Open AccessEchinacoside‑induced nitric oxide production in endothelial�cells: Roles of androgen receptor and the PI3K‑Akt pathway
Author(s) -
Li Gu,
Danhong Lian,
Yaguang Zheng,
Wei Zhou,
Jinlei Gu,
Xin Liu
Publication year - 2020
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2020.4476
Subject(s) - enos , wortmannin , protein kinase b , pi3k/akt/mtor pathway , nitric oxide , phosphorylation , umbilical vein , endothelium , microbiology and biotechnology , chemistry , kinase , medicine , nitric oxide synthase , biology , endocrinology , signal transduction , biochemistry , in vitro
Echinacoside (ECH) is a natural compound with an endothelium‑dependent vasodilatory effect. Nitric oxide (NO) is an important vasorelaxant released from endothelial cells. In order to examine the molecular mechanism of ECH‑induced NO production in endothelial cells, the present study investigated the involvement of androgen receptor (AR) and the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) pathway in the phosphorylation of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs). Using the fluorescent probe DAF‑FM, the production of NO was found to be significantly increased, and eNOS was phosphorylated at Ser1177 in a concentration‑dependent manner under 0.01‑10 µM ECH treatment in HUVECs. In addition, NO production and eNOS phosphorylation induced by ECH were diminished when pretreated with the AR antagonist nilutamide, or when transfected with AR small interfering RNAs. Furthermore, the ECH‑induced phosphorylation of the Akt at Ser473 was abrogated by 5 µM wortmannin (a PI3K inhibitor). These data indicated that ECH stimulated NO production via the AR‑dependent activation of eNOS in HUVECs, and that the PI3K/Akt pathway may be involved in eNOS phosphorylation induced by ECH.