5,7-Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB-induced MMP expression in human skin fibroblast cells

Peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear hormone receptor superfamily, are a family of ligand-activated transcription factors that consist of three isotypes (PPAR a, d and ?). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARa/? in recent years have revealed their importance in age-related inflammation and photoaging as regulators of cytokines, matrix metalloproteinases (MMPs) and nuclear factor-kappa B (NF-?B). We evaluated the ability of the PPARa/? activator 5,7-dimethoxyflavone (5,7-DMF) to inhibit ultraviolet B (UVB)-induced MMP expression in Hs68 human skin fibroblasts. Hs68 cells were treated with 5,7-DMF and then exposed to UVB irradiation. MMP expression, production and activity were determined by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and gelatin zymography. PPARa/? expression, catalase expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1) and NF-?B signalling were evaluated by Western blot analysis. PPARa/? activity was assessed with the GAL4/PPARa/? transactivation assay. We found that 5,7-DMF strongly decreased MMP expression, production and activity. In addition, 5,7-DMF significantly increased PPARa/? activation and catalase expression, thereby downregulating UVB-induced reactive oxygen species (ROS) production, ROS-induced MAPK signalling and downstream transcription factors. Finally, 5,7-DMF reduced I?Ba phosphorylation, blocked NF-?B p65 nuclear translocation, strongly suppressed proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8. 5,7-DMF prevents UVB-induced MMP expression by suppressing UVB-induced oxidative stress and age-related inflammation via NF-?B and MAPK/AP-1 pathways. Our findings suggest the usefulness of 5,7-DMF for preventing and treating skin photoaging.