title: Pretreatment with Astragaloside IV protects human umbilical vein endothelial cells from hydrogen peroxide induced oxidative stress and cell dysfunction via inhibiting eNOS uncoupling and NADPH oxidase - ROS - NF-κB pathway.
abstract: Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular disorders. Astragaloside IV (AsIV) possesses potent antioxidant properties against oxidative stress through undefined mechanism(s). We sought to investigate whether AsIV protects human umbilical vein endothelial cells (HUVECs) from hydrogen peroxide (H2O2) induced oxidative stress focusing on eNOS uncoupling and the NADPH oxidase - ROS - NF-κB pathway. Compared with HUVECs incubated with H2O2alone, pretreatment with AsIV significantly increased the viability of HUVECs, which was accompanied with apparent increase in nitric oxide (NO) production and decrease in intracellular superoxide anion production. Furthermore, pretreatment with AsIV increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (BH4) content, decreased Nox4 protein expression (the most abundant Nox isoform in HUVECs), inhibited translocation of NF-κB p65 subunit into nuclear fraction while enhanced the protein expression of IκB-α (the inhibitor of NF-κB p65), reduced the levels of IL-1β, IL-6, and TNF-α in HUVECs medium, and decreased iNOS protein expression. These results suggest that AsIV may protect HUVECs from H2O2-induced oxidative stress via inhibiting NADPH oxidase - ROS - NF-κB pathway and eNOS uncoupling.
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Chonghua
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Futian
authors.initials: F
authors.lastname: Tang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Lu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Ronghui
authors.initials: R
authors.lastname: Han
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Mei
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.|Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
keywords: Astragaloside IV; NADPH oxidase; NADPH oxydase; NF-κB; anion superoxyde; astragaloside IV; cellules endothéliales des veines ombilicales humaines; découplage de l’eNOS; eNOS uncoupling; human umbilical vein endothelial cells; hydrogen peroxide; peroxyde d’hydrogen; superoxide anion; tetrahydrobiopterin; tétrahydrobioptérine