A novel antihypertension agent, sargachromenol D from marine brown algae, Sargassum siliquastrum, exerts dual action as an L-type Ca 2+ channel blocker and endothelin A/B 2 receptor antagonist.

Autor: Park BG; Department of Physiology, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea; Institute for Clinical and Translational Research, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea., Shin WS; Institute for Clinical and Translational Research, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea; Department of Microbiology, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea., Oh S; Department of Basic Science, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea., Park GM; Institute for Clinical and Translational Research, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea; Department of Environmental Medical Biology, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea., Kim NI; Department of Physical Education, Catholic Kwandong University College of Education, Gangneung 25601, Republic of Korea., Lee S; Institute for Clinical and Translational Research, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea; Department of Pharmacology, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea. Electronic address: sjlee@cku.ac.kr.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2017 Sep 01; Vol. 25 (17), pp. 4649-4655. Date of Electronic Publication: 2017 Jul 06.
DOI: 10.1016/j.bmc.2017.07.002
Abstrakt: We isolated the novel vasoactive marine natural products, (5E,10E)-14-hydroxy-2,6,10-trimethylpentadeca-5,10-dien-4-one (4) and sargachromenol D (5), from Sargassum siliquastrum collected from the coast of the East Sea in South Korea by using activity-guided HPLC purification. The compounds effectively dilated depolarization (50mMK + )-induced basilar artery contraction with EC 50 values of 3.52±0.42 and 1.62±0.63μM, respectively, but only sargachromenol D (5) showed a vasodilatory effect on endothelin-1 (ET-1)-induced basilar artery contraction (EC 50 =9.8±0.6μM). These results indicated that sargachromenol D (5) could act as a dual antagonist of l-type Ca 2+ channel and endothelin A/B 2 receptors. Moreover, sargachromenol D (5) lowered blood pressure in spontaneous hypertensive rats (SHRs) 2h after oral treatment at a dose of 80mg/kg dose and the effect was maintained for 24h. Based on our ex vivo and in vivo experiments, we propose that sargachromenol D (5) is a strong candidate for the treatment of hypertension that is not controlled by conventional drugs, in particular, severe-, type II diabetes-, salt-sensitive, and metabolic disease-induced hypertension.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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