Ginsenoside Rg1 Decreases Aβ1-42 Level by Upregulating PPARγ and IDE Expression in the Hippocampus of a Rat Model of Alzheimer's Disease

Abstract

Background and Purpose: The present study was designed to examine the effects of ginsenoside Rg1 on expression of peroxisome proliferator-activated receptor γ (PPARγ) and insulin-degrading enzyme (IDE) in the hippocampus of rat model of Alzheimer's disease (AD) to determine how ginsenoside Rg1 (Rg1) decreases Aβ levels in AD. Experimental Approach: Experimental AD was induced in rats by a bilateral injection of 10 μg soluble beta-amyloid peptide 1-42 (Aβ1-42) into the CA1 region of the hippocampus, and the rats were treated with Rg1 (10 mg·kg-1, intraperitoneally) for 28 days. The Morris water maze was used to test spatial learning and memory performance. Hematoxylin-eosin staining was performed to analyze the hippocampal histopathological damage. Immunohistochemistry, western blotting, and real-time PCR were used to detect Aβ1-42, PPARγ, and insulin-degrading enzyme (IDE) expression in the hippocampus. Key Results: Injection of soluble Aβ1-42 into the hippocampus led to significant dysfunction of learning and memory, hippocampal histopathological abnormalities and increased Aβ1-42 levels in the hippocampus. Rg1 treatment significantly improved learning and memory function, attenuated hippocampal histopathological abnormalities, reduced Aβ1-42 levels and increased PPARγ and IDE expression in the hippocampus; these effects of Rg1 could be effectively inhibited by GW9662, a PPARγ antagonist. Conclusions and Implications: Given that PPARγ can upregulate IDE expression and IDE can degrade Aβ1-42, these results indicate that Rg1 can increase IDE expression in the hippocampus by upregulating PPARγ, leading to decreased Aβ levels, attenuated hippocampal histopathological abnormalities and improved learning and memory in a rat model of AD. © 2013 Quan et al.