title: Antagonizing effects and mechanisms of afzelin against UVB-induced cell damage.
abstract: Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human keratinocytes, resulting in skin inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effects of UV irradiation is essential. Therefore, in this study, we investigated the protective effects of afzelin, one of the flavonoids, against UV irradiation in human keratinocytes and epidermal equivalent models. Spectrophotometric measurements revealed that the afzelin extinction maxima were in the UVB and UVA range, and UV transmission below 376 nm was <10%, indicating UV-absorbing activity of afzelin. In the phototoxicity assay using the 3T3 NRU phototoxicity test (3T3-NRU-PT), afzelin presented a tendency to no phototoxic potential. In addition, in order to investigate cellular functions of afzelin itself, cells were treated with afzelin after UVB irradiation. In human keratinocyte, afzelin effectively inhibited the UVB-mediated increase in lipid peroxidation and the formation of cyclobutane pyrimidine dimers. Afzelin also inhibited UVB-induced cell death in human keratinocytes by inhibiting intrinsic apoptotic signaling. Furthermore, afzelin showed inhibitory effects on UVB-induced release of pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and prostaglandin-E2 in human keratinocytes by interfering with the p38 kinase pathway. Using an epidermal equivalent model exposed to UVB radiation, anti-apoptotic activity of afzelin was also confirmed together with a photoprotective effect at the morphological level. Taken together, our results suggest that afzelin has several cellular activities such as DNA-protective, antioxidant, and anti-inflammatory as well as UV-absorbing activity and may protect human skin from UVB-induced damage by a combination of UV-absorbing and cellular activities.
authors.affiliation: Biospectrum Life Science Institute, Seoungnam City, Gyunggi Do, Korea.
authors.forename: Seoung Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Seungbeom
authors.initials: S
authors.lastname: Kim
authors.forename: Jang-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Eui-Gyun
authors.initials: EG
authors.lastname: Kim
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D020552:Comet Assay; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008362:Mannosides / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D018384:Oxidative Stress; D044945:Proanthocyanidins / Q000494:pharmacology*; D011740:Pyrimidine Dimers / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014466:Ultraviolet Rays; D000093242:Interleukin-6 Inhibitors
chemical_list: D000975:Antioxidants; D015232:Dinoprostone; D015850:Interleukin-6; D008362:Mannosides; D044945:Proanthocyanidins; D011740:Pyrimidine Dimers; D011837:Radiation-Protective Agents; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C477954:afzelin