2. Academic Validation
  3. Involvement of peroxisome proliferator-activated receptor γ in anticonvulsant activity of α-asaronol against pentylenetetrazole-induced seizures in zebrafish

Involvement of peroxisome proliferator-activated receptor γ in anticonvulsant activity of α-asaronol against pentylenetetrazole-induced seizures in zebrafish

  • Neuropharmacology. 2020 Jan 1;162:107760. doi: 10.1016/j.neuropharm.2019.107760.
Meng Jin 1,  Baoyue Zhang 2,  Ying Sun 3,  Shanshan Zhang 2,  Xiang Li 4,  Attila Sik 5,  Yajun Bai 6,  Xiaohui Zheng 7,  Kechun Liu 8
Affiliations

Affiliations

  • 1 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789, East Jingshi Road, Ji'nan, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Biosensor of Shandong Province, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: [email protected].
  • 2 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789, East Jingshi Road, Ji'nan, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Biosensor of Shandong Province, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China.
  • 3 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, 710069, Shanxi Province, PR China; Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shanxi Province, 710069, PR China.
  • 4 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, NO.44 West Culture Road, Ji'nan, 250012, Shandong Province, PR China.
  • 5 Institute of Physiology, Medical School, University of Pecs, Pecs, H-7624, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, H-7624, Hungary; Institute of Clinical Sciences, Medical School, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
  • 6 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, 710069, Shanxi Province, PR China; Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shanxi Province, 710069, PR China. Electronic address: [email protected].
  • 7 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, 710069, Shanxi Province, PR China; Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shanxi Province, 710069, PR China. Electronic address: [email protected].
  • 8 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789, East Jingshi Road, Ji'nan, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Biosensor of Shandong Province, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: [email protected].
PMID: 31493468 DOI: 10.1016/j.neuropharm.2019.107760
Abstract

In mammals, peroxisome proliferators activated receptors (PPARs), the nuclear hormone receptors, have been reported to be involved in seizure control. Selective agonists and antagonists of PPARs raise seizure thresholds and suppress seizures, respectively. In this study, we evaluated the anticonvulsant effects of α-asaronol, a metabolic product of α-asarone, on pentylenetetrazole (PTZ)-induced seizures in zebrafish and investigated the underlying mechanisms. As a result, α-asaronol ameliorated seizures with increase of seizure latency, as well as decrease of seizure-like behavior, c-fos expression, and abnormal neuronal discharge in a concentration dependent manner. By comparing gene expression profiles of zebrafish undergoing seizures and α-asaronol pretreated zebrafish, we found that α-asaronol attenuate seizures through increase of PPAR γ expression, while PPAR γ antagonist GW9662 inhibit the anti-seizures actions of α-asaronol. Moreover, molecular docking simulation implied the physical interaction between α-asaronol and PPAR γ. The overall results indicated that the anticonvulsant effects of α-asaronol are regulated through PPAR γ-mediated pathway, which shed LIGHT on development of α-asaronol as a potential antiepileptic drug. In addition, it is for first time to report that PPAR γ is associated with seizures in zebrafish, supporting previous evidence that zebrafish is a suitable alternative for studying seizures.

Keywords

GW9662; PPAR γ; Seizures; Zebrafish; α-asaronol.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.87%, PPARγ Antagonist