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Baicalin provides neuroprotection in traumatic brain injury mice model through Akt/Nrf2 pathway

Authors Fang J, Wang H, Zhou J, Dai W, Zhu Y, Zhou Y, Wang X, Zhou M

Received 28 January 2018

Accepted for publication 30 May 2018

Published 10 August 2018 Volume 2018:12 Pages 2497—2508

DOI https://doi.org/10.2147/DDDT.S163951

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti


Jiang Fang,1 Handong Wang,1 Jian Zhou,2 Wei Dai,2 Yihao Zhu,3 Yuan Zhou,2 Xiaoliang Wang,3 Mengliang Zhou3

1Department of Neurosurgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China; 2Department of Neurosurgery, Jinling Hospital, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, China; 3Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China

Background: The neuroprotective effects of Baicalin have been confirmed in several central nervous system (CNS) diseases. However, its possible effect on traumatic brain injury (TBI) model is still not clear. The present study is aimed to investigate the role and the underling mechanisms of 7-d-glucuronic acid-5,6-dihydroxyflavone (Baicalin) on TBI model.
Methods: The weight-drop model of TBI in Institute of Cancer Research mice was treated with Baicalin intraperitoneally at 30 minutes after TBI. LY294002 (LY) (a commonly used PI3K/Akt pathway inhibitor) was injected into the left ventricle at 30 minutes before TBI. All mice were euthanized at 24 hours after TBI to collect the brain tissue for a series of tests except for neurological function, which was measured at 2 hours and 1 and 3 days post-TBI.
Results: Baicalin administration significantly improved neurobehavioral function, alleviated brain edema, and reduced apoptosis-positive cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay accompanied with the upregulation of B-cell lymphoma 2 (Bcl-2) and downregulation of Bcl-2-associated X protein (Bax) and cleaved-caspase 3 by Western blot. Besides, TBI-induced oxidant stress status was also restored in the Baicalin group by measuring malondialdehyde (MDA) content, glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels in the injured brain cortex. Furthermore, translocation of Nrf2 to the nucleus was dramatically enhanced by Baicalin verified by immunofluorescence and Western blot analyses. Accordingly, its downstream antioxidative enzymes nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) were also activated by Baicalin confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. However, cotreatment with Baicalin and LY could partly abolish Baicalin-induced activation of Nrf2 and its neuroprotective effects in TBI.
Conclusion: This study demonstrates that Baicalin provides a neuroprotective effect in TBI mice model via activating the Akt/Nrf2 pathway.

Keywords: Baicalin, traumatic brain injury, Akt, nuclear factor erythroid 2-related factor 2, apoptosis, oxidative stress

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