Cargando…

Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway

Phytoestrogens are estrogen-like compounds of plant origin. The pharmacological activities of phytoestrogens are predominantly due to their antioxidant, anti-inflammatory and lipid-lowering properties, which are mediated via the estrogen receptors (ERs): estrogen receptor alpha (ERα) and estrogen re...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Ke, Zhang, Haijing, Luo, Yun, Zhang, Jingyi, Wang, Min, Liao, Ping, Cao, Li, Guo, Peng, Sun, Guibo, Sun, Xiaobo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343768/
https://www.ncbi.nlm.nih.gov/pubmed/28208754
http://dx.doi.org/10.3390/ijms18020077
Descripción
Sumario:Phytoestrogens are estrogen-like compounds of plant origin. The pharmacological activities of phytoestrogens are predominantly due to their antioxidant, anti-inflammatory and lipid-lowering properties, which are mediated via the estrogen receptors (ERs): estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) and possibly G protein-coupled estrogen receptor 1 (GPER). Gypenoside XVII (GP-17) is a phytoestrogen that is widely used to prevent cardiovascular disease, including atherosclerosis, but the mechanism underlying these therapeutic effects is largely unclear. This study aimed to assess the anti-atherogenic effects of GP-17 and its mechanisms in vivo and in vitro. In vivo experiments showed that GP-17 significantly decreased blood lipid levels, increased the expression of antioxidant enzymes and decreased atherosclerotic lesion size in ApoE−/− mice. In vitro experiments showed that GP-17 significantly prevented oxidized low-density lipoprotein (Ox-LDL)-induced endothelial injury. The underlying protective mechanisms of GP-17 were mediated by restoring the normal redox state, up-regulating of the ratio of Bcl-2 to Bax and inhibiting the expression of cleaved caspase-3 in Ox-LDL-induced human umbilical vein endothelial cell (HUVEC) injury. Notably, we found that GP-17 treatment predominantly up-regulated the expression of ERα but not ERβ. However, similar to estrogen, the protective effect of GP-17 could be blocked by the ER antagonist ICI182780 and the phosphatidylinositol 3-kinase (PI3K) antagonist LY294002. Taken together, these results suggest that, due to its antioxidant properties, GP-17 could alleviate atherosclerosis via the ERα-mediated PI3K/Akt pathway.