title: Induction of antioxidant and phase 2 drug-metabolizing enzymes by falcarindiol isolated from Notopterygium incisum extract, which activates the Nrf2/ARE pathway, leads to cytoprotection against oxidative and electrophilic stress.
abstract: In the present study, we isolated falcarindiol from Notopterygium incisum and investigated the effect of falcarindiol on the expression of antioxidant enzymes (AOEs), such as catalase, and phase 2 drug-metabolizing enzymes (DMEs), such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase 1, in a cultured cell line from normal rat liver, Clone 9 cells. Exposure of Clone 9 cells to falcarindiol resulted in the significant induction of AOEs and phase 2 DMEs. Western blot analysis and transfection studies using a luciferase reporter construct demonstrated that the induction of AOEs and phase 2 DMEs by falcarindiol was caused through the Nrf2/ARE (nuclear factor-E2-related factor 2/antioxidant response element) pathway. Pretreatment of cells with falcarindiol accelerated the detoxification of a potentially toxic quinone (menadione) and mitigated menadione-induced cytotoxicity. We found that falcarindiol was a novel inducer of AOEs and phase 2 DMEs and falcarindiol might exhibit chemopreventive activity.
authors.affiliation: Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji-shi, Tokyo, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohnuma
authors.forename: Takao
authors.initials: T
authors.lastname: Komatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakayama
authors.forename: Takahito
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Ogura
authors.forename: Akira
authors.initials: A
authors.lastname: Hiratsuka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D019661:Apiaceae / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity; D053280:Diynes / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D004583:Electrons; D004790:Enzyme Induction / Q000187:drug effects; D004798:Enzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005233:Fatty Alcohols / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D050217:Metabolic Detoxication, Phase II; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects*; D024483:Vitamin K 3 / Q000378:metabolism / Q000633:toxicity
chemical_list: D000975:Antioxidants; D003603:Cytotoxins; D053280:Diynes; D004798:Enzymes; D005233:Fatty Alcohols; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D012333:RNA, Messenger; C034379:falcarindiol; D024483:Vitamin K 3; D051547:Heme Oxygenase-1