Biomol Ther  
Endothelium Independent Effect of Pelargonidin on Vasoconstriction in Rat Aorta
Young Sil Min1,†, Hyuk-Jun Yoon2,†, Hyun Dong Je2, Jong Hyuk Lee3, Seong Su Yoo4, Hyun Sub Shim4, Hak Yeong Lee4, Hyen-Oh La5,* and Uy Dong Sohn4,*
1Department of Medical Plant Science, College of Scienceand Engineering, Jung Won University, Goesan 28024,
2Department of Pharmacology, College of Pharmacy, Catholic University of Daegu, Gyeongsan 38430,
3Department of Pharmaceutical Engineering, College of Life and Health Science, Hoseo University, Asan 31499,
4Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 06974, 5Department of Clinical Pharmacology, College of Pharmacy, Catholic University of Korea, Bucheon 14662, Republic of Korea
E-mail: hola@catholic.ac.kr (La HO), udsohn@cau.ac.kr (Sohn UD)
Tel: +82-2-2164-6598 (La HO), +82-2-820-5614 (Sohn UD)
Fax: +82-2-2164-6598 (La HO), +82-2-826-8752 (Sohn UD)
The first two authors contributed equally to this work.
Received: September 29, 2017; Revised: December 18, 2017; Accepted: December 21, 2017; Published online: February 1, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
In this study, we investigated the effects of pelargonidin, an anthocyanidin found in many fruits and vegetables, on endotheliumindependent vascular contractility to determine the underlying mechanism of relaxation. Isometric contractions of denuded aortic muscles from male rats were recorded, and the data were combined with those obtained in western blot analysis. Pelargonidin significantly inhibited fluoride-, thromboxane A2-, and phorbol ester-induced vascular contractions, regardless of the presence or absence of endothelium, suggesting a direct effect of the compound on vascular smooth muscles via a different pathway. Pelargonidin significantly inhibited the fluoride-dependent increase in the level of myosin phosphatase target subunit 1 (MYPT1) phosphorylation at Thr-855 and the phorbol 12,13-dibutyrate-dependent increase in the level of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at Thr202/Tyr204, suggesting the inhibition of Rho-kinase and mitogen-activated protein kinase kinase (MEK) activities and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxation effect of pelargonidin on agonist-dependent vascular contractions includes inhibition of Rho-kinase and MEK activities, independent of the endothelial function.
Keywords: ERK1/2, Fluoride, MYPT1, Pelargonidin, Phorbol ester, Rho-kinase


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