Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway  

作　　者：Ke-Xin Sun Yan-Yi Chen Zhen Li Shi-Jie Zheng Wen-Juan Wan Yan Ji Ke Hu 

机构地区：[1]Department of Ophthalmology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]Department of Ophthalmology,The People’s Hospital of Leshan,Leshan 400000,Sichuan Province,China

出　　处：《World Journal of Diabetes》2023年第9期1349-1368,共20页世界糖尿病杂志（英文版）（电子版）

基　　金：the National Natural Science Foundation of China,No.81870650,No.81570832,and No.81900885;Science and Technology Program Chongqing,No.2018GDRC008 and No.XKTS049。

摘　　要：BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced glycation end products(AGEs)and their cell toxicity can be a useful therapeutic strategy in the prevention of diabetic retinopathy(DR).Gardenia jasminoides Ellis(GJE)fruit is a selective inhibitor of AGEs.Genipin is an active compound of GJE fruit,which can be employed to treat diabetes.AIM To confirm the effect of genipin,a vital component of GJE fruit,in preventing human retinal microvascular endothelial cells(hRMECs)from AGEs damage in DR,to investigate the effect of genipin in the down-regulation of AGEs expression,and to explore the role of the CHGA/UCP2/glucose transporter 1(GLUT1)signal pathway in this process.METHODS In vitro,cell viability was tested to determine the effects of different doses of glucose and genipin in hRMECs.Cell Counting Kit-8(CCK-8),colony formation assay,flow cytometry,immunofluorescence,wound healing assay,transwell assay,and tube-forming assay were used to detect the effect of genipin on hRMECs cultured in high glucose conditions.In vivo,streptozotocin(STZ)induced mice were used,and genipin was administered by intraocular injection(IOI).To explore the effect and mechanism of genipin in diabetic-induced retinal dysfunction,reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose(2-NBDG)assays were performed to explore energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas.Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines[vascular endothelial growth factor(VEGF),SCG3,tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-18,and nucleotide-binding domain,leucine-rich-containing family,pyrin domain-containing 3(NLRP3)].The protein expression of the receptor of AGEs(RAGE)and the mitochondria-related s

关 键 词：GENIPIN Human retinal microvascular endothelial cells ANGIOGENESIS VASCULARIZATION Secretogranin III Diabetic retinopathy 

分 类 号：R587.2[医药卫生—内分泌]