Ginsenoside Rg1 Prevents Cognitive Impairment and Hippocampal Neuronal Apoptosis in Experimental Vascular Dementia Mice by Promoting GPR30 Expression.

Fengming Shen,Feng Gao,Guoqi Zhu,Jingji Wang,Juan Wang,Michele Fornaro

doi:10.1155/2021/2412220

Abstract

This study is aimed at investigating the potential roles of G protein-coupled estrogen receptor 1 (GPER, also known as GPR30) in the preventive effect of ginsenoside Rg1 against cognitive impairment and hippocampal cell apoptosis in experimental vascular dementia (VD) in mice. The effects of bilateral common carotid artery stenosis (BCAS) on GPR30 expression at mRNA level were evaluated. Thereafter, the BCAS mouse model was utilized to evaluate the protection of Rg1 (0.1, 1, 10 mg/kg, 14 days, ip). Spatial memory was evaluated by water Morris Maze 7 days post BCAS. After behavioral tests, neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and potential mechanisms were determined using western blotting and quantitative real-time PCR. Our results showed that GPR30 expression in the hippocampal region at mRNA level was promoted 30 min, 3 h, 6 h, and 24 h following BCAS. Ginsenoside Rg1 (1 or 10 mg/kg, 14 days, ip) promoted GPR30 expression in the hippocampus of model mice (after behavioral tests) but did not alter GPR30 expression in the hippocampus of control mice. Moreover, treatment of ginsenoside Rg1 (10 mg/kg) or G1 (5 μg/kg), a GPR30 agonist, prevented BCAS-induced memory impairment and hippocampal neuronal loss and apoptosis and promoted the ratio of Bcl-2 to Bax expression in the hippocampus (after behavioral tests). On the contrary, G15 (185 μg/kg), an antagonist of GPR30, aggravated BCAS-induced hippocampal neuronal loss and apoptosis. Finally, drug-target molecular docking pointed that Rg1 had a lower binding energy with GPR30 compared with Bax and Bcl-2. Together, our data implicate that ginsenoside Rg1 prevents cognitive impairment and hippocampal neuronal apoptosis in VD mice, likely through promoting GPR30 expression. These results would provide important implications for the application of Rg1 in the treatment of VD.

Highlights

Vascular dementia (VD) is a type of cognitive impairment syndrome caused by cerebral hypoperfusion or ischemic cerebrovascular diseases, which involves pathological changes in brain regions such as the hippocampus and cortex [1]
The expression of GPR30 mRNA at 30 min, 3 h, 6 h, and 24 h after bilateral common carotid artery stenosis (BCAS) was detected. 30 min, 3 h, 6 h, and 24 h after establishment of BCAS, GPR30 expression at mRNA level in the hippocampus was higher than that in the sham group (Figure 2, P < 0:05), which suggested that the expression of GPR30 increased after the modeling of BCAS
Compared with the model group, there was no significant difference in the expression of GPR30 in the hippocampus of mice in the low-dose group of Rg1, while the expression of GPR30 at mRNA and protein levels in the hippocampus of high and medium doses of ginsenoside Rg1 groups were upregulated significantly (Figures 3(a) and 3(b), P < 0:05)

Summary

Introduction

Vascular dementia (VD) is a type of cognitive impairment syndrome caused by cerebral hypoperfusion or ischemic cerebrovascular diseases, which involves pathological changes in brain regions such as the hippocampus and cortex [1]. VD patients present with memory impairment, as well as behavioral and psychological symptoms such as anxiety and depression [2]. VD has become the second largest type of dementia threatening elderly people after Alzheimer’s disease, accounting for about 15%-20% of dementia patients [3, 4]. Panax ginseng has been widely used to treat organic and psychosomatic diseases since ancient times [5]. Ginsenosides, especially ginsenoside Rg1, are considered the main active ingredients of ginseng [6].

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