title: 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.
abstract: 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.
authors.affiliation: Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, 50250, Beit Dagan, Israel. aelmann@volcani.agri.gov.il.
authors.forename: Anat
authors.initials: A
authors.lastname: Elmann
authors.affiliation: Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, 50250, Beit Dagan, Israel.
authors.forename: Alona
authors.initials: A
authors.lastname: Telerman
authors.affiliation: Dead Sea & Arava Science Center, Central Arava Branch, Merkaz Sapir, 8682500, Israel.
authors.forename: Rivka
authors.initials: R
authors.lastname: Ofir
authors.affiliation: Raymond and Beverly Sackler Faculty of Exact Sciences, School of Chemistry, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kashman
mesh_terms: D031162:Achillea / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000626425:3,5,4'-trihydroxy-6,7,3'-trimethoxyflavone; D000975:Antioxidants; D005419:Flavonoids; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C000626424:achillolide A; D018698:Glutamic Acid
keywords: 3,5,4′-Trihydroxy-6,7,3′-trimethoxyflavone; Achillolide A; Flavonoids; Glutamate toxicity; Mouse neuroblastoma N2a cells; Sesquiterpene lactones