Metabolomics analysis highlights Yashtimadhu (Glycyrrhiza glabra L.)-mediated neuroprotection in a rotenone-induced cellular model of Parkinson's disease by restoring the mTORC1-AMPK1 axis in autophagic regulation.
complementary and alternative medicine
complex-I inhibition
metabolic stress
multiple reaction monitoring
oxidative stress
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
revised:
14
02
2022
received:
11
09
2021
accepted:
08
03
2022
pubmed:
22
3
2022
medline:
25
5
2022
entrez:
21
3
2022
Statut:
ppublish
Résumé
Parkinson's disease (PD) is an age-associated progressive neurodegenerative movement disorder, and its management strategies are known to cause complications with prolonged usage. We aimed to explore the neuroprotective mechanism of the Indian traditional medicine Yashtimadhu, prepared from the dried roots of Glycyrrhiza glabra L. (licorice) in the rotenone-induced cellular model of PD. Retinoic acid-differentiated IMR-32 cells were treated with rotenone (PD model) and Yashtimadhu extract. Mass spectrometry-based untargeted and targeted metabolomic profiling was carried out to discover altered metabolites. The untargeted metabolomics analysis highlighted the rotenone-induced dysregulation and Yashtimadhu-mediated restoration of metabolites involved in the metabolism of nucleic acids, amino acids, lipids, and citric acid cycle. Targeted validation of citric acid cycle metabolites showed decreased α-ketoglutarate and succinate with rotenone treatment and rescued by Yashtimadhu co-treatment. The dysregulation of the citric acid cycle by rotenone-induced energetic stress via dysregulation of the mTORC1-AMPK1 axis was prevented by Yashtimadhu. Yashtimadhu co-treatment restored rotenone-induced ATG7-dependent autophagy and eventually caspases-mediated cell death. Our analysis links the metabolic alterations modulating energy stress and autophagy, which underlies the Yashtimadhu-mediated neuroprotection in the rotenone-induced cellular model of PD.
Substances chimiques
Neuroprotective Agents
0
Rotenone
03L9OT429T
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2207-2222Subventions
Organisme : Yenepoya (Deemed to be University) Seed Grant
ID : YU/Seed grant/077-2019
Informations de copyright
© 2022 John Wiley & Sons Ltd.
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