Fisetin Ameliorated Photodamage by Suppressing the Mitogen-Activated Protein Kinase/Matrix Metalloproteinase Pathway and Nuclear Factor-κB Pathways

J Agric Food Chem. 2015 May 13;63(18):4551-60. doi: 10.1021/jf502500t. Epub 2015 Apr 29.


Ultraviolet (UV) irradiation is one of the most important extrinsic factors contributing to skin photodamage. After UV irradiation, a series of signal transductions in the skin will be activated, leading to inflammatory response and photoaged skin. In this study, fisetin, a flavonol that exists in fruits and vegetables, was investigated for its photoprotective effects. The results revealed that 5-25 μM fisetin inhibits cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP)-1, MMP-3, MMP-9 expression induced by ultraviolet B (UVB) irradiation in human skin fibroblasts. In addition, fisetin suppressed UVB-induced collagen degradation. With regard to its effect on upper-stream signal transduction, we found that fisetin reduced the expression of ultraviolet (UV)-induced ERK, JNK, and p38 phosphorylation in the mitogen-activated protein kinase (MAP kinase) pathway. Furthermore, fisetin reduced inhibitor κB (IκB) degradation and increased the amount of p65, which is a major subunit of nuclear factor-κB (NF-κB), in cytoplasm. It also suppressed NF-κB translocated to the nucleus and inhibited cAMP response element-binding protein (CREB) Ser-133 phosphorylation level in the phosphoinositide 3-kinase/protein kinase B/CREB (PI3K/AKT/CREB) pathway. Finally, fisetin inhibited UV-induced intracellular reactive oxygen species (ROS), prostaglandin E2 (PGE2), and nitric oxide (NO) generation. The mentioned effects and mechanisms suggest that fisetin can be used in the development of photoprotective agents.

Keywords: CREB; MAP kinase; NF-κB; fisetin; matrix metalloproteinase; photodamage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / radiation effects
  • Flavonoids / pharmacology*
  • Flavonols
  • Humans
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Radiation-Protective Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Skin / drug effects
  • Skin / enzymology
  • Skin / radiation effects
  • Ultraviolet Rays


  • Flavonoids
  • Flavonols
  • NF-kappa B
  • Radiation-Protective Agents
  • Reactive Oxygen Species
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1
  • fisetin