UVB-induced DNA damage, generation of reactive oxygen species, and inflammation are effectively attenuated by the flavonoid luteolin in vitro and in vivo

Free Radic Biol Med. 2011 May 1;50(9):1081-93. doi: 10.1016/j.freeradbiomed.2011.01.027. Epub 2011 Jan 31.

Abstract

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human keratinocytes resulting in skin inflammation, photoaging, and photocarcinogenesis. The flavonoid luteolin is one of the most potent antioxidative plant polyphenols. We investigated the UV protective and antioxidant properties of luteolin in human keratinocytes in vitro, ex vivo, and in vivo. Spectrophotometric measurements revealed extinction maxima of luteolin in the UVB and UVA range. UV transmission below 370 nm was <10%. In human skin, luteolin effectively reduced the formation of UVB-induced cyclobutane pyrimidine dimers. The free radical scavenging activity of luteolin was assessed in various cell-free and cell-based assays. In the cell-free DPPH assay the half-maximal effective concentration (EC₅₀) of luteolin (12 μg/ml) was comparable to those of Trolox (25 μg/ml) and N-acetylcysteine (32 μg/ml). In contrast, in the H₂DCFDA assay performed with UVB-irradiated keratinocytes, luteolin (EC₅₀ 3 μg/ml) was much more effective compared to Trolox (EC₅₀ 12 μg/ml) and N-acetylcysteine (EC₅₀ 847 μg/ml). Luteolin also inhibited both UVB-induced skin erythema and the upregulation of cyclooxygenase-2 and prostaglandin E₂ production in human skin via interference with the MAPK pathway. These data suggest that luteolin may protect human skin from UVB-induced damage by a combination of UV-absorbing, DNA-protective, antioxidant, and anti-inflammatory properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Antioxidants / pharmacology*
  • Cell Line
  • Chromans / pharmacology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytoprotection
  • DNA Damage
  • Dinoprostone / analysis
  • Dinoprostone / biosynthesis
  • Erythema / drug therapy
  • Erythema / pathology
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fluoresceins
  • Gene Expression
  • Humans
  • Inflammation / prevention & control
  • Inhibitory Concentration 50
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Keratinocytes / radiation effects
  • Luteolin* / pharmacology
  • Organ Culture Techniques
  • Oxidative Stress / drug effects
  • Pyrimidine Dimers / antagonists & inhibitors*
  • Pyrimidine Dimers / chemistry
  • Reactive Oxygen Species / metabolism
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology
  • Ultraviolet Rays / adverse effects
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • Chromans
  • Fluoresceins
  • Pyrimidine Dimers
  • Reactive Oxygen Species
  • Cyclooxygenase 2
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dinoprostone
  • Luteolin
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
  • Acetylcysteine