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

被引：168

作者：

Zhang, Chao ^{[1
]}

Li, Chuwen ^{[1
]}

Chen, Shenghui ^{[1
,2
]}

Li, Zhiping ^{[3
]}

Jia, Xuejing ^{[1
]}

Wang, Kai ^{[1
]}

Bao, Jiaolin ^{[1
]}

Liang, Yeer ^{[1
]}

Wang, Xiaotong ^{[1
]}

Chen, Meiwan ^{[1
]}

Li, Peng ^{[1
]}

Su, Huanxing ^{[1
]}

Wan, Jian-Bo ^{[1
]}

Lee, Simon Ming Yuen ^{[1
]}

Liu, Kechun ^{[3
]}

He, Chengwei ^{[1
]}

机构：

[1] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China

[2] Lees Pharmaceut Hong Kong Ltd, Shatin 999077, Hong Kong, Peoples R China

[3] Shandong Acad Sci, Key Lab Drug Screening Technol, Shandong Prov Key Lab Biosensor, Inst Biol, Jinan 250014, Peoples R China

来源：

REDOX BIOLOGY | 2017年 / 11卷

基金：

中国国家自然科学基金;

关键词：

Berberine; Hormesis; Neuroprotection; PC12; cells; Zebrafish; OXIDATIVE STRESS; CELLULAR STRESS; NONTRADITIONAL MODEL; ALZHEIMERS-DISEASE; HORMESIS; PHYTOCHEMICALS; APOPTOSIS; NEURONS; TARGETS; ACTIVATION;

D O I：

10.1016/j.redox.2016.10.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1 / 11

页数：11

共 63 条

[1]

[Anonymous], 2012, EVID BASED COMPLEMEN, DOI DOI 10.1155/2012/429412

[2] Hormesis/preconditioning mechanisms, the nervous system and aging [J].