Ginsenoside Rb1 Prevents Dysfunction of Endothelial Cells by Suppressing Inflammatory Response and Apoptosis in the High-Fat Diet Plus Balloon Catheter-Injured Rabbit Model via the G Protein-Coupled Estrogen Receptor-Mediated Phosphatidylinositol 3-Kinases (PI3K)/Akt Pathway.

Abstract

<strong>BACKGROUND</strong> The initiation of atherosclerosis (AS) is attributed to the dysfunction of endothelial cells (ECs) via the inhibition of g protein-coupled estrogen receptor (GPER). In the current study, we assessed the potential of Ginsenoside Rb1 (Rb1) to attenuate the dysfunction of ECs via GPER-mediated PI3K/Akt pathway. <strong>MATERIAL AND METHODS</strong> AS was induced in rabbits and then the AS rabbits were treated with Rb1. Thereafter, the ECs were isolated from AS and healthy rabbits, and treated with Rb1. The effect of Rb1 on blood lipid levels in AS rabbits and on apoptosis, inflammatory response, and GPER/PI3K/Akt axis activity in ECs was detected. Furthermore, the activities of GPER and PI3K were modulated to verify the key role of the axis in the anti-AS effect of Rb1. <strong>RESULTS</strong> The levels of total cholesterol, low-density lipoprotein (LDL), and triglyceride in AS rabbits were suppressed by Rb1 while the high-density lipoprotein (HDL) level was increased. In in vitro assays, Rb1 administration inhibited apoptosis process and the production of pro-inflammation cytokines in AS ECs. The expression levels of GPER, p-PI3K, and p-Akt were upregulated by Rb1, associated with the increased level of Bcl-2 and reduced level of Bax. When the activity of GPER was inhibited by GP-15 in AS ECs, the treatment effect of Rb1 was blocked. However, the activation of PI3K could restore the protective effect of Rb1 after the inhibition of GPER. <strong>CONCLUSIONS</strong> The anti-AS potential of Rb1 was exerted by restoring the regular function of ECs via the activation of GPER-mediated PI3K/Akt signaling.

• Authors: Guoliang Yang, Jun Zhuo, Yuedong Lin, Meng Zhang, Lixin Liu, Xueying Chen, Ronghua Gao
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 25 Pg. 7407-7417 (Oct 03 2019) ISSN: 1643-3750 [Electronic] United States
• PMID: 31609302 (Publication Type: Journal Article)

Chemical References

• Ginsenosides
• Phosphatidylinositols
• Receptors, Estrogen
• Receptors, G-Protein-Coupled
• ginsenoside Rb1
• Proto-Oncogene Proteins c-akt
• G-Protein-Coupled Receptor Kinase 3

Topics

• Animals
• Apoptosis (drug effects)
• Atherosclerosis (drug therapy, physiopathology)
• China
• Diet, High-Fat
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• G-Protein-Coupled Receptor Kinase 3
• Ginsenosides (metabolism, pharmacology)
• Male
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphatidylinositols
• Proto-Oncogene Proteins c-akt (metabolism)
• Rabbits
• Receptors, Estrogen (drug effects, metabolism)
• Receptors, G-Protein-Coupled (drug effects, metabolism)
• Signal Transduction (drug effects)