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Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs

Environmental exposure to arsenic has been profoundly associated with chronic systemic disorders, such as neurodegeneration, in both experimental models and clinical studies. The neuronal cells of the brain and the nervous system have a limited regeneration capacity, thus making them more vulnerable...

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Autores principales: Jahan, Sadaf, Ansari, Uzair Ahmad, Siddiqui, Arif Jamal, Iqbal, Danish, Khan, Johra, Banawas, Saeed, Alshehri, Bader, Alshahrani, Mohammed Merae, Alsagaby, Suliman A., Redhu, Neeru Singh, Pant, Aditya Bhushan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147161/
https://www.ncbi.nlm.nih.gov/pubmed/35631419
http://dx.doi.org/10.3390/ph15050593
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author Jahan, Sadaf
Ansari, Uzair Ahmad
Siddiqui, Arif Jamal
Iqbal, Danish
Khan, Johra
Banawas, Saeed
Alshehri, Bader
Alshahrani, Mohammed Merae
Alsagaby, Suliman A.
Redhu, Neeru Singh
Pant, Aditya Bhushan
author_facet Jahan, Sadaf
Ansari, Uzair Ahmad
Siddiqui, Arif Jamal
Iqbal, Danish
Khan, Johra
Banawas, Saeed
Alshehri, Bader
Alshahrani, Mohammed Merae
Alsagaby, Suliman A.
Redhu, Neeru Singh
Pant, Aditya Bhushan
author_sort Jahan, Sadaf
collection PubMed
description Environmental exposure to arsenic has been profoundly associated with chronic systemic disorders, such as neurodegeneration, in both experimental models and clinical studies. The neuronal cells of the brain and the nervous system have a limited regeneration capacity, thus making them more vulnerable to exposure to xenobiotics, leading to long-lasting disabilities. The functional and anatomical complexity of these cells hinders the complete understanding of the mechanisms of neurodegeneration and neuroprotection. The present investigations aimed to evaluate the neuroprotective efficacy of a herbal formulation of Nobiletin (NOB) against the toxic insult induced by sodium arsenate (NA) in human neural progenitor cells (hNPCs) derived from human induced pluripotent stem cells (hiPSCs). Prior to the neuroprotective experiments, biologically safe doses of both NOB and NA were ascertained using standard endpoints of cytotoxicity. Thereafter, the hNPCs were exposed to either NOB (50 μM) or NA (50 μM) and co-exposed to biologically safe concentrations of NA (50 μM) with NOB (50 μM) for a period of up to 48 h. NOB treatment restored the morphological damage (neurite damage), the levels of stress granule G3BP1 (Ras-GTPase-activating protein (SH3 domain)-binding protein) and TIA1 (T cell-restricted intracellular antigen), and the expression of neuronal markers (Tuj1, Nestin, MAP2, and PAX6) when compared to NA-exposed cells. A substantial restoration of reactive oxygen species and mitochondrial membrane potential was also witnessed in the co-exposure group (NA + NOB) in comparison to the NA-exposed group. The findings suggest that NOB possesses a significant restorative/protective potential against the NA challenge in hNPCs under experimental conditions and imply that nobiletin may impart a potential therapeutic impact if studied adequately using in vivo studies.
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spelling pubmed-91471612022-05-29 Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs Jahan, Sadaf Ansari, Uzair Ahmad Siddiqui, Arif Jamal Iqbal, Danish Khan, Johra Banawas, Saeed Alshehri, Bader Alshahrani, Mohammed Merae Alsagaby, Suliman A. Redhu, Neeru Singh Pant, Aditya Bhushan Pharmaceuticals (Basel) Article Environmental exposure to arsenic has been profoundly associated with chronic systemic disorders, such as neurodegeneration, in both experimental models and clinical studies. The neuronal cells of the brain and the nervous system have a limited regeneration capacity, thus making them more vulnerable to exposure to xenobiotics, leading to long-lasting disabilities. The functional and anatomical complexity of these cells hinders the complete understanding of the mechanisms of neurodegeneration and neuroprotection. The present investigations aimed to evaluate the neuroprotective efficacy of a herbal formulation of Nobiletin (NOB) against the toxic insult induced by sodium arsenate (NA) in human neural progenitor cells (hNPCs) derived from human induced pluripotent stem cells (hiPSCs). Prior to the neuroprotective experiments, biologically safe doses of both NOB and NA were ascertained using standard endpoints of cytotoxicity. Thereafter, the hNPCs were exposed to either NOB (50 μM) or NA (50 μM) and co-exposed to biologically safe concentrations of NA (50 μM) with NOB (50 μM) for a period of up to 48 h. NOB treatment restored the morphological damage (neurite damage), the levels of stress granule G3BP1 (Ras-GTPase-activating protein (SH3 domain)-binding protein) and TIA1 (T cell-restricted intracellular antigen), and the expression of neuronal markers (Tuj1, Nestin, MAP2, and PAX6) when compared to NA-exposed cells. A substantial restoration of reactive oxygen species and mitochondrial membrane potential was also witnessed in the co-exposure group (NA + NOB) in comparison to the NA-exposed group. The findings suggest that NOB possesses a significant restorative/protective potential against the NA challenge in hNPCs under experimental conditions and imply that nobiletin may impart a potential therapeutic impact if studied adequately using in vivo studies. MDPI 2022-05-12 /pmc/articles/PMC9147161/ /pubmed/35631419 http://dx.doi.org/10.3390/ph15050593 Text en © 2022 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
Jahan, Sadaf
Ansari, Uzair Ahmad
Siddiqui, Arif Jamal
Iqbal, Danish
Khan, Johra
Banawas, Saeed
Alshehri, Bader
Alshahrani, Mohammed Merae
Alsagaby, Suliman A.
Redhu, Neeru Singh
Pant, Aditya Bhushan
Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs
title Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs
title_full Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs
title_fullStr Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs
title_full_unstemmed Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs
title_short Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs
title_sort nobiletin ameliorates cellular damage and stress response and restores neuronal identity altered by sodium arsenate exposure in human ipscs-derived hnpcs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147161/
https://www.ncbi.nlm.nih.gov/pubmed/35631419
http://dx.doi.org/10.3390/ph15050593
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