%0 Journal Article %A Tran Thi Hien %A Won Keun Oh %A Phi Hung Nguyen %A Seok Jeong Oh %A Moo Yeol Lee %A Keon Wook Kang %T Nectandrin B Activates Endothelial Nitric-Oxide Synthase Phosphorylation in Endothelial Cells: Role of the AMP-Activated Protein Kinase/Estrogen Receptor α/Phosphatidylinositol 3-kinase/Akt Pathway %D 2011 %R 10.1124/mol.111.073502 %J Molecular Pharmacology %P 1166-1178 %V 80 %N 6 %X We revealed previously that nectandrin B isolated from Myristica fragrans (nutmeg, Myristicaceae) functions as a potent AMP-activated protein kinase (AMPK) activator and showed its antiobesity effect. In this study, we investigated whether nectandrin B affects phosphorylation of endothelial nitric-oxide synthase (eNOS) in human endothelial cells. Nectandrin B increased the phosphorylation of eNOS and nitric oxide (NO) production in a concentration-dependent manner and maximal effect was found at 10 μg/ml. Nectandrin B activates AMPK, presumably via Ca2+/calmodulin kinase II activation and nectandrin B-stimulated eNOS phosphorylation was reversed by AMPK inhibition. Both the enzyme activity of phosphatidylinositol 3-kinase (PI3K) and the estrogen receptor (ER)-dependent reporter gene transcription were enhanced by nectandrin B. ERα inhibition by specific antagonist or small interfering siRNA (siRNA) suppressed nectandrin B-mediated eNOS phosphorylation. Moreover, AMPK inhibition significantly reversed the activation of ER-dependent transcription and PI3K activation in response to nectandrin B. Nectandrin B evoked endothelium-dependent relaxation in rat aortic rings, and this was blocked by inhibition of AMPK, ER, or PI3K. These results suggest that potent AMPK activator nectandrin B enhances NO production via eNOS phosphorylation in endothelial cells and ERα-dependent PI3K activity is required. %U https://molpharm.aspetjournals.org/content/molpharm/80/6/1166.full.pdf