Fisetin inhibits TNF-α-induced inflammatory action and hydrogen peroxide-induced oxidative damage in human keratinocyte HaCaT cells through PI3K/AKT/Nrf-2-mediated heme oxygenase-1 expression.

Abstract

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.

• Authors: Seung-Hee Seo, Gil-Saeng Jeong
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 29 Issue 2 Pg. 246-253 (Dec 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 26590114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• Antioxidants
• Flavonoids
• Flavonols
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Oxidants
• Tumor Necrosis Factor-alpha
• Hydrogen Peroxide
• Heme Oxygenase-1
• Oncogene Protein v-akt
• fisetin

Topics

• Antioxidants (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Flavonoids (pharmacology)
• Flavonols
• Heme Oxygenase-1 (biosynthesis, genetics)
• Humans
• Hydrogen Peroxide (antagonists & inhibitors, toxicity)
• Inflammation (chemically induced, prevention & control)
• Keratinocytes (drug effects)
• NF-E2-Related Factor 2 (metabolism)
• Oncogene Protein v-akt (metabolism)
• Oxidants (toxicity)
• Oxidative Stress (drug effects)
• Phosphatidylinositol 3-Kinases (metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, toxicity)