Moringa oleifera Modulates MPTP-induced Mitochondrial Dysfunction in Parkinson’s Mouse Model: An in silico and in vivo Analysis
Smriti Singh1, Priyanka Kumari Keshri2, Vijaya Nath Mishra3, Surya Pratap Singh2★★ Corresponding author
- 1Interdisciplinary School of Life Sciences, Institute of Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
- 2Department of Biochemistry, Institute of Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
- 3Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
CORRESPONDENCE
Surya Pratap Singh
Department of Biochemistry, Institute of Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.
Received: 29-09-2023; Accepted: 02-11-2023.
Volume 14, Issue 3 · pp. 187–200 · PUBLISHED 2023 · DOI: 10.1177/0976500X231220085
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ABSTRACT
Background: Parkinson’s disease (PD) is a movement-affecting neurodegenerative condition with an unclear etiology. Recent research suggests targeting poly-(adenosine 5-diphosphate-ribose) polymerase 1 (PARP1) as a potential therapeutic approach for PD treatment. Purpose: The purpose of this study is to assess the effect of an ethanolic extract of Moringa oleifera leaves (MOE) on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian mouse model, with a specific focus on investigating its potential to mitigate the effects of α-synuclein toxicity, oxidative stress–induced hyper-activation of PARP1, and mitochondrial dysfunction associated with PD pathology. Additionally, this study also intends to investigate the alterations in neurobehavioral and biochemical parameters associated with PD pathology. Materials and Methods: An in silico docking study was conducted to investigate the phytochemicals found in M. oleifera (MO, drumstick plant) leaves as the potent inhibitors of PARP1. An in vivo (neurobehavioral, biochemical, and western blot) study was conducted to assess the neuroprotective effect of MOE on the MPTP-induced Parkinsonian mouse model. Results: The results of in silico study showed that the phytochemicals found in MO leaves could be a potent inhibitor of PAPR1. The in vivo study results showed that MOE significantly ameliorated MPTP-induced neurobehavioral and biochemical deficits. MPTP-induced mitochondrial enzyme-complex deficits were found to be restored in MOE-treated mice. Additionally, the result obtained in the western blot analysis showed that MOE significantly restored the levels of tyrosine hydroxylase in MPTP-intoxicated mice. MOE enhanced the expression of the anti-apoptotic factor (Bcl-2) and suppressed the expression of pro-apoptotic factors (Bax and caspase-3). Additionally, the enhanced levels of α-synuclein and PARP1 were significantly suppressed by MOE. Conclusion: Our findings suggest that MOE may possess pharmacological properties that inhibit neuronal damage in MPTP- intoxicated mice. Thus, MOE could be used as a therapeutic agent that can protect dopaminergic neurons from PARP1- induced neuronal damage.
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Singh, S., Keshri, P. K., Mishra, V. N., & Singh, S. P. (2023). Moringa oleifera Modulates MPTP-induced Mitochondrial Dysfunction in Parkinson’s Mouse Model: An in silico and in vivo Analysis. Journal of Pharmacology and Pharmacotherapeutics, 14(3), 187–200. https://doi.org/10.1177/0976500X231220085