NDLI: Neuroprotection of Andrographolide against Neurotoxin MPP<sup>+</sup>-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities.

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Neuroprotection of Andrographolide against Neurotoxin MPP⁺-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities.

Content Provider	Europe PMC
Author	Prasertsuksri, Prachayaporn Kraokaew, Pichnaree Pranweerapaiboon, Kanta Sobhon, Prasert Chaithirayanon, Kulathida
Editor	Ricci, Claudia
Copyright Year	2023
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.
Journal	International Journal of Molecular Sciences [Int J Mol Sci]
Volume Number	24
DOI	10.3390/ijms24108528
PubMed Central reference number	PMC10217882
Issue Number	10
PubMed reference number	37239873
e-ISSN	14220067
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2023-05-10
Access Restriction	Open
Subject Keyword	Parkinson’s disease andrographolide MPP+ SH-SY5Y cells ROS Nrf2 mitophagy
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Molecular Biology Spectroscopy Catalysis Computer Science Applications Medicine Inorganic Chemistry Organic Chemistry

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Neuroprotection of Andrographolide against Neurotoxin MPP+-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities.

Neuroprotection of Andrographolide against Neurotoxin MPP⁺-Induced Apoptosis in SH-SY5Y Cells via Activating Mitophagy, Autophagy, and Antioxidant Activities.