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Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways

Parkinson’s disease is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and the resultant loss of dopamine in the striatum. Various studies have shown that oxidative stress and neuroinflammation plays a major role in PD progression. In addition, the autophag...

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Autores principales: Jayaraj, Richard L., Beiram, Rami, Azimullah, Sheikh, M. F., Nagoor Meeran, Ojha, Shreesh K., Adem, Abdu, Jalal, Fakhreya Yousuf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348109/
https://www.ncbi.nlm.nih.gov/pubmed/34361780
http://dx.doi.org/10.3390/molecules26154627
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author Jayaraj, Richard L.
Beiram, Rami
Azimullah, Sheikh
M. F., Nagoor Meeran
Ojha, Shreesh K.
Adem, Abdu
Jalal, Fakhreya Yousuf
author_facet Jayaraj, Richard L.
Beiram, Rami
Azimullah, Sheikh
M. F., Nagoor Meeran
Ojha, Shreesh K.
Adem, Abdu
Jalal, Fakhreya Yousuf
author_sort Jayaraj, Richard L.
collection PubMed
description Parkinson’s disease is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and the resultant loss of dopamine in the striatum. Various studies have shown that oxidative stress and neuroinflammation plays a major role in PD progression. In addition, the autophagy lysosome pathway (ALP) plays an important role in the degradation of aggregated proteins, abnormal cytoplasmic organelles and proteins for intracellular homeostasis. Dysfunction of ALP results in the accumulation of α-synuclein and the loss of dopaminergic neurons in PD. Thus, modulating ALP is becoming an appealing therapeutic intervention. In our current study, we wanted to evaluate the neuroprotective potency of noscapine in a rotenone-induced PD rat model. Rats were administered rotenone injections (2.5 mg/kg, i.p.,) daily followed by noscapine (10 mg/kg, i.p.,) for four weeks. Noscapine, an iso-qinulinin alkaloid found naturally in the Papaveraceae family, has traditionally been used in the treatment of cancer, stroke and fibrosis. However, the neuroprotective potency of noscapine has not been analyzed. Our study showed that administration of noscapine decreased the upregulation of pro-inflammatory factors, oxidative stress, and α-synuclein expression with a significant increase in antioxidant enzymes. In addition, noscapine prevented rotenone-induced activation of microglia and astrocytes. These neuroprotective mechanisms resulted in a decrease in dopaminergic neuron loss in SNpc and neuronal fibers in the striatum. Further, noscapine administration enhanced the mTOR-mediated p70S6K pathway as well as inhibited apoptosis. In addition to these mechanisms, noscapine prevented a rotenone-mediated increase in lysosomal degradation, resulting in a decrease in α-synuclein aggregation. However, further studies are needed to further develop noscapine as a potential therapeutic candidate for PD treatment.
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spelling pubmed-83481092021-08-08 Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways Jayaraj, Richard L. Beiram, Rami Azimullah, Sheikh M. F., Nagoor Meeran Ojha, Shreesh K. Adem, Abdu Jalal, Fakhreya Yousuf Molecules Article Parkinson’s disease is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and the resultant loss of dopamine in the striatum. Various studies have shown that oxidative stress and neuroinflammation plays a major role in PD progression. In addition, the autophagy lysosome pathway (ALP) plays an important role in the degradation of aggregated proteins, abnormal cytoplasmic organelles and proteins for intracellular homeostasis. Dysfunction of ALP results in the accumulation of α-synuclein and the loss of dopaminergic neurons in PD. Thus, modulating ALP is becoming an appealing therapeutic intervention. In our current study, we wanted to evaluate the neuroprotective potency of noscapine in a rotenone-induced PD rat model. Rats were administered rotenone injections (2.5 mg/kg, i.p.,) daily followed by noscapine (10 mg/kg, i.p.,) for four weeks. Noscapine, an iso-qinulinin alkaloid found naturally in the Papaveraceae family, has traditionally been used in the treatment of cancer, stroke and fibrosis. However, the neuroprotective potency of noscapine has not been analyzed. Our study showed that administration of noscapine decreased the upregulation of pro-inflammatory factors, oxidative stress, and α-synuclein expression with a significant increase in antioxidant enzymes. In addition, noscapine prevented rotenone-induced activation of microglia and astrocytes. These neuroprotective mechanisms resulted in a decrease in dopaminergic neuron loss in SNpc and neuronal fibers in the striatum. Further, noscapine administration enhanced the mTOR-mediated p70S6K pathway as well as inhibited apoptosis. In addition to these mechanisms, noscapine prevented a rotenone-mediated increase in lysosomal degradation, resulting in a decrease in α-synuclein aggregation. However, further studies are needed to further develop noscapine as a potential therapeutic candidate for PD treatment. MDPI 2021-07-30 /pmc/articles/PMC8348109/ /pubmed/34361780 http://dx.doi.org/10.3390/molecules26154627 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jayaraj, Richard L.
Beiram, Rami
Azimullah, Sheikh
M. F., Nagoor Meeran
Ojha, Shreesh K.
Adem, Abdu
Jalal, Fakhreya Yousuf
Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways
title Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways
title_full Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways
title_fullStr Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways
title_full_unstemmed Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways
title_short Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways
title_sort noscapine prevents rotenone-induced neurotoxicity: involvement of oxidative stress, neuroinflammation and autophagy pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348109/
https://www.ncbi.nlm.nih.gov/pubmed/34361780
http://dx.doi.org/10.3390/molecules26154627
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