Affordable Access

deepdyve-link
Publisher Website

Alkaloids extracted from Uncaria rhynchophylla demonstrate neuroprotective effects in MPTP-induced experimental parkinsonism by regulating the PI3K/Akt/mTOR signaling pathway.

Authors
  • Zheng, Meizhu1
  • Chen, Minghui2
  • Liu, Chunming3
  • Fan, Yajun4
  • Shi, Dongfang5
  • 1 The Central Laboratory, Changchun Normal University, Changchun, Jilin, China. Electronic address: [email protected] , (China)
  • 2 College of Life Science, Changchun Normal University, Changchun, Jilin, China. Electronic address: [email protected] , (China)
  • 3 The Central Laboratory, Changchun Normal University, Changchun, Jilin, China. Electronic address: [email protected] , (China)
  • 4 College of Life Science, Changchun Normal University, Changchun, Jilin, China. Electronic address: [email protected] , (China)
  • 5 The Central Laboratory, Changchun Normal University, Changchun, Jilin, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Journal of ethnopharmacology
Publication Date
Feb 10, 2021
Volume
266
Pages
113451–113451
Identifiers
DOI: 10.1016/j.jep.2020.113451
PMID: 33049346
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Alkaloids isolated from Uncaria rhynchophylla (Miq.) Miq. ex Havil. (Rubiaceae), alkaloids (URA) have been used to treat diseases related to the central nervous system, such as Parkinson's disease. Nevertheless, the potential mechanisms underlying their neuroprotective effects are not well-understood. We investigated the neuroprotective effects of URAs in a mouse model of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) and the possible involvement of a molecular signaling pathway. Two typical experiments for animal behavior despair, the spontaneous motor activity and the rotarod experiments, were employed to evaluate the efficacy of URAs in mice with PD symptoms. Dopamine (DA) neurons and their metabolism were evaluated using high-performance liquid chromatography-tandem mass spectrometry. The mechanism of action of the alkaloids was investigated by analyzing their effects on the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway using western blotting. URA treatment effectively improved the behaviors of the mice during the "spontaneous motor activity and latency to fall off the rotarod test". Moreover, URAs demonstrated a protective role in dopaminergic neurons by increasing the expression of the dopamine transporter and tyrosine hydroxylase, which were supposed to be reduced by MPTP, inhibiting dopamine turnover, and changing dopamine and relevant metabolites. In addition to its association with the increase in the Bcl-2/Bad ratio, URA treatment also attenuated the cleaved caspase-3 level and enhanced the phosphorylation of Akt and mTOR. These findings provide evidence that URA can effectively protect neurons from the neurotoxicity caused by MPTP in mouse models of PD by up-regulating the PI3K/Akt/mTOR signaling pathway. Copyright © 2020 Elsevier B.V. All rights reserved.

Report this publication

Statistics

Seen <100 times