Objective Anthocyanins are potent antioxidant involved in preventing oxidative stress-induced endothelial dysfunction,a critical step in the initiation of atherosclerosis.However,the benefits appear to be in striking contrast with their poor bioavailability,unless attributable to yet unidentified transmembrane transport and tissue accumulation.Thus,the mechanisms by which anthocyanins were absorbed by endothelium needs to be assessed.Methods and results In this study,we reports significant advances on the transport of delphinidin-3-glucoside (Dp),a natural anthocyanin widely presents in pigmented plant food in human endothelial cell EA.hy926.Furthermore,the involvement of the membrane transporter sodium-dependent glucose transporter (SGLT1) as the key underlying molecular mechanism for the transport and bioactivities were investigated.Based on the autofluorescence property,Dp can be absorbed and might have mitochondriotropic distribution in EA.hy926 cells.And the passive uptake was significantly inhibited by bovine serum albumin,while the active transport was noticeably dependent on SGLT1,yet inhibited by glucose,a substrate of SGLT1,and phlorizin,a competitive inhibitor of SGLT1 and also SGLT1 siRNA transfection,respectively.Additionally,SGLT1 activity was essential for the inhibitive effects of Dp on mitochondrial dysfunction,measured by the superoxide scavenging activity,mituchondrial membrane potential (ΔΨm),mitochondrial permeability transition pore (mPTP) opening and the expression of apoptosis-related proteins apoptosis-inducing factor (AIF),cytochrome c (Cyt c),bcl-2,bax and caspase-3.Conclusion These findings suggest that anthocyanins,despite their fast metabolism and very low bioavailability,might exertthe protective activity on endothelial finction through the mitochondriotropic antioxidant pathway.And SGLT1 is thereby a major factor in the prevention of atherosclerosis.