title: Brazilian green propolis water extract up-regulates the early expression level of HO-1 and accelerates Nrf2 after UVA irradiation.
abstract: BACKGROUND
  Exposure to ultraviolet A (UVA) irradiation is the major cause of human skin aging. Suppression of UVA irradiation-induced skin fibroblast cell damage protects the skin against aging. An oxidative stress response transcription factor nuclear factor-(erythroid-derived 2)-related factor 2 (Nrf2) has an important role as a cytoprotective system against oxidative stress in the human skin and other organs. Propolis has been commonly used as a traditional medicine since ancient times. The water extract of propolis (WEP) mainly contains caffeoylquinic acids. In our previous study, we reported that WEP and its major constituents protected immortalized human skin fibroblast cells (NB1-RGB) against UVA irradiation-induced cell death. In this study, we examined the mechanism of WEP-mediated skin protection and the possible involvement of Nrf2/antioxidant response element (ARE) pathways.
  
  
  METHODS
  Brazilian green propolis was used in the present study (Minas Gerais State, Brazil), Baccharis dracunculifolia is its main source. The Baccharis propolis was extracted with water at 50 °C to yield water extract. The NB1-RGB cell cultures were incubated for 23 h. After replenishing the medium, WEP or its constituents were added to the cell cultures. After 1 h, the cells were exposed to 10 J/cm(2) of UVA light (365 nm UVA light source, CL-1000 L UV Closslinkers, Ultraviolet Products Ltd., Cambridge, UK). Heme oxygenase-1 (HO-1) expression levels in NB1-RGB cells were evaluated using western blotting. Nrf2 nuclear translocation changes in NB1-RGB cells were indicated using immunostaining.
  
  
  RESULTS
  We demonstrated that WEP pretreatment up-regulated HO-1 expression level after UVA irradiation at earlier time points than vehicle pretreatment did, and three main constituents of WEP showed similar effects. Furthermore, WEP pretreatment also accelerated Nrf2 nuclear translocation after UVA irradiation.
  
  
  CONCLUSIONS
  Our findings indicated that WEP acts as an early inducer of HO-1 and rapid activator of Nrf2 to protect against UVA-induced oxidative stress.
authors.affiliation: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, 501-1196, Japan. saito.yakkou@gmail.com.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, 501-1196, Japan. tsuruma@gifu-pu.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.affiliation: Nagaragawa Research Center, Api.Co., Ltd., 692-3 Nagara, Gifu, 502-0071, Japan. ichihara-kenji@api3838.co.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichihara
authors.affiliation: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, 501-1196, Japan. shimazawa@gifu-pu.ac.jp.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, 501-1196, Japan. hidehara@gifu-pu.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D061745:Antioxidant Response Elements / Q000187:drug effects; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000528:radiation effects; D010936:Plant Extracts / Q000494:pharmacology; D011429:Propolis; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; C472707:caffeoylquinic acid; D011801:Quinic Acid; D011429:Propolis; D051547:Heme Oxygenase-1