Open AccessThe Protective Effect of Tetrahydroxystilbene Glucoside on High Glucose-Induced Injury in Human Umbilical Vein Endothelial Cells through the PI3K/Akt/eNOS Pathway and Regulation of Bcl-2/Bax
Author(s) -
Jiankun Cui,
Bo Zhang,
Min Gao,
Baohai Liu,
Cong Dai,
Dong Yan,
Fanji Meng
Publication year - 2021
Publication title -
journal of vascular research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.58
H-Index - 74
eISSN - 1423-0135
pISSN - 1018-1172
DOI - 10.1159/000511035
Subject(s) - enos , umbilical vein , ly294002 , protein kinase b , apoptosis , pi3k/akt/mtor pathway , nitric oxide , reactive oxygen species , downregulation and upregulation , nitric oxide synthase , chemistry , biology , pharmacology , medicine , endocrinology , biochemistry , in vitro , gene
Endothelial dysfunction plays a central role in the pathogenesis of diabetic vascular complications. 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from the roots of Polygonum multiflorum Thunb, has been shown to have strong antioxidant and antiapoptotic activities. In the present study, we investigated the protective effect of TSG on apoptosis induced by high glucose in human umbilical vein endothelial cells (HUVECs) and the possible mechanisms. Our data demonstrated that TSG significantly reversed the high glucose-induced decrease in cell viability, suppressed high glucose-induced generation of intracellular reactive oxygen species (ROS), the activity of caspase-3, and decreased the percentage of apoptotic cells in a dose-dependent manner. In addition, we found that TSG not only increased the expression of Bcl-2, while decreasing Bax expression, but also activated phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) with subsequent nitric oxide production and ultimately reduced high glucose-induced apoptosis. However, the antiapoptotic effects of TSG were abrogated by pretreatment of the cells with PI3K inhibitor (LY294002) or eNOS inhibitor N G -L-nitro-arginine methyl ester, respectively. These results suggest that TSG inhibits high glucose-induced apoptosis in HUVECs through inhibition of ROS production, activation of the PI3K/Akt/eNOS pathway, and upregulation of the Bcl-2/Bax ratio, and thus may demonstrate significant potential for preventing diabetic cardiovascular complications.