Back to Journals » Drug Design, Development and Therapy » Volume 12

3-n-butylphthalide exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke

Authors Chen N, Zhou Z, Li J, Li B, Feng J, He D, Luo Y, Zheng X, Luo J, Zhang J

Received 2 October 2018

Accepted for publication 26 October 2018

Published 14 December 2018 Volume 2018:12 Pages 4261—4271

DOI https://doi.org/10.2147/DDDT.S189472

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Tuo Deng


Ningyuan Chen,1,* Zhibing Zhou,2,* Ji Li,2,* Bocheng Li,2 Jihua Feng,2 Dan He,2 Yifeng Luo,2 Xiaowen Zheng,2 Jiefeng Luo,3 Jianfeng Zhang2

1Department of Pathophysiology, School of Preclinical Medicine, Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, People’s Republic of China

*These authors contributed equally to this work

Purpose: This study examined whether the neuroprotective drug, 3-n-butylphthalide (NBP), which is used to treat ischemic stroke, prevents mitochondrial dysfunction.
Materials and methods:
PC12 neuronal cells were pretreated for 24 hours with NBP (10 µmol/L), then exposed to oxygen and glucose deprivation (OGD) for 8 hours as an in vitro model of ischemic stroke. Indices of anti-oxidative response, mitochondrial function and mitochondrial dynamics were evaluated.
Results: OGD suppressed cell viability, induced apoptosis and increased caspase-3 activity. NBP significantly reversed these effects. NBP prevented oxidative damage by increasing the activity of superoxide dismutase and lowering levels of malondialdehyde (MDA) and reactive oxygen species (ROS). At the same time, it increased expression of Nrf2, HO-1 and AMPK. NBP attenuated mitochondrial dysfunction by enhancing mitochondrial membrane potential and increasing the activity of mitochondrial respiratory chain complexes I–IV and ATPase. NBP altered the balance of proteins regulating mitochondrial fusion and division.
Conclusion:
NBP exerts neuroprotective actions by enhancing anti-oxidation and attenuating mitochondrial dysfunction. Our findings provide insight into how NBP may exert neuroprotective effects in ischemic stroke and raise the possibility that it may function similarly against other neurodegenerative diseases involving mitochondrial dysfunction.

Keywords: ischemic stroke, mitochondrial dysfunction, mitochondrial dynamics, neuroprotective

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]