title: Involvement of androgen receptor in nitric oxide production induced by icariin in human umbilical vein endothelial cells.
abstract: Icariin, a flavonoid isolated from Epimedii herba, stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177, Akt (Ser473) and ERK1/2 (Thr202/Tyr204). The icariin-induced eNOS phosphorylation was abolished by an androgen receptor (AR) antagonist, nilutamide in human umbilical vein endothelial cells (HUVECs). Furthermore, it was also reduced in the cells transfected with small interfering RNA in which the expression of AR was broken down. The icariin-induced eNOS phosphorylation was inhibited by wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. These data suggest that icariin stimulates release of NO by AR-dependent activation of eNOS in HUVECs. PI3K/Akt and MAPK-ERK kinase (MEK)/ERK1/2 pathways were involved in the phosphorylation of eNOS by icariin.
authors.affiliation: Department of Integrated Traditional Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Koizumi
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Ryo
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Okabe
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D005419:Flavonoids; D048289:Imidazolidines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011944:Receptors, Androgen; D009569:Nitric Oxide; C021277:nilutamide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C056599:icariin; D000077191:Wortmannin