Dehydroglyasperin C isolated from licorice caused Nrf2-mediated induction of detoxifying enzymes.
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.
Seo
Ji Yeon
JY
School of Applied Biosciences, Kyungpook National University, Deagu 702-701, Republic of Korea.
Lee
Yeon Sil
YS
Kim
Hyo Jung
HJ
Lim
Soon Sung
SS
Lim
Ji Sun
JS
Lee
In Ae
IA
Lee
Chung Hwan
CH
Yoon Park
Jung Han
JH
Kim
Jong-Sang
JS
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
D001578:Benzopyrans; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; C548688:dehydroglyasperin C; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase