Diphlorethohydroxycarmalol Isolated from Ishige okamurae Exerts Vasodilatory Effects via Calcium Signaling and PI3K/Akt/eNOS Pathway

Abstract

Nitric oxide (NO) is released by endothelial cells in the blood vessel wall to enhance vasodilation. Marine polyphenols are known to have protective effects against vascular dysfunction and hypertension. The present study is the first to investigate how diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae affects calcium levels, resulting in enhanced vasodilation. We examined calcium modulation with the well-known receptors, acetylcholine receptor (AchR) and vascular endothelial growth factor 2 (VEGFR2), which are related to NO formation, and further confirmed the vasodilatory effect of DPHC. We confirmed that DPHC stimulated NO production by increasing calcium levels and endothelial nitric oxide synthase (eNOS) expression. DPHC affected AchR and VEGFR2 expression, thereby influencing transient calcium intake. Specific antagonists, atropine and SU5416, were used to verify our findings. Furthermore, based on the results of in vivo experiments, we treated Tg(flk:EGFP) transgenic zebrafish with DPHC to confirm its vasodilatory effect. In conclusion, the present study showed that DPHC modulated calcium transit through AchR and VEGFR2, increasing endothelial-dependent NO production. Thus, DPHC, a natural marine component, can efficiently ameliorate cardiovascular diseases by improving vascular function.

Macrophage-like THP-1 Cells Derived from High-Density Cell Culture Are Resistant to TRAIL-Induced Cell Death via Down-Regulation of Death-Receptors DR4 and DR5

“…To assess the intracellular NO activity, cells were stained with 5 μM DAF-FM DA [ 29 ] and incubated for 40 min in a CO 2 -incubator. Then, they were washed with a fresh growth medium and incubated for an additional 30 min in a CO 2 -incubator.…”

Therapeutic Potential of Seaweed-Derived Bioactive Compounds for Cardiovascular Disease Treatment

“…These actions would reduce the phosphorylation of the Ca 2+sensitive myosin light chains, resulting in vasodilation [34]. One study demonstrated that Lu et al used the EA.hy926 cells and zebrafish model to systematically establish the potential mechanisms of the vasodilation produced by diekol and diphlorethohydroxycarmalol isolated from Ecklonia cava (E. cava) and Ishige okamurae (I. okamurae) [35,36] (Table 1). In addition, four major phlorotannins-dieckol, 2,7-phloroglucinol-6,6-bieckol, phlorofucofuroeckol A, and pyrogallol-phloroglucinol-6,6-bieckol-isolated from Ecklonia cava effectively inhibited monocyte-associated vascular inflammation and dysfunction by suppressing monocyte migration and protecting monocyte-associated endothelial cell death [37].…”

“…In addition, four major phlorotannins-dieckol, 2,7-phloroglucinol-6,6-bieckol, phlorofucofuroeckol A, and pyrogallol-phloroglucinol-6,6-bieckol-isolated from Ecklonia cava effectively inhibited monocyte-associated vascular inflammation and dysfunction by suppressing monocyte migration and protecting monocyte-associated endothelial cell death [37]. Moreover, pyrogallol-phloroglucinol-6,6 -bieckol and dieckol isolated from E. Cava have been shown to improve blood circulation in mice fed diets to induce obesity and hypertension [36,38]. Therefore, while numerous factors contribute to hypertension, it is well recognized that an increased vascular tone is always the ultimate goal.…”

Seaweeds and Their Natural Products for Preventing Cardiovascular Associated Dysfunction

“…They suggested that the abundance of hydroxyl groups of eckol and its derivatives contribute to their vascular barrier protective functions. Another phlorotannin, diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae , was observed to have vasodilatory effects by increasing nitric oxide production and Ca 2+ release in endothelial cells via stimulating the Ach receptor and VEGF-receptor 2 [ 46 ]. The author further demonstrated the vasodilatory ability of DPHC in Tg(flk:EGFP) transgenic zebrafish.…”