title: Ethanol Extract of Cirsium japonicum var. ussuriense Kitamura Exhibits the Activation of Nuclear Factor Erythroid 2-Related Factor 2-dependent Antioxidant Response Element and Protects Human Keratinocyte HaCaT Cells Against Oxidative DNA Damage.
abstract: Keratinocytes are constantly exposed to extracellular insults, such as ultraviolet B, toxic chemicals and mechanical stress, all of which can facilitate the aging of keratinocytes via the generation of intracellular reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in protecting keratinocytes against oxidants and xenobiotics by binding to the antioxidant response element (ARE), a cis-acting element existing in the promoter of most phase II cytoprotective genes. In the present study, we have attempted to find novel ethanol extract(s) of indigenous plants of Jeju island, Korea that can activate the Nrf2/ARE-dependent gene expression in human keratinocyte HaCaT cells. As a result, we identified that ethanol extract of Cirsium japonicum var. ussuriense Kitamura (ECJUK) elicited strong stimulatory effect on the ARE-dependent gene expression. Supporting this observation, we found that ECJUK induced the expression of Nrf2, hemoxygenase-1, and
  quinone oxidoreductase-1 and this event was correlated with Akt1 phosphorylation. We also found that ECJUK increased the intracellular reduced glutathione level and suppressed 12-O-tetradecanoylphorbol acetate-induced 8-hydroxyguanosine formation without affecting the overall viability. Collectively, our results provide evidence that ECJUK can protect against oxidative stress-mediated damages through the activation of Nrf2/ARE-dependent phase II cytoprotective gene expression.
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Incheon, Korea.
authors.forename: Ok-Kyung
authors.initials: OK
authors.lastname: Yoo
authors.affiliation: Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju, Incheon, Korea.
authors.forename: Bu Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Natural Product Laboratory, Daebong LS Co., Ltd., Incheon, Korea.
authors.forename: Jin-Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Central Research Institute, UCL Co., Ltd., Incheon, Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Central Research Institute, UCL Co., Ltd., Incheon, Korea.
authors.forename: Byoung-Kwon
authors.initials: BK
authors.lastname: Park
authors.affiliation: Department of Natural Product Laboratory, Daebong LS Co., Ltd., Incheon, Korea.
authors.forename: Chul Gue
authors.initials: CG
authors.lastname: Joo
authors.affiliation: Central Research Institute, UCL Co., Ltd., Incheon, Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Heo
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Incheon, Korea.
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Keum
keywords: Antioxidant response elements; Ethanol extract of Cirsium japonicum var. ussuriense Kitamura; Nuclear factor erythroid 2-related factor 2; Reactive oxygen species