Fisetin Inhibits UVA-Induced Expression of MMP-1 and MMP-3 through the NOX/ROS/MAPK Pathway in Human Dermal

Hye-Yeon Jang1,2, Gi-Beum Kim1, Jeong-Mi Kim1

  • 1Department of Biochemistry and Molecular Biology, Institute for Medical Sciences, BK21FOUR 21st Century Medical Science Creative Human Resource Development Center, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea.

Insights

Fisetin, a plant flavonoid, protects skin cells from ultraviolet-A (UVA) damage by inhibiting inflammatory pathways. It reduces reactive oxygen species and matrix metalloproteinases, suggesting a novel therapeutic approach for skin protection.

Area of Science:

  • Dermatology and Photobiology
  • Molecular Biology
  • Natural Product Chemistry

Background:

  • Ultraviolet-A (UVA) radiation causes significant skin damage.
  • The precise mechanisms underlying UVA-induced skin damage are not fully understood.
  • Flavonoids, like fisetin, show potential therapeutic benefits in various diseases.

Purpose of the Study:

  • To investigate the protective mechanisms of fisetin against UVA-induced damage in human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs).
  • To elucidate the role of the NADPH oxidase (NOX)/reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) pathway in fisetin's protective effects.

Main Methods:

  • Cell culture of HDFs and HEKs exposed to UVA irradiation.
  • Assessment of fisetin's cytoprotective effects.
  • Measurement of matrix metalloproteinases (MMPs), pro-inflammatory cytokines, and ROS production.
  • Analysis of mRNA levels for NOX and MAPK/AP-1 related proteins.
  • Inhibition of NOX using siRNAs.

Main Results:

  • Fisetin demonstrated cytoprotective effects against UVA irradiation in HDFs and HEKs.
  • Fisetin suppressed the expression of MMP-1 and MMP-3.
  • Fisetin reduced pro-inflammatory cytokine mRNA levels and ROS production.
  • Fisetin downregulated MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels.
  • siRNAs targeting NOX 1-5 inhibited UVA-induced MMP-1 and MMP-3 expression.

Conclusions:

  • Fisetin effectively protects HDFs and HEKs from UVA-induced damage.
  • The protective mechanism involves the inhibition of the NOX/ROS/MAPK pathway.
  • Fisetin represents a potential therapeutic agent for mitigating UVA-induced skin damage.