PMID- 35696798
OWN - NLM
STAT- MEDLINE
DCOM- 20220623
LR  - 20220624
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 103
DP  - 2022 Aug
TI  - Autophagy activation by Terminalia chebula Retz. reduce Abeta generation by shifting 
      APP processing toward non-amyloidogenic pathway in APPswe transgenic SH-SY5Y 
      cells.
PG  - 154245
LID - S0944-7113(22)00324-5 [pii]
LID - 10.1016/j.phymed.2022.154245 [doi]
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative 
      disease. Deposition of amyloid beta plaques (Abeta) is a central hallmark of AD. 
      Accumulating evidence suggest that shifting amyloid precursor protein (APP) 
      metabolism pathway to non-amyloidogenic ways and inducing autophagy play key 
      roles in AD pathology. In published reports, there is no research on the APP 
      metabolic process of Terminalia chebula Retz. (T. Chebula). PURPOSE: The study 
      aims to assess the effects of T. Chebula in AD transgenic SH-SY5Y cells to 
      determine its underlying mechanisms on reducing Abeta level by regulating APP 
      metabolic process. METHODS: The effects of T. Chebula water extract (TWE) on 
      APPswe transgenic SH-SY5Y cells were analyzed by cell viability. ELISA used to 
      quantify extracellular Abeta(1-40) and Abeta(1-42) generations. Western blot and RT-PCR 
      assays were chosen to detect the expression of proteins and genes. The acridine 
      orange (AO) stain was used to label autophagic-vesicles. RESULTS: Treatment with 
      TWE significantly suppressed the Abeta(1-40) and Abeta(1-42) generations of APPswe 
      transgenic cells. TWE inhibited amyloidogenic pathway by reducing BACE1 
      expression, and promote non-amyloidogenic pathway by inducing ADAM10 level of APP 
      metabolism. Additionally, TWE induced autophagy in APPswe transgenic cells 
      involved in APP metabolism to shift the balance to non-amyloidogenic pathway. 
      CONCLUSION: In summary, our finding first time expounded that TWE can inhibit the 
      generation of Abeta(1-40) and Abeta(1-42) in APPswe transgenic SH-SY5Y cells, which 
      were regulated APP metabolism tends to non-amyloid metabolism pathway and 
      mediated by autophagy. The results presented a novel finding for AD treatment of 
      traditional natural medicines.
CI  - Copyright (c) 2022 Elsevier GmbH. All rights reserved.
FAU - Zhao, Longhe
AU  - Zhao L
AD  - School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China.
FAU - Yue, Zhaorong
AU  - Yue Z
AD  - School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China.
FAU - Wang, Yanni
AU  - Wang Y
AD  - School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China.
FAU - Wang, Jiatao
AU  - Wang J
AD  - School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China.
FAU - Ullah, Inam
AU  - Ullah I
AD  - Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui 
      Road No. 222, Lanzhou, China.
FAU - Muhammad, Fahim
AU  - Muhammad F
AD  - Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui 
      Road No. 222, Lanzhou, China.
FAU - Zhou, Yongtao
AU  - Zhou Y
AD  - Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 
      China.
FAU - Zhu, Hongmei
AU  - Zhu H
AD  - School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China.
FAU - Wang, Xin
AU  - Wang X
AD  - School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China. 
      Electronic address: wx@lzu.edu.cn.
FAU - Li, Hongyu
AU  - Li H
AD  - School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, China; 
      Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui 
      Road No. 222, Lanzhou, China. Electronic address: lihy@lzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220606
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
SB  - IM
MH  - *Alzheimer Disease/metabolism
MH  - Amyloid Precursor Protein Secretases/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Aspartic Acid Endopeptidases/genetics
MH  - Autophagy
MH  - Humans
MH  - *Neuroblastoma/drug therapy/metabolism
MH  - *Neurodegenerative Diseases
MH  - *Terminalia
OTO - NOTNLM
OT  - ADAM10
OT  - Autophagy
OT  - Abeta
OT  - BACE1
OT  - Non-amyloidogenic pathway
OT  - Terminalia chebula Retz.
EDAT- 2022/06/14 06:00
MHDA- 2022/06/24 06:00
CRDT- 2022/06/13 18:16
PHST- 2021/10/18 00:00 [received]
PHST- 2022/05/18 00:00 [revised]
PHST- 2022/06/05 00:00 [accepted]
PHST- 2022/06/14 06:00 [pubmed]
PHST- 2022/06/24 06:00 [medline]
PHST- 2022/06/13 18:16 [entrez]
AID - S0944-7113(22)00324-5 [pii]
AID - 10.1016/j.phymed.2022.154245 [doi]
PST - ppublish
SO  - Phytomedicine. 2022 Aug;103:154245. doi: 10.1016/j.phymed.2022.154245. Epub 2022 
      Jun 6.