Absorption of resveratrol by vascular endothelial cells through passive diffusion and an SGLT1-mediated pathway.
Resveratrol is a natural polyphenol that exerts potent effects to suppress atherosclerosis. However, its low concentration in plasma has placed this role in doubt. Thus, resveratrol effects might be dependent on its transport into vascular endothelium, a question not previously addressed in spite of its obvious and fundamental importance. Via high-performance liquid chromatography and liquid chromatography/mass spectrometry, we found that resveratrol was absorbed by human umbilical vein endothelial cells in a temperature-, concentration- and time-dependent manner, suggesting the involvement of passive diffusion and active transport. As determined by confocal laser scanning microscopy, resveratrol primarily distributed throughout the cytoplasm. Furthermore, resveratrol absorption was modulated by serum proteins and sodium-dependent glucose transporter 1 (SGLT1) yet inhibited by glucose (an SGLT1 substrate) and phlorizin (an SGLT1 selective inhibitor), as well as SGLT1 siRNA transfection. Additionally, Sprague-Dawley rats were intragastrically administrated with 100mg/kg of resveratrol and the concentration of resveratrol in blood vessels declined more slowly up to 24h compared to that in the blood. Our results suggested that resveratrol uptake by vascular endothelial cells involved both passive diffusion and an SGLT1-mediated process, at least partially. Moreover, the intracellular resveratrol pool may be more important than the serum level in vivo. These provide new insights into the cardiovascular benefits of resveratrol.
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing 400038, People's Republic of China.
Ming-liang
ML
Chen
Long
L
Yi
Xin
X
Jin
Qi
Q
Xie
Ting
T
Zhang
Xi
X
Zhou
Hui
H
Chang
Yu-jie
YJ
Fu
Jun-dong
JD
Zhu
Qian-yong
QY
Zhang
Man-tian
MT
Mi
D000818:Animals; D004058:Diffusion; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D000077185:Resveratrol; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000378:metabolism*; D014162:Transfection
D051269:Sodium-Glucose Transporter 1; D013267:Stilbenes; D010695:Phlorhizin; D005947:Glucose; D000077185:Resveratrol
AS; Atherosclerosis; BSA; CLSM; DMSO; FBS; FITC; HPLC; HUVEC; LC/MS; MRM; PBS; Resveratrol; SGLT1; SIRT1; Sodium-dependent glucose transporter; Transmembrane transport; Vascular endothelial cells; atherosclerosis; bovine serum albumin; confocal laser scanning microscopy; dimethyl sulfoxide; fetal bovine serum; fluorescein isothiocyanate; high-performance liquid chromatography; human umbilical vein endothelial cell; liquid chromatography/mass spectrometry; multiple reaction monitoring; phosphate-buffered saline; silent mating type information regulation 2 homolog 1; sodium-dependent glucose transporter 1