title: Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent glucose transporter SGLT1.
abstract: Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.forename: Ming-liang
authors.initials: ML
authors.lastname: Chen
authors.forename: Chun-ye
authors.initials: CY
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Chang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jun-dong
authors.initials: JD
authors.lastname: Zhu
authors.forename: Qian-yong
authors.initials: QY
authors.lastname: Zhang
authors.forename: Man-tian
authors.initials: MT
authors.lastname: Mi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005562:Formazans; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013778:Tetrazolium Salts
chemical_list: D000872:Anthocyanins; D005562:Formazans; D005960:Glucosides; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D013778:Tetrazolium Salts; C099252:oxidized low density lipoprotein; C079782:MTT formazan; C494120:delphinidin 3-O-glucopyranoside