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Int J Mol Sci. 2017 Feb 9;18(2). pii: E77. doi: 10.3390/ijms18020077.

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

Yang K1,2,3,4, Zhang H5,6,7,8, Luo Y9,10,11,12, Zhang J13,14,15,16, Wang M17,18,19,20, Liao P21, Cao L22,23,24,25, Guo P26,27,28,29, Sun G30,31,32,33, Sun X34,35,36,37.

Author information

1
Beijing 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, China. yangyongyao168@sina.com.
2
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. yangyongyao168@sina.com.
3
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. yangyongyao168@sina.com.
4
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. yangyongyao168@sina.com.
5
Beijing 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, China. hjzforever@126.com.
6
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. hjzforever@126.com.
7
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. hjzforever@126.com.
8
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. hjzforever@126.com.
9
Beijing 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, China. yluo@implad.ac.cn.
10
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. yluo@implad.ac.cn.
11
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. yluo@implad.ac.cn.
12
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. yluo@implad.ac.cn.
13
Beijing 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, China. zhangjingyi707@126.com.
14
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. zhangjingyi707@126.com.
15
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. zhangjingyi707@126.com.
16
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. zhangjingyi707@126.com.
17
Beijing 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, China. mwang@implad.ac.cn.
18
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. mwang@implad.ac.cn.
19
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. mwang@implad.ac.cn.
20
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. mwang@implad.ac.cn.
21
Department of Pharmacology, Guilin Medical University, Guilin 541000, Guangxi, China. liaoping555@163.com.
22
Beijing 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, China. lcao@implad.ac.cn.
23
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. lcao@implad.ac.cn.
24
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. lcao@implad.ac.cn.
25
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. lcao@implad.ac.cn.
26
Beijing 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, China. pguo@implad.ac.cn.
27
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. pguo@implad.ac.cn.
28
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. pguo@implad.ac.cn.
29
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. pguo@implad.ac.cn.
30
Beijing 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, China. gbsun@implad.ac.cn.
31
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. gbsun@implad.ac.cn.
32
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. gbsun@implad.ac.cn.
33
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. gbsun@implad.ac.cn.
34
Beijing 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, China. xbsun@implad.ac.cn.
35
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. xbsun@implad.ac.cn.
36
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. xbsun@implad.ac.cn.
37
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. xbsun@implad.ac.cn.

Abstract

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.

KEYWORDS:

apoptosis; atherosclerosis; estrogen receptors; gypenoside XVII; oxidative damage

PMID:
28208754
PMCID:
PMC5343768
DOI:
10.3390/ijms18020077
[Indexed for MEDLINE]
Free PMC Article

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