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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
Zhang, Chao1; Li, Chuwen1; Chen, Shenghui1,2; Li, Zhiping3; Jia, Xuejing1; Wang, Kai1; Bao, Jiaolin1; Liang, Yeer1; Wang, Xiaotong1; Chen, Meiwan1; Li, Peng1; Su, Huanxing1; Wan, Jian-Bo1; Lee, Simon Ming Yuen1; Liu, Kechun3; He, Chengwei1
2017-04
Source PublicationREDOX BIOLOGY
ISSN2213-2317
Volume11
Abstract

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.

KeywordBerberine Hormesis Neuroprotection Pc12 Cells Zebrafish
DOI10.1016/j.redox.2016.10.019
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000398212000001
PublisherELSEVIER SCIENCE BV
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:48   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorHe, Chengwei
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
2.Lee's Pharmaceutical (Hong Kong) Ltd., Shatin, Hong Kong 999077, China
3.Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Key Laboratory for Biosensor, Biology Institute of Shandong Academy of Sciences, Jinan 250014, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhang, Chao,Li, Chuwen,Chen, Shenghui,et al. 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[J]. REDOX BIOLOGY,2017,11.
APA Zhang, Chao.,Li, Chuwen.,Chen, Shenghui.,Li, Zhiping.,Jia, Xuejing.,...&He, Chengwei.(2017).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.REDOX BIOLOGY,11.
MLA Zhang, Chao,et al."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".REDOX BIOLOGY 11(2017).
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