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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00638

Baicalein exerts neuroprotective effects in FeCl3-induced post-traumatic epileptic seizures via suppressing ferroptosis

Qin Li1, Qiu-Qi Li1, Ji-Ning Jia1, Qian-Yi Sun1, Hong-Hao Zhou1, Wei-Lin Jin2* and  Xiao-Yuan Mao1, 3*
  • 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, China
  • 2School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, China
  • 3Xiangya Hospital, Central South University, China

Post-traumatic epilepsy (PTE) is a prevalent type of acquired epilepsy secondary to traumatic brain injury, and is characterized by repeated seizures. Traditional antiepileptic drugs have minimal response in preventing post-traumatic epileptic seizures. It is essential for the development of new therapeutic strategy. Our previous work disclosed a potent neuroprotective role of baicalein, a flavonoid extracted from Scutellaria baicalensis Georgi, against inherited epilepsy in rats. Whether baicalein has protective potential in post-traumatic epileptic seizures and the possible molecular mechanism remain elusive. Additionally, the brain is vulnerable to lipid peroxidation-induced damage due to high consumption of oxygen and abundant polyunsaturated fatty acids in neuronal membranes. Our present investigation aimed to elucidate whether baicalein exerts neuroprotective effects on post-traumatic epileptic seizures by inhibiting ferroptosis, a newly discovered lipid peroxidation-dependent cell death modality. We found that baicalein significantly reduced seizure score, number of seizures, and average seizure duration in an iron chloride (FeCl3)-induced PTE mouse model. The neuroprotective effect of baicalein was also validated in a ferric ammonium citrate (FAC)-induced HT22 hippocampal neuron damage model. Moreover, in vitro, baicalein could remarkably decrease ferroptotic indices (lipid reactive oxygen species, 4-hydroxynonenal, and prostaglandin endoperoxide synthase 2) and inhibit the expression of 12/15-lipoxygenase (12/15-LOX) in an iron-induced HT22 cell damage model. These findings were also validated in a mouse PTE model. It was concluded that baicalein exerted neuroprotective effects against post-traumatic epileptic seizures via suppressing ferroptosis and 12/15-LOX was likely to be involved in baicalein’s neuroprotection.

Keywords: post-traumatic epileptic seizures, Baicalein, 12/15-Lipoxygenase, Lipid Peroxidation, ferroptosis, neuroprotective

Received: 12 Mar 2019; Accepted: 17 May 2019.

Edited by:

Francisco Lopez-Munoz, Universidad Camilo José Cela, Spain

Reviewed by:

Xuemei Qin, Modern Research Center for Traditional Chinese Medicine/PhD
Xingchun Gou, Xi'an Medical University, China  

Copyright: © 2019 Li, Li, Jia, Sun, Zhou, Jin and Mao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Wei-Lin Jin, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China, weilinjin@sjtu.edu.cn
Dr. Xiao-Yuan Mao, Xiangya Hospital, Central South University, Changsha, China, maoxiaoyuan2011@163.com