Neurochemical Research

, Volume 43, Issue 12, pp 2435–2445 | Cite as

Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury

  • Man Zhang
  • Li-Li Huang
  • Chen-Huai Teng
  • Fang-Fang Wu
  • Li-yun Ge
  • Yu-Juan Shi
  • Zheng-Le He
  • Lei Liu
  • Cheng-Jie Jiang
  • Ruo-Nan Hou
  • Jian Xiao
  • Hong-Yu ZhangEmail author
  • Da-Qing ChenEmail author
Original Paper


Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2−/− mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2−/− mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.


TBI Nrf2/ARE Isoliquiritigenin OGD Nrf2−/− 



Funding was provided by the National Natural Science Foundation of China (81472165, 81772450, 81572237, 81501953), The National Science Fund for Outstanding Young Scholars (81722028) and Zhejiang Provincial Natural Science Funding (Q18H150013, LY14D060009).

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Man Zhang
    • 1
  • Li-Li Huang
    • 2
  • Chen-Huai Teng
    • 1
  • Fang-Fang Wu
    • 1
  • Li-yun Ge
    • 2
  • Yu-Juan Shi
    • 3
  • Zheng-Le He
    • 2
  • Lei Liu
    • 1
  • Cheng-Jie Jiang
    • 1
  • Ruo-Nan Hou
    • 1
  • Jian Xiao
    • 2
  • Hong-Yu Zhang
    • 2
    Email author
  • Da-Qing Chen
    • 1
    Email author
  1. 1.Department of Emergency, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou Medical UniversityWenzhouChina
  2. 2.Molecular Pharmacology Research Center, School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhouChina
  3. 3.The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina

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