Absorption of resveratrol by vascular endothelial cells through passive diffusion and an SGLT1-mediated pathway |
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Authors: | Ming-liang Chen Long Yi Xin Jin Qi Xie Ting Zhang Xi Zhou Hui Chang Yu-jie Fu Jun-dong Zhu Qian-yong Zhang Man-tian Mi |
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Institution: | 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 |
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Abstract: | 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 100 mg/kg of resveratrol and the concentration of resveratrol in blood vessels declined more slowly up to 24 h 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. |
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