title: Dehydroglyasperin C isolated from licorice caused Nrf2-mediated induction of detoxifying enzymes.
abstract: Our preliminary experiment demonstrated that a n-hexane/EtOH (9:1, volume) extract of Glycyrrhiza uralensis (licorice) caused a significant induction of NAD(P)H:oxidoquinone reductase (NQO1), one of the well-known phase 2 detoxifying enzymes. We isolated dehydroglyasperin C (DGC) as a potent phase 2 enzyme inducer from licorice. DGC induced NQO1 both in wild-type murine hepatoma Hepa1c1c7 and ARNT-lacking BPRc1 cells, indicating that the compound is a monofunctional inducer. The compound induced not only NQO1 but also some other phase 2 detoxifying/antioxidant enzymes, such as glutathione S-transferase, gamma-glutamylcysteine synthase, glutathione reductase, and heme oxygenase 1. Similar to most monofunctional inducers, DGC caused the accumulation of Nrf2 in the nucleus in dose- and time-dependent manners and thereby activated expression of phase 2 detoxifying enzymes. It also resulted in a dose-dependent increase in the luciferase activity in the reporter assay, in which HepG2-C8 cells transfected with antioxidant response element (ARE)-luciferase construct were used, suggesting that the induction of phase 2 detoxifying and antioxidant enzymes could be achieved through the interaction of Nrf2 with the ARE sequence in the promoter region of their genes.
authors.affiliation: School of Applied Biosciences, Kyungpook National University, Deagu 702-701, Republic of Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Seo
authors.forename: Yeon Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Lim
authors.forename: In Ae
authors.initials: IA
authors.lastname: Lee
authors.forename: Chung Hwan
authors.initials: CH
authors.lastname: Lee
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Yoon Park
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D001578:Benzopyrans; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; C548688:dehydroglyasperin C; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase