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Mulberry Extract Attenuates Endothelial Dysfunction through the Regulation of Uncoupling Endothelial Nitric Oxide Synthase in High Fat Diet Rats

1
Non-Clinical Evaluation Center, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju 54907, Chonbuk, Korea
2
Clinical Trial Center for Functional Foods (CTCF2), Chonbuk National University Hospital, Jeonju 54907, Chonbuk, Korea
3
Department of Pharmacology, Chonbuk National University Medical School, Jeonju 54896, Chonbuk, Korea
4
Institute of New Drug Development, School of Medicine, Chonbuk National University, Jeonju 54907, Chonbuk, Korea
*
Authors to whom correspondence should be addressed.
Nutrients 2019, 11(5), 978; https://doi.org/10.3390/nu11050978
Received: 19 March 2019 / Revised: 24 April 2019 / Accepted: 25 April 2019 / Published: 28 April 2019
Dyslipidemia is associated with endothelial dysfunction, which is linked to nitric oxide (NO) biology. The coupling of endothelial NO synthase with cofactors is a major step for NO release. This study is aimed to investigate the vascular pharmacology effects of mulberry in rat thoracic aorta and human vascular endothelial cells. In vitro, we investigated the protective effects of the mulberry extract and its main component cyanidin-3-rutinoside (C-3-R), against oxidized low-density lipoprotein (ox-LDL)-induced endothelial nitric oxide synthase (eNOS) uncoupling. Whereas ox-LDL significantly decreased NO levels in endothelial cells, mulberry extract, and C-3-R significantly recovered NO levels and phospho-eNOS Thr495 and Ser1177 expression. In vivo, mulberry was administered to 60% of high-fat diet (w/w)-fed Sprague Dawley (SD) rats for six weeks, in which endothelium-dependent relaxations were significantly improved in organ bath studies and isometric tension recordings. Consistently, aortic expressions of phospho-eNOS and nitrotyrosine were increased. Mulberry also raised serum NO levels, increased phosphorylation of eNOS, and reduced nitrotyrosine and intracellular reactive oxygen species (ROS) in aortas, showing that mulberry preserves endothelium-dependent relaxation in aortas from high-fat diet rats. We suggest that this effect is mediated through enhanced NO bioavailability, in which the regulation of ROS and its reduced eNOS uncoupling are involved. View Full-Text
Keywords: mulberry; vascular function; high-fat diet; HUVECs mulberry; vascular function; high-fat diet; HUVECs
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Lee, G.-H.; Hoang, T.-H.; Jung, E.-S.; Jung, S.-J.; Chae, S.-W.; Chae, H.-J. Mulberry Extract Attenuates Endothelial Dysfunction through the Regulation of Uncoupling Endothelial Nitric Oxide Synthase in High Fat Diet Rats. Nutrients 2019, 11, 978.

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