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

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

  • Int J Mol Sci. 2017 Feb 9;18(2):77. doi: 10.3390/ijms18020077.
Ke Yang 1 2 3 4,  Haijing Zhang 5 6 7 8,  Yun Luo 9 10 11 12,  Jingyi Zhang 13 14 15 16,  Min Wang 17 18 19 20,  Ping Liao 21,  Li Cao 22 23 24 25,  Peng Guo 26 27 28 29,  Guibo Sun 30 31 32 33,  Xiaobo Sun 34 35 36 37
Affiliations

Affiliations

  • 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. [email protected].
  • 2 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 3 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 4 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 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. [email protected].
  • 6 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 7 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 8 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 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. [email protected].
  • 10 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 11 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 12 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 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. [email protected].
  • 14 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 15 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 16 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 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. [email protected].
  • 18 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 19 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 20 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 21 Department of Pharmacology, Guilin Medical University, Guilin 541000, Guangxi, China. [email protected].
  • 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. [email protected].
  • 23 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 24 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 25 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 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. [email protected].
  • 27 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 28 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 29 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 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. [email protected].
  • 31 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 32 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 33 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 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. [email protected].
  • 35 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 36 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 37 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
PMID: 28208754 DOI: 10.3390/ijms18020077
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.

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