Ginsenoside Rg1 Decreases Aβ 1-42 Level by Upregulating PPARγ and IDE Expression in the Hippocampus of a Rat Model of Alzheimer's Disease

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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 (Aβ(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 real-time PCR were used to detect Aβ(1-42), PPARγ, and insulin-degrading enzyme (IDE) expression in the hippocampus. KEY RESULTS: Injection of soluble Aβ(1-42) into the hippocampus led to significant dysfunction of learning and memory, hippocampal histopathological abnormalities and increased Aβ(1-42) levels in the hippocampus. Rg1 treatment significantly improved learning and memory function, attenuated hippocampal histopathological abnormalities, reduced Aβ(1-42) 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 Aβ(1-42), 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.

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Quan, Q. K., Wang, J., Li, X., & Wang, Y. (2013). Ginsenoside Rg1 Decreases Aβ 1-42 Level by Upregulating PPARγ and IDE Expression in the Hippocampus of a Rat Model of Alzheimer’s Disease. PLoS ONE, 8(3). https://doi.org/10.1371/journal.pone.0059155

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