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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2017-02-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | http://www.mdpi.com/1422-0067/18/2/77 |
id |
doaj-68f1716fcd1940058ebc379c26a32073 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ke Yang Haijing Zhang Yun Luo Jingyi Zhang Min Wang Ping Liao Li Cao Peng Guo Guibo Sun Xiaobo Sun |
spellingShingle |
Ke Yang Haijing Zhang Yun Luo Jingyi Zhang Min Wang Ping Liao Li Cao Peng Guo Guibo Sun Xiaobo Sun Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway International Journal of Molecular Sciences gypenoside XVII estrogen receptors atherosclerosis oxidative damage apoptosis |
author_facet |
Ke Yang Haijing Zhang Yun Luo Jingyi Zhang Min Wang Ping Liao Li Cao Peng Guo Guibo Sun Xiaobo Sun |
author_sort |
Ke Yang |
title |
Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway |
title_short |
Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway |
title_full |
Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway |
title_fullStr |
Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway |
title_full_unstemmed |
Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway |
title_sort |
gypenoside xvii prevents atherosclerosis by attenuating endothelial apoptosis and oxidative stress: insight into the erα-mediated pi3k/akt pathway |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-02-01 |
description |
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. |
topic |
gypenoside XVII estrogen receptors atherosclerosis oxidative damage apoptosis |
url |
http://www.mdpi.com/1422-0067/18/2/77 |
work_keys_str_mv |
AT keyang gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT haijingzhang gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT yunluo gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT jingyizhang gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT minwang gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT pingliao gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT licao gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT pengguo gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT guibosun gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway AT xiaobosun gypenosidexviipreventsatherosclerosisbyattenuatingendothelialapoptosisandoxidativestressinsightintotheeramediatedpi3kaktpathway |
_version_ |
1725278062844575744 |
spelling |
doaj-68f1716fcd1940058ebc379c26a320732020-11-25T00:43:28ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-02-011827710.3390/ijms18020077ijms18020077Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt PathwayKe Yang0Haijing Zhang1Yun Luo2Jingyi Zhang3Min Wang4Ping Liao5Li Cao6Peng Guo7Guibo Sun8Xiaobo Sun9Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaDepartment of Pharmacology, Guilin Medical University, Guilin 541000, Guangxi, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, ChinaPhytoestrogens 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.http://www.mdpi.com/1422-0067/18/2/77gypenoside XVIIestrogen receptorsatherosclerosisoxidative damageapoptosis |