Mechanistic evaluation of Ursolic acid against rotenone induced Parkinson's disease- emphasizing the role of mitochondrial biogenesis.
Animals
Cyclooxygenase Inhibitors
/ pharmacology
Drug Evaluation, Preclinical
/ methods
Glutathione
/ metabolism
Male
Mitochondria
/ drug effects
Organelle Biogenesis
Oxidative Stress
/ drug effects
Parkinsonian Disorders
/ chemically induced
Rats
Rats, Sprague-Dawley
Rotenone
/ toxicity
Triterpenes
/ pharmacology
Ursolic Acid
Barnes maze test
Mitochondrial biogenesis
MtCO1 (COX1)
Parkinson’s disease
Rotenone
Ursolic acid
Journal
Brain research bulletin
ISSN: 1873-2747
Titre abrégé: Brain Res Bull
Pays: United States
ID NLM: 7605818
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
15
11
2019
revised:
18
02
2020
accepted:
03
03
2020
pubmed:
10
3
2020
medline:
1
9
2021
entrez:
10
3
2020
Statut:
ppublish
Résumé
Parkinson's disease (PD) is an age associated, progressive and a second most common neurodegenerative disease. It is caused due to degeneration of dopaminergic neurons in substantia nigra (SN). Various studies implicate mitochondrial dysfunction, oxidative stress, altered degradation of misfolded proteins in PD pathogenesis. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is reported to possess a number of biological activities viz. anti-oxidant, anti-inflammatory etc. The focus of our study was to assess the neuroprotective potential of UA against the rotenone induced pathophysiological alterations. In this study rats were subjected to stereotaxic bilateral injection of rotenone (12 μg/μl) in SN. Further, they were treated per-orally with UA (5 and 10 mg/kg) for 30 days. During the study, neurobehavioral tests comprising Rota-rod, Open field and Barnes maze (BMT) were conducted. At the end of 30 days, the antioxidant (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammatory (TNF-α) parameters, mitochondrial complex I, mitochondrial biogenesis (MB) and immunohistochemical analysis (TH positive neurons, Glial Fibrillary Acidic Protein (GFAP)) was performed. The results exhibited significant amelioration in the motor deficits by UA which can be attributed to the protection of TH positive neurons from degeneration. A significant improvement in the cognitive function due to UA was observed in BMT. Biochemically, the oxidative stress and inflammation triggered by rotenone was significantly diminished by UA. It also significantly obviated the complex I inhibition and promoted MB. The preliminary results thus firmly advocate the neuroprotective potential of UA to prevent rotenone induced neurotoxicity in rats.
Identifiants
pubmed: 32147532
pii: S0361-9230(19)30913-X
doi: 10.1016/j.brainresbull.2020.03.003
pii:
doi:
Substances chimiques
Cyclooxygenase Inhibitors
0
Triterpenes
0
Rotenone
03L9OT429T
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
150-161Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None