title: Ginsenoside Re reduces Aβ production by activating PPARγ to inhibit BACE1 in N2a/APP695 cells.
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 Aβ1-40and Aβ1-42. Therefore, ginsenoside Re may be a promising agent for the modulation of Aβ-related pathology in AD.
authors.affiliation: 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.
authors.forename: Guoqiong
authors.initials: G
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Limin
authors.initials: L
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Haijing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Qin
authors.affiliation: 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: zws@bnu.edu.cn.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D036145:Ginsenosides; D047495:PPAR gamma; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C543304:amyloid beta-protein precursor C-terminal fragment beta, human; C049864:ginsenoside Re; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Alzheimer´s disease; Aβ; BACE1; Ginsenoside Re; PPARγ