A novel antihypertension agent, sargachromenol D from marine brown algae, Sargassum siliquastrum, exerts dual action as an L-type Ca2+ channel blocker and endothelin A/B-2 receptor antagonist

作者：Park Byong Gon; Shin Woon Seob; Oh Sangtae; Park Gab Man; Kim Nam Ik; Lee Seokjoon^*

来源：Bioorganic & Medicinal Chemistry, 2017, 25(17): 4649-4655.

DOI：10.1016/j.bmc.2017.07.002

• Marine natural product
• Isolation
• Vasodilation
• Severe hypertension
• Endotheline-1
• L-type Ca2+ channel blocker
• Endothelin A/B-2 receptor antagonist

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 (50 mM K+)-induced basilar artery contraction with EC50 values of 3.52 +/- 0.42 and 1.62 +/- 0.63 lM, respectively, but only sargachromenol D (5) showed a vasodilatory effect on endothelin-1 (ET-1)-induced basilar artery contraction (EC50 = 9.8 +/- 0.6 mu M). These results indicated that sargachromenol D (5) could act as a dual antagonist of L-type Ca2+ channel and endothelin A/B-2 receptors. Moreover, sargachromenol D (5) lowered blood pressure in spontaneous hypertensive rats (SHRs) 2 h after oral treatment at a dose of 80 mg/kg dose and the effect was maintained for 24 h. 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.

• 出版日期2017-9-1