Journal of Molecular Neuroscience

, Volume 62, Issue 1, pp 99–105 | Cite as

Glutamate Toxicity to Differentiated Neuroblastoma N2a Cells Is Prevented by the Sesquiterpene Lactone Achillolide A and the Flavonoid 3,5,4′-Trihydroxy-6,7,3′-Trimethoxyflavone from Achillea fragrantissima

  • Anat ElmannEmail author
  • Alona Telerman
  • Rivka Ofir
  • Yoel Kashman


Glutamate toxicity is a major contributor to the pathophysiology of numerous neurodegenerative diseases including amyotrophic lateral sclerosis and Alzheimer’s disease. Therefore, protecting neuronal cells against glutamate-induced cytotoxicity might be an effective approach for the treatment of these diseases. We have previously purified from the medicinal plant Achillea fragrantissima two bioactive compounds which were not studied before: the sesquiterpene lactone achillolide A and the flavonoid 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TTF). We have shown that these compounds protect astrocytes from oxidative stress-induced cell death and inhibit microglial activation. The current study examined for the first time their effects on differentiated mouse neuroblastoma N2a cells and on glutamate toxicity. We have found that, although these compounds belong to different chemical families, they protect neuronal cells from glutamate toxicity. We further demonstrate that this protective effect might be, at least partially, due to inhibitory effects of these compounds on the levels of reactive oxygen species produced following treatment with glutamate.


Achillolide A 3,5,4′-Trihydroxy-6,7,3′-trimethoxyflavone Flavonoids Sesquiterpene lactones Mouse neuroblastoma N2a cells Glutamate toxicity 



This research was supported by research grant no. IS-4473-11 from BARD, the US–Israel Binational Agricultural Research and Development Fund. The authors wish to thank Yardena Abudi (TAU), Miriam Rindner (ARO), and Sigrid Penno-Winters (Arava-Dead Sea Science Center) for their technical assistance. This is publication 773/17 from the Agricultural Research Organization.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Anat Elmann
    • 1
    Email author
  • Alona Telerman
    • 1
  • Rivka Ofir
    • 2
  • Yoel Kashman
    • 3
  1. 1.Department of Food Quality and Safety, Volcani CenterAgricultural Research OrganizationBeit DaganIsrael
  2. 2.Dead Sea & Arava Science CenterMerkaz SapirIsrael
  3. 3.Raymond and Beverly Sackler Faculty of Exact Sciences, School of ChemistryTel Aviv UniversityTel AvivIsrael

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