2. Academic Validation
  3. Ginsenoside Re reduces Aβ production by activating PPARγ to inhibit BACE1 in N2a/APP695 cells

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

  • Eur J Pharmacol. 2016 Dec 15;793:101-108. doi: 10.1016/j.ejphar.2016.11.006.
Guoqiong Cao 1,  Ping Su 1,  Shuai Zhang 1,  Limin Guo 1,  Haijing Zhang 1,  Yuexia Liang 1,  Chunxia Qin 1,  Wensheng Zhang 2
Affiliations

Affiliations

  • 1 Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100088, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China.
  • 2 Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100088, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing 100088, China; College of Resources Science Technology, Beijing Normal University, Beijing 100875, China; National & Local United Engineering Research Center for Sanqi Resources Protection and Utilization Technology, Kunming 650000, China. Electronic address: [email protected].
PMID: 27840193 DOI: 10.1016/j.ejphar.2016.11.006
Abstract

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.

Keywords

Alzheimer´s disease; Aβ; BACE1; Ginsenoside Re; PPARγ.

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