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Neurochemical Research

, Volume 44, Issue 2, pp 472–484 | Cite as

Aucubin Alleviates Seizures Activity in Li-Pilocarpine-Induced Epileptic Mice: Involvement of Inhibition of Neuroinflammation and Regulation of Neurotransmission

  • Siyu Chen
  • Xiangchang Zeng
  • Wenjing Zong
  • Xintong Wang
  • Lulu Chen
  • Luping Zhou
  • Chaopeng Li
  • Qi Huang
  • Xinyi Huang
  • Guirong Zeng
  • Kai HuEmail author
  • Dong-Sheng OuyangEmail author
Original Paper
  • 118 Downloads

Abstract

Neuroinflammation and imbalance of neurotransmitters play pivotal roles in seizures and epileptogenesis. Aucubin (AU) is an iridoid glycoside derived from Eucommia ulmoides that possesses anti-inflammatory and neuroprotective effects. However, the anti-seizure effects of AU have not been reported so far. The present study was designed to investigate the effects of AU on pilocarpine (PILO) induced seizures and its role in the regulation of neuroinflammation and neurotransmission. We found that AU reduced seizure intensity and prolonged the latency of seizures. AU significantly attenuated the activation of astrocytes and microglia and reduced the levels of interleukine-1 beta (IL-1β), high mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α). Furthermore, the contents of γ-aminobutyric acid (GABA) were increased while the levels of glutamate were decreased in the hippocampus with AU treatment. The expression of γ-aminobutyric acid type A receptor subunit α1 (GABAARα1) and glutamate transporter-1 (GLT-1) protein were up-regulated in AU treatment group. However, AU had no significant effect on N-methyl-d-aspartate receptor subunit 2B (NR2B) expression in status epilepticus (SE). In conclusion, our findings provide the first evidence that AU can exert anti-seizure effects by attenuating gliosis and regulating neurotransmission. The results suggest that AU may be developed as a drug candidate for the treatment of epilepsy.

Keywords

Aucubin Epilepsy Gliosis Neuroinflammation Neurotransmission 

Notes

Acknowledgements

This study was supported by the National Development of Key Novel Drugs for Special Projects of China (Grant No.: 2017ZX09304014), the Natural Science Foundation of Hunan Province (Grant No.: 2016JJ4116) and the Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples (2017TP1037).

Compliance with Ethical Standards

Conflict of interest

None.

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Authors and Affiliations

  1. 1.Department of Clinical Pharmacology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Institute of Clinical Pharmacology, Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Department of Pharmacy, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  4. 4.Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs & Hunan Provincial Research Center for Safety Evaluation of DrugsChangshaPeople’s Republic of China
  5. 5.Hunan Key Laboratory for Bioanalysis of Complex Matrix SamplesChangsha Duxact Biotech Co., LtdChangshaPeople’s Republic of China
  6. 6.Department of Neurology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China

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