Ginsenoside Re reduces Aβ production by activating PPARγ to inhibit BACE1 in N2a/APP695 cells

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• 作者：Guoqiong Cao^a ; ^b ; ^c ; Ping Su^a ; ^b ; ^c ; Shuai Zhang^a ; ^b ; ^c ; Limin Guo^a ; ^b ; ^c ; Haijing Zhang^a ; ^b ; ^c ; Yuexia Liang^a ; ^b ; ^c ; Chunxia Qin^a ; ^b ; ^c ; Wensheng Zhang^a ; ^b ; ^c ; ^d ; ^{zws@bnu.edu.cn}
• 关键词：Ginsenoside Re ; Alzheimer´ ; s disease ; Aβ ; BACE1 ; PPARγ
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 December 2016
• 年：2016
• 卷：793
• 期：Complete
• 页码：101-108
• 全文大小：1369 K
• 卷排序：793

文摘

Alzheimer's disease (AD) is a neurodegenerative disease characterized by β-amyloid protein (Aβ) deposition. Reducing the Aβ load may be a new perspective for AD treatment. Ginsenoside Re is an extract from Panax notoginseng, which is a well-known traditional Chinese medicine that has been used for the treatment of various diseases for years. Ginsenoside Re has been reported to decrease Aβ in Alzheimer's disease animal models, but the mechanism has not been fully elucidated. In the present study, we investigated the mechanism of ginsenoside Re. Our results showed that ginsenoside Re decreased the Aβ levels in N2a/APP695 cells. Aβ peptides are generated by β-secretase (β-site amyloid precursor protein cleaving enzyme 1 (BACE1)) and γ-secretase. We found that ginsenoside Re decreased the BACE1 mRNA and protein levels and inhibited BACE1 activity in the N2a/APP695 cells. Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor that regulates the activity of the BACE1 promoter, and activating PPARγ can inhibit BACE1. The results also showed that ginsenoside Re significantly increased the PPARγ protein and mRNA levels. These effects of ginsenoside Re on BACE1 could be effectively inhibited by the PPARγ antagonist GW9662. These findings indicate that ginsenoside Re inhibits BACE1 through activation of PPARγ, which ultimately reduces the generation of Aβ1–40 and Aβ1–42. Therefore, ginsenoside Re may be a promising agent for the modulation of Aβ-related pathology in AD.