title: 23-Hydroxytormentic acid protects human dermal fibroblasts by attenuating UVA-induced oxidative stress.
abstract: BACKGROUND
  Ultraviolet A (UVA), one of the major components of sunlight, can penetrate the dermal layer of the skin and generate reactive oxygen species (ROS). It causes alterations in the dermal connective tissue and gene expression, inflammation, photoaging, and DNA damage.
  
  
  OBJECTIVE
  Therefore, the harmful effects of UVA and strategies to reduce it have been consistently investigated. 23-Hydroxytormentic acid (23-HTA) has been demonstrated to improve drug-induced nephrotoxicity and exhibit several free radical scavenging effects with other molecules. Therefore, the aim of this study was to investigate the anti-inflammatory effects and extracellular matrix (ECM) reconstructive activity of 23-HTA in UVA-irradiated normal human dermal fibroblasts (NHDFs).
  
  
  METHODS
  The antioxidant capacity of 23-HTA was determined by examining its scavenging activities against hydrogen peroxide, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and diphenylpicrylhydrazyl in vitro. Its effect on cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide, and 2,7-dichlorofluorescin diacetate was used to investigate intracellular ROS scavenging activity. The mRNA levels of antioxidant enzymes and pro-inflammatory cytokines were detected using quantitative real-time polymerase chain reaction. A senescence-associated β-galactosidase (SA-β-gal) staining kit was used to assess senescent cells.
  
  
  RESULTS
  23-HTA showed antioxidant capacity mediated by ROS scavenging and regulation of antioxidant-related gene expression. Further, the SA-β-gal analysis and mRNA expression of matrix metalloproteinases and type I procollagen suggested that 23-HTA regulates the gene expression of ECM proteins and cellular senescence under UVA-irradiated conditions.
  
  
  CONCLUSIONS
  In conclusion, 23-HTA protects against and attenuates UVA-induced oxidative stress in NHDFs likely via the nuclear factor erythroid-derived 2-like 2 signaling pathway.
authors.affiliation: Department of Dermatology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Hae Jeong
authors.identifier: http://orcid.org/0000-0001-5824-8103
authors.initials: HJ
authors.lastname: Youn
authors.affiliation: Korea Institute for Skin and Clinical Sciences, GeneCellPharm Corporation, Cheongju-si, Chungcheongbuk-do, Korea.
authors.forename: Ki Bbeum
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Korea Institute for Skin and Clinical Sciences, GeneCellPharm Corporation, Cheongju-si, Chungcheongbuk-do, Korea.
authors.forename: Hyo-Sun
authors.initials: HS
authors.lastname: Han
authors.affiliation: Korea Institute for Skin and Clinical Sciences, GeneCellPharm Corporation, Cheongju-si, Chungcheongbuk-do, Korea.
authors.forename: In-Sook
authors.initials: IS
authors.lastname: An
authors.affiliation: Department of Dermatology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Kyu Joong
authors.initials: KJ
authors.lastname: Ahn
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D052160:Benzothiazoles / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism; D002374:Catalase / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D010851:Picrates / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013451:Sulfonic Acids / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: C511643:23-hydroxytormentic acid; D000975:Antioxidants; D052160:Benzothiazoles; D001713:Biphenyl Compounds; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053583:Interleukin-1beta; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010851:Picrates; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013451:Sulfonic Acids; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D005979:Glutathione Peroxidase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D020781:Matrix Metalloproteinase 1
keywords: 23-hydroxytormentic acid; aging; antioxidants; fibroblast; inflammation; ultraviolet radiation