The protective effect of parthenolide in an in vitro model of Parkinson's disease through its regulation of nuclear factor-kappa B and oxidative stress.
Oxidative Stress
/ drug effects
Humans
Sesquiterpenes
/ pharmacology
NF-kappa B
/ metabolism
Parkinson Disease
/ metabolism
Reactive Oxygen Species
/ metabolism
Cell Line, Tumor
Cell Survival
/ drug effects
Apoptosis
/ drug effects
Oxidopamine
/ pharmacology
Neuroprotective Agents
/ pharmacology
Antioxidants
/ pharmacology
6-Hydroxydopamine
Neuroprotection
Oxidative stress
Parkinson's disease
Parthenolide
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
17 Jul 2024
17 Jul 2024
Historique:
received:
20
05
2024
accepted:
04
07
2024
medline:
17
7
2024
pubmed:
17
7
2024
entrez:
17
7
2024
Statut:
epublish
Résumé
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, and is due to the degeneration of dopaminergic neurons. It is multifactorial, caused by genetic and environmental factors and currently has no definitive cure. We have investigated the protective effects of parthenolide (PTN), a compound with known anti-inflammatory and antioxidant properties, in an in vitro model of PD, that is induced by 6-OHDA, and that causes neurotoxicity in SH-SY5Y human neuroblastoma cells. SH-SY5Y cells were pretreated with PTN to assess its protective effects in 6-OHDA-induced cellular damage. Cell viability was measured using Alamar blue. Apoptosis was evaluated using an Annexin V-FITC/PI kit. Reactive oxygen species (ROS) levels were quantified, and expression levels of apoptotic markers (Bax, Bcl-2, p53) and NF-κB were analyzed via Western blotting and Quantitative real-time- (qRT-) PCR. We found that 6-OHDA reduced cell viability, that was inhibited significantly by pre-treatment with PTN (p < 0.05). Flow cytometry revealed that PTN reduced apoptosis induced by 6-OHDA. PTN also reduced the ROS levels raised by 6-OHDA (p < 0.05). Moreover, PTN decreased the expression of Bax, p53, NF-κB, and p-NF-κB that were increased by treatment with 6-OHDA. These findings indicate the potential beneficial effects of PTN in an in vitro model of PD via mitigating oxidative stress and inflammation, suggested PTN as a promising agent to be used for PD therapy, warranting further investigation in preclinical and clinical studies.
Sections du résumé
BACKGROUND
BACKGROUND
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, and is due to the degeneration of dopaminergic neurons. It is multifactorial, caused by genetic and environmental factors and currently has no definitive cure. We have investigated the protective effects of parthenolide (PTN), a compound with known anti-inflammatory and antioxidant properties, in an in vitro model of PD, that is induced by 6-OHDA, and that causes neurotoxicity in SH-SY5Y human neuroblastoma cells.
METHODS AND RESULTS
RESULTS
SH-SY5Y cells were pretreated with PTN to assess its protective effects in 6-OHDA-induced cellular damage. Cell viability was measured using Alamar blue. Apoptosis was evaluated using an Annexin V-FITC/PI kit. Reactive oxygen species (ROS) levels were quantified, and expression levels of apoptotic markers (Bax, Bcl-2, p53) and NF-κB were analyzed via Western blotting and Quantitative real-time- (qRT-) PCR. We found that 6-OHDA reduced cell viability, that was inhibited significantly by pre-treatment with PTN (p < 0.05). Flow cytometry revealed that PTN reduced apoptosis induced by 6-OHDA. PTN also reduced the ROS levels raised by 6-OHDA (p < 0.05). Moreover, PTN decreased the expression of Bax, p53, NF-κB, and p-NF-κB that were increased by treatment with 6-OHDA.
CONCLUSION
CONCLUSIONS
These findings indicate the potential beneficial effects of PTN in an in vitro model of PD via mitigating oxidative stress and inflammation, suggested PTN as a promising agent to be used for PD therapy, warranting further investigation in preclinical and clinical studies.
Identifiants
pubmed: 39017801
doi: 10.1007/s11033-024-09779-w
pii: 10.1007/s11033-024-09779-w
doi:
Substances chimiques
parthenolide
2RDB26I5ZB
Sesquiterpenes
0
NF-kappa B
0
Reactive Oxygen Species
0
Oxidopamine
8HW4YBZ748
Neuroprotective Agents
0
Antioxidants
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
819Subventions
Organisme : Mashhad University of M
ID : 4020025
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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