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Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways

Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemica...

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Autores principales: Zhang, Chao, Li, Chuwen, Chen, Shenghui, Li, Zhiping, Jia, Xuejing, Wang, Kai, Bao, Jiaolin, Liang, Yeer, Wang, Xiaotong, Chen, Meiwan, Li, Peng, Su, Huanxing, Wan, Jian-Bo, Lee, Simon Ming Yuen, Liu, Kechun, He, Chengwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107737/
https://www.ncbi.nlm.nih.gov/pubmed/27835779
http://dx.doi.org/10.1016/j.redox.2016.10.019
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author Zhang, Chao
Li, Chuwen
Chen, Shenghui
Li, Zhiping
Jia, Xuejing
Wang, Kai
Bao, Jiaolin
Liang, Yeer
Wang, Xiaotong
Chen, Meiwan
Li, Peng
Su, Huanxing
Wan, Jian-Bo
Lee, Simon Ming Yuen
Liu, Kechun
He, Chengwei
author_facet Zhang, Chao
Li, Chuwen
Chen, Shenghui
Li, Zhiping
Jia, Xuejing
Wang, Kai
Bao, Jiaolin
Liang, Yeer
Wang, Xiaotong
Chen, Meiwan
Li, Peng
Su, Huanxing
Wan, Jian-Bo
Lee, Simon Ming Yuen
Liu, Kechun
He, Chengwei
author_sort Zhang, Chao
collection PubMed
description Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways.
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spelling pubmed-51077372016-11-21 Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways Zhang, Chao Li, Chuwen Chen, Shenghui Li, Zhiping Jia, Xuejing Wang, Kai Bao, Jiaolin Liang, Yeer Wang, Xiaotong Chen, Meiwan Li, Peng Su, Huanxing Wan, Jian-Bo Lee, Simon Ming Yuen Liu, Kechun He, Chengwei Redox Biol Research Paper Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways. Elsevier 2016-11-04 /pmc/articles/PMC5107737/ /pubmed/27835779 http://dx.doi.org/10.1016/j.redox.2016.10.019 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Zhang, Chao
Li, Chuwen
Chen, Shenghui
Li, Zhiping
Jia, Xuejing
Wang, Kai
Bao, Jiaolin
Liang, Yeer
Wang, Xiaotong
Chen, Meiwan
Li, Peng
Su, Huanxing
Wan, Jian-Bo
Lee, Simon Ming Yuen
Liu, Kechun
He, Chengwei
Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways
title Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways
title_full Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways
title_fullStr Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways
title_full_unstemmed Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways
title_short Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways
title_sort berberine protects against 6-ohda-induced neurotoxicity in pc12 cells and zebrafish through hormetic mechanisms involving pi3k/akt/bcl-2 and nrf2/ho-1 pathways
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107737/
https://www.ncbi.nlm.nih.gov/pubmed/27835779
http://dx.doi.org/10.1016/j.redox.2016.10.019
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