Ethanol Extract ofCirsium japonicumvar.ussurienseKitamura 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 NAD(P)H: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.

E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes

“…The human keratinocyte cells (HaCaT) were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA). HaCaT and HaCaT-ARE (stably transfected with 3xARE-luciferase gene) [ 23 ] cells were maintained at 37 °C in a humidified atmosphere of 5% CO 2 /95% air in RPMI1640 supplemented with 10% heat-inactivated FBS and 50 U/mL penicillin/streptomycin mixture (Invitrogen, Carlsbad, CA, USA). MCR was kindly provided by Dr. Heejung Yang of the Kangwon National University.…”

Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice

“…Chinese physicians usually use CH to treat hemorrhage, hypertension, and hepatitis. Recent pharmacological reports indicated that CH exhibits various pharmacological activities such as hemostatic, hepatoprotective, antidiabetic, anti-inflammatory, antibacterial, and sedative activities [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Due to its taxonomy (Asteraceae family) and morphology being similar to Silybum marianum (L.) Gaertn.…”

Hispidulin-7-O-neohesperidoside from Cirsium japonicum var. ussuriense attenuates the production of inflammatory mediators in LPS-induced raw 264.7 cells and HT-29 cells

“…The aerial parts of this plant are used in oriental medicine as a diuretic, tonic, neuralgia stomachic, antiphlogistic, and detoxicant and have demonstrated hepatoprotective, anti-inflammatory, antitumor, antimutagenic, cytotoxic, and antioxidant effects in pharmacologic studies. [ 9 10 12 ] Flavonoids are reported to be major constituents of C. japonicum var. ussuriense .…”

“…ussuriense have reported hepatoprotective, anti-inflammatory, antitumor, antimutagenic, elimination, and antioxidant effects. [ 9 10 11 12 ] Polyacetylene and flavonoid have been reported as major constituents of C. japonicum var. ussuriense .…”