title: Activation of antioxidant response element in mouse primary cortical cultures with sesquiterpene lactones isolated from Tanacetum parthenium.
abstract: Tanacetum parthenium produces biologically active sesquiterpene lactones (SL). Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate a series of genes termed the antioxidant response element (ARE). Activation of Nrf2/ARE may be useful for the treatment of neurodegenerative disease. In this study we isolated 11 SL from T. parthenium with centrifugal partition chromatography and semipreparative HPLC. Compounds were screened in vitro for their ability to activate the ARE on primary mouse cortical cultures as well as for their toxicity towards the cultures. All SL containing the α-methylene-γ-lactone moiety were able to activate the ARE and cause cellular toxicity. The structure-activity relationship among the SL isolated indicates that the guaianolides were more active and when lacking the endoperoxide functionality less toxic then the germacranolides.
authors.affiliation: PRISNA BV, Leiden, The Netherlands. jtfische@gmail.com
authors.forename: Justin T
authors.initials: JT
authors.lastname: Fischedick
authors.forename: Miranda
authors.initials: M
authors.lastname: Standiford
authors.forename: Delinda A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Ric C H
authors.initials: RC
authors.lastname: De Vos
authors.forename: Slađana
authors.initials: S
authors.lastname: Todorović
authors.forename: Tijana
authors.initials: T
authors.lastname: Banjanac
authors.forename: Rob
authors.initials: R
authors.lastname: Verpoorte
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D061251:Primary Cell Culture; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020903:Tanacetum parthenium / Q000737:chemistry*; D018675:Toxicity Tests / Q000379:methods; D015533:Transcriptional Activation
chemical_list: D007783:Lactones; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D045788:Sesquiterpenes, Germacrane; D045789:Sesquiterpenes, Guaiane