Oxidative skin damage and skin
inflammation play key roles in the pathogenesis of skin-related diseases.
Fisetin is a naturally occurring
flavonoid abundantly found in several vegetables and fruits.
Fisetin has been shown to exert various positive
biological effects, such as anti-
cancer, anti-proliferative, neuroprotective and anti-oxidative effects. In this study, we investigate the skin protective effects and anti-inflammatory properties of
fisetin in
hydrogen peroxide- and TNF-α-challenged human keratinocyte HaCaT cells. When HaCaT cells were treated with non-cytotoxic concentrations of
fisetin (1-20μM),
heme oxygenase (HO)-1
mRNA and
protein expression increased in a dose-dependent manner. Furthermore,
fisetin dose-dependently increased cell viability and reduced ROS production in
hydrogen peroxide-treated HaCaT cells.
Fisetin also inhibited the production of NO,
PGE2 IL-1β,
IL-6, expression of iNOS and COX-2, and activation of NF-κB in HaCaT cells treated with TNF-α.
Fisetin induced Nrf2 translocation to the nuclei. HO-1
siRNA transient transfection reversed the effects of
fisetin on cytoprotection, ROS reduction, NO,
PGE2, IL-1β,
IL-6, and TNF-α production, and NF-κB
DNA-binding activity. Moreover,
fisetin increased Akt phosphorylation and a PI3K pathway inhibitor (
LY294002) abolished
fisetin-induced cytoprotection and NO inhibition. Taken together, these results provide evidence for a beneficial role of
fisetin in skin
therapy.