title: EGb-761 prevents ultraviolet B-induced photoaging via inactivation of mitogen-activated protein kinases and proinflammatory cytokine expression.
abstract: BACKGROUND
  EGb-761 is an antioxidant and anticarcinogen; however, its role as a photoprotector remains unknown.
  
  
  OBJECTIVE
  To determine whether EGb-761 photoprotects human dermal fibroblasts and BALB/c mice skin against ultraviolet B (UVB) light irradiation.
  
  
  METHODS
  To simulate chronic photodamage, shaved BALB/c mice were exposed to UVB irradiation (90mJ/cm(2)) thrice weekly for 3 months. EGb-761 (2mg/cm(2)) was topically applied 1h before irradiation to evaluate its effect. The mechanisms by which EGb-761 protects the skin from photodamage were evaluated by immunohistochemical analysis, enzyme-linked immunosorbent assay (ELISA), and Western blotting.
  
  
  RESULTS
  In BALB/c mice, the signs of photoaging or photodamage, such as coarse wrinkle formation, epidermal hyperplasia, and elastic fiber degeneration, markedly reduced with the topical application of EGb-761. Western blot and ELISA revealed that the activation of MMP-1 in cultured fibroblasts markedly diminished after pretreatment with EGb-761. In addition, EGb-761 inhibited UVB-induced overexpression by the fibroblasts of the proinflammatory cytokines, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α. The phosphorylation of the mitogen-activated protein kinase (MAPK) signal transduction pathway components, including extracellular signal-regulated kinase, C-Jun N-terminal kinase, and p38, which are induced by UV irradiation, was significantly inhibited in vivo and in vitro. EGb-761 also diminished the generation of UVB-induced reactive oxygen species (ROS).
  
  
  CONCLUSIONS
  EGb-761 photoprotects mice and cultured fibroblasts, inhibits the UVB-induced phosphorylation of MAPK pathway components, and reduces the expression of the proinflammatory cytokines by suppressing ROS generation. Thus, topically applied EGb-761 may be a promising photoprotective agent.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Dermatology, National Yang Ming University, Taipei, Taiwan, ROC; Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: An-Na
authors.initials: AN
authors.lastname: Chiang
authors.affiliation: Department of Dermatology, National Yang Ming University, Taipei, Taiwan, ROC; Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Han-Nan
authors.initials: HN
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Dermatology, National Yang Ming University, Taipei, Taiwan, ROC; Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: ytchang@vghtpe.gov.tw.
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Chang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects; D020441:Ginkgo biloba; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects*; D013473:Sunscreening Agents / Q000494:pharmacology*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000096983:Ginkgo Extract
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D020781:Matrix Metalloproteinase 1; D020928:Mitogen-Activated Protein Kinases; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013473:Sunscreening Agents; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract
keywords: BALB/c mice; Cytokines; EGb-761; Matrix metalloproteinase; Mitogen activated protein kinase; Ultraviolet irradiation