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

Background and Purpose: The present study was designed to examine the effects of ginsenoside Rg1 on expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) and insulin-degrading enzyme (IDE) in the hippocampus of rat model of Alzheimer's disease (AD) to determine how ginsenoside Rg1 (Rg1) decreases A beta levels in AD. Experimental Approach: Experimental AD was induced in rats by a bilateral injection of 10 mg soluble beta-amyloid peptide 1-42 (A beta(1-42)) 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 realtime PCR were used to detect A beta(1-42), PPAR gamma, and insulin-degrading enzyme (IDE) expression in the hippocampus. Key Results: Injection of soluble A beta(1-42) into the hippocampus led to significant dysfunction of learning and memory, hippocampal histopathological abnormalities and increased A beta(1-42) levels in the hippocampus. Rg1 treatment significantly improved learning and memory function, attenuated hippocampal histopathological abnormalities, reduced A beta(1-42) levels and increased PPAR gamma and IDE expression in the hippocampus; these effects of Rg1 could be effectively inhibited by GW9662, a PPAR gamma antagonist. Conclusions and Implications: Given that PPAR gamma can upregulate IDE expression and IDE can degrade A beta(1-42), these results indicate that Rg1 can increase IDE expression in the hippocampus by upregulating PPAR gamma, leading to decreased A beta levels, attenuated hippocampal histopathological abnormalities and improved learning and memory in a rat model of AD.