ISSN号	1873-4847
DOI	10.1016/j.jnutbio.2018.11.006
文献子类	Article
英文摘要	Hyperglycemia-induced blood-retinal barrier (BRB) breakdown is an early and typical event of diabetic retinopathy (DR). Although chronic inflammation plays an important role in DR development, the concrete mechanism remains unclear. This study aims to investigate the role of microglia cells-triggered inflammatory response in hyperglycemia-induced BRB breakdown and the amelioration of galangin, a natural flavonoid. Galangin alleviated BRB breakdown in streptozotocin-induced diabetic mice. D-glucose (25 mM)-stimulated microglia BV2 cells induced BRB damage in vitro, but galangin reversed this injury. Galangin decreased the activation of microglia cells, ROS formation, the phosphorylation of extracellular-signal-regulated protein kinase (ERK)1/2, the transcriptional activation of nuclear factor κB (NFκB) and early growth response (Egr1) protein, and the elevated expression of tumor necrosis factor (TNF)-α both in vitro and in vivo. ERK1/2 inhibitor U0126 reduced ROS formation, the activation of NFκB and Egr1, and the elevated TNFα expression in D-glucose-stimulated BV2 cells. N-acetylcysteine, a well-known antioxidant, abrogated D-glucose-induced NFκB and Egr1 activation in BV2 cells. Galangin also reversed the decreased expression of claudin1 and occludin, and the increased BRB injury and ROS formation in TNFα-treated human retinal endothelial cells (HRECs) and ARPE19 cells. Galangin induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in both HRECs and ARPE19 cells. Moreover, the galangin-provided attenuation on BRB breakdown was diminished in Nrf2 knockout diabetic mice. In conclusion, galangin alleviated DR by attenuating BRB damage via inhibiting microglia-triggered inflammation and further reversing TNFα-induced BRB dysfunction by abrogating oxidative stress injury via activating Nrf2.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266503]
专题	中国科学院上海药物研究所
通讯作者	Ji, Lili
作者单位	1.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; 2.The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; 3.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	Zhang, Tianyu,Mei, Xiyu,Ouyang, Hao,et al. Natural flavonoid galangin alleviates microglia-trigged blood-retinal barrier dysfunction during the development of diabetic retinopathy[J]. The Journal of nutritional biochemistry,2018,65:1-14.
APA	Zhang, Tianyu.,Mei, Xiyu.,Ouyang, Hao.,Lu, Bin.,Yu, Zengyang.,...&Ji, Lili.(2018).Natural flavonoid galangin alleviates microglia-trigged blood-retinal barrier dysfunction during the development of diabetic retinopathy.The Journal of nutritional biochemistry,65,1-14.
MLA	Zhang, Tianyu,et al."Natural flavonoid galangin alleviates microglia-trigged blood-retinal barrier dysfunction during the development of diabetic retinopathy".The Journal of nutritional biochemistry 65(2018):1-14.