PUBLICATION
Diphlorethohydroxycarmalol Isolated from Ishige okamurae Exerts Vasodilatory Effects via Calcium Signaling and PI3K/Akt/eNOS Pathway
- Authors
- Lu, Y.A., Jiang, Y., Yang, H.W., Hwang, J., Jeon, Y.J., Ryu, B.
- ID
- ZDB-PUB-210211-4
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(4): (Journal)
- Registered Authors
- Jeon, You-Jin
- Keywords
- Acetylcholine receptor, Calcium, Diphlorethohydroxycarmalol, NO production, VEGFR2, Vasodilation
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Calcium Signaling/drug effects*
- Cell Line
- Endothelial Cells/drug effects
- Endothelial Cells/metabolism
- Heterocyclic Compounds, 3-Ring/isolation & purification
- Heterocyclic Compounds, 3-Ring/pharmacology*
- Humans
- Nitric Oxide/biosynthesis
- Nitric Oxide Synthase Type III/metabolism
- Phaeophyceae/chemistry*
- Phosphatidylinositol 3-Kinases/metabolism
- Proto-Oncogene Proteins c-akt/metabolism
- Receptors, Cholinergic/metabolism
- Signal Transduction/drug effects
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Vasodilation/drug effects
- Vasodilator Agents/isolation & purification
- Vasodilator Agents/pharmacology*
- Zebrafish
- PubMed
- 33562632 Full text @ Int. J. Mol. Sci.
Citation
Lu, Y.A., Jiang, Y., Yang, H.W., Hwang, J., Jeon, Y.J., Ryu, B. (2021) Diphlorethohydroxycarmalol Isolated from Ishige okamurae Exerts Vasodilatory Effects via Calcium Signaling and PI3K/Akt/eNOS Pathway. International Journal of Molecular Sciences. 22(4):.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping