title: Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway.
abstract: Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H(2)O(2) induced cell death.
authors.affiliation: PRISNA BV, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
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: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D027543:Salvia officinalis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004224:Diterpenes; D051267:NF-E2-Related Factor 2; D010636:Phenols; D010936:Plant Extracts; D006861:Hydrogen Peroxide