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

Abstract

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.

Alleviation of Ultraviolet B-Induced Photodamage by Coffea arabica Extract in Human Skin Fibroblasts and Hairless Mouse Skin

“…Hs68 cells were cultured and exposed to UV irradiation as previously described [53]. Cells were incubated in DMEM without serum in the presence of CAE for 24 h after UVB irradiation.…”

“…Cells were collected and homogenized with lysis buffer as described in previous studies [53,54]. Equal protein amounts (30 μg) were loaded and separated on sodium dodecyl sulfate polyacrylamide gels and then transferred to a PVDF membrane.…”

“…Cells were cultivated on glass cover slips as described in a previous paper [53]. After UVB exposure, various concentrations of CAE (5–25 μg/mL) were added and incubated for 24 h. The cells were then immersed in 4% paraformaldehyde and incubated with nonfat milk containing Triton X-100.…”

Fisetin regulates astrocyte migration and proliferation in vitro

“…Previous studies have demonstrated that fisetin regulates the phosphoinositide 3-kinase (PI3K)/Akt and Erk signaling pathways (14–16). It has also been demonstrated that astrocyte migration is modulated by Rho GTPase/p21-activated kinase (PAK)/Erk-dependent signaling (17).…”

“…A recent study found that the Erk1/2 signaling pathway modulated the cytoskeleton dynamics of astrocytes in a scratch-wound model (17). Fisetin has been shown to play an important role in regulating the PI3K/Akt and Erk pathways (14,16,36). In the present study, fisetin downregulated the Akt and Erk phosphorylation levels in astrocytes in a dose-dependent manner, but had no effect on p38 expression and phosphorylation.…”