Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent glucose transporter SGLT1

• Published in: PloS one Vol. 8; no. 7; p. e68617
• Main Authors: Jin, Xin, Yi, Long, Chen, Ming-liang, Chen, Chun-ye, Chang, Hui, Zhang, Ting, Wang, Li, Zhu, Jun-dong, Zhang, Qian-yong, Mi, Man-tian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18-07-2013; Public Library of Science (PLoS)
• Subjects: Analysis of Variance; Animals; Anthocyanins; Anthocyanins - chemistry; Anthocyanins - pharmacology; Antioxidants; Apoptosis; Apoptosis - drug effects; Apoptosis-inducing factor; Arteriosclerosis; Atherosclerosis; Bcl-2 protein; Bioactive compounds; Bioavailability; Biology; Blotting, Western; Cardiovascular disease; Caspase-3; Cell proliferation; Cell Proliferation - drug effects; Chemistry; Chromatography, High Pressure Liquid; Cytochrome; Cytochrome c; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Female; Flow Cytometry; Food safety; Formazans; Fruits; Glucose; Glucose transporter; Glucosides - chemistry; Glucosides - pharmacology; Human Umbilical Vein Endothelial Cells; Humans; Laboratories; Lipoproteins; Lipoproteins, LDL - toxicity; Low density lipoproteins; Medicine; Membrane permeability; Membrane potential; Metabolism; Mice; Mice, Inbred BALB C; Mitochondria; Mitochondrial Diseases - chemically induced; Mitochondrial Diseases - drug therapy; Mitochondrial permeability transition pore; Molecular modelling; Molecular Structure; Nutrition research; Oxidative stress; Oxygen; Permeability; Plants (botany); Polyphenols; Preventive medicine; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rodents; siRNA; Sodium; Sodium-Glucose Transporter 1 - metabolism; Spectrometry, Fluorescence; Substrate inhibition; Superoxides; Tetrazolium Salts; Umbilical vein; Vegetables
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068617

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.