Neuroprotection of Andrographolide against Neurotoxin MPP<sup>+</sup>-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities
Issued Date
2023-05-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-85160380161
Pubmed ID
37239873
Journal Title
International Journal of Molecular Sciences
Volume
24
Issue
10
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.24 No.10 (2023)
Suggested Citation
Prasertsuksri P., Kraokaew P., Pranweerapaiboon K., Sobhon P., Chaithirayanon K. Neuroprotection of Andrographolide against Neurotoxin MPP<sup>+</sup>-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities. International Journal of Molecular Sciences Vol.24 No.10 (2023). doi:10.3390/ijms24108528 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82963
Title
Neuroprotection of Andrographolide against Neurotoxin MPP<sup>+</sup>-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities
Author's Affiliation
Other Contributor(s)
Abstract
Parkinson’s disease (PD) is associated with dopaminergic neuron loss and alpha-synuclein aggregation caused by ROS overproduction, leading to mitochondrial dysfunction and autophagy impairment. Recently, andrographolide (Andro) has been extensively studied for various pharmacological properties, such as anti-diabetic, anti-cancer, anti-inflammatory, and anti-atherosclerosis. However, its potential neuroprotective effects on neurotoxin MPP+-induced SH-SY5Y cells, a cellular PD model, remain uninvestigated. In this study, we hypothesized that Andro has neuroprotective effects against MPP+-induced apoptosis, which may be mediated through the clearance of dysfunctional mitochondria by mitophagy and ROS by antioxidant activities. Herein, Andro pretreatment could attenuate MPP+-induced neuronal cell death that was reflected by reducing mitochondrial membrane potential (MMP) depolarization, alpha-synuclein, and pro-apoptotic proteins expressions. Concomitantly, Andro attenuated MPP+-induced oxidative stress through mitophagy, as indicated by increasing colocalization of MitoTracker Red with LC3, upregulations of the PINK1–Parkin pathway, and autophagy-related proteins. On the contrary, Andro-activated autophagy was compromised when pretreated with 3-MA. Furthermore, Andro activated the Nrf2/KEAP1 pathway, leading to increasing genes encoding antioxidant enzymes and activities. This study elucidated that Andro exhibited significant neuroprotective effects against MPP+-induced SH-SY5Y cell death in vitro by enhancing mitophagy and clearance of alpha-synuclein through autophagy, as well as increasing antioxidant capacity. Our results provide evidence that Andro could be considered a potential supplement for PD prevention.