, Volume 27, Issue 6, pp 1143–1153 | Cite as

Neuroprotective and anti-inflammatory effects of isoliquiritigenin in kainic acid-induced epileptic rats via the TLR4/MYD88 signaling pathway

  • Xiaobo Zhu
  • Jiankun Liu
  • Ou Chen
  • Jiang Xue
  • Shanying Huang
  • Weiwei ZhuEmail author
  • Yibiao WangEmail author
Original Article


Epileptogenesis is a complex pathological process that occurs after an initial brain injury and involves a series of molecular events. Isoliquiritigenin (ISL), a flavonoid in licorice, is reported to have anti-inflammatory and antioxidant effects in various experimental models, but its specific roles and molecular mechanisms in the epileptogenic process following kainic acid (KA) treatment remain unclear. The purpose of this study was to explore the effects of ISL pretreatment in KA-induced epileptic rats and the underlying mechanisms. Our findings show that ISL pretreatment significantly attenuated the KA-induced expression of ionized calcium‐binding adapter molecule 1 (IBα1)-labeled microglia (F(3, 20) = 97.29, p < 0.01, ηp2 = 0.94) and glial fibrillary acidic protein (GFAP)-positive astrocytes (F(3, 20) = 72.48, p < 0.01, ηp2 = 0.92), and the release of inflammatory mediators, such as TNF-α (F(3, 20) = 133.14, p < 0.01, ηp2 = 0.95), IL-1β, and C–C motif chemokine ligand 3 (CCL3). ISL pretreatment given before KA also significantly prevented apoptotic neuronal injury by upregulating the activities of superoxide dismutase and glutathione peroxidase. It also significantly suppressed the protein levels of Toll-like receptor 4 (TLR4) (F(3, 20) = 63.23, p < 0.01, ηp2 = 0.91) and its downstream molecules, myeloid differentiation primary response 88 (MYD88), phosphorylated (p-)IκBα, and p-NF-κB. Blocking TLR4/MYD88 signaling also attenuated KA-induced neuroinflammation and neuronal damage in the hippocampus. Overall, our study demonstrates that ISL pretreatment plays neuroprotective and anti-inflammatory roles in KA-induced epileptogenesis, which may be mediated by the TLR4/MYD88 signaling pathway.


Isoliquiritigenin Neuroprotection Toll-like receptor 4 Kainic acid Epileptogenesis Rat 



This work was funded by the Basic Research for Natural Science Project of Shandong University (No. 2015TS014) and China Scholarship Council (201706225013). We also thank International Science Editing ( for editing this manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PediatricsThe Second Hospital of Shandong UniversityJinanChina
  2. 2.Department of OphthalmologyThe Second People’s Hospital of Jinan CityJinanChina
  3. 3.Nursing SchoolShandong UniversityJinanChina
  4. 4.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public HealthShandong UniversityJinanChina
  5. 5.Department of PediatricsJinan Central Hospital Affiliated To Shandong UniversityJinanChina
  6. 6.Department of PediatricsThe Second Hospital of Shandong UniversityJinanChina

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