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 c). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARa ⁄ c 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-jB). We evaluated the ability of the PPARa ⁄ c 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 ⁄ c expression, catalase expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1) and NF-jB signalling were evaluated by Western blot analysis. PPARa ⁄ c activity was assessed with the GAL4 ⁄ PPARa ⁄ c transactivation assay. We found that 5,7-DMF strongly decreased MMP expression, production and activity. In addition, 5,7-DMF significantly increased PPARa ⁄ c 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 IjBa phosphorylation, blocked NF-jB 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-jB and MAPK ⁄ AP-1 pathways. Our findings suggest the usefulness of 5,7-DMF for preventing and treating skin photoaging.

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Exposure to ultraviolet (UV) light causes premature skin aging that is associated with upregulated matrix metalloproteinases (MMPs) and decreased collagen synthesis. Macelignan, a natural lignan compound isolated from Myristica fragrans HOUTT. (nutmeg), has been reported to possess antioxidant and antiinflammatory activities. This study assessed the effects of macelignan on photoaging and investigated its mechanisms of action in UV-irradiated human skin fibroblasts (Hs68) by reverse transcription-polymerase chain reaction, Western blot analysis, 2′,7′-dichlorofluorescein diacetate assay, and enzyme-linked immunosorbent assay. Our results show that macelignan attenuated UV-induced MMP-1 expression by suppressing phosphorylation of mitogen-activated protein kinases (MAPKs) induced by reactive oxygen species. Macelignan also increased type I procollagen expression and secretion through transforming growth factor β (TGF-β)/Smad signaling. These findings indicate that macelignan regulates the expression of MMP-1 and type I procollagen in UV-irradiated human skin fibroblasts by modulating MAPK and TGF-β/Smad signaling, suggesting its potential as an efficacious antiphotoaging agent.Key words macelignan; matrix metalloproteinase-1; type I procollagen; mitogen-activated protein kinase; UV irradiation; reactive oxygen species Skin aging, which causes wrinkling, sagging and roughness, can be divided into two distinct processes: intrinsic aging and photoaging. Photodamage and premature skin aging is caused by ultraviolet (UV) irradiation, which increases the synthesis of matrix metalloproteinases (MMPs).1) MMP upregulation in skin fibroblasts accelerates the degradation of dermal collagen, which confers tensile strength.2) Skin aging is characterized by reductions in type I collagen, the primary component of the extracellular matrix (ECM), which provides structural support to the skin dermis.3) Therefore, natural compounds that decrease the MMP production and increase procollagen synthesis may have potential for the prevention and treatment of photoaging. Most are secreted as inactive proenzymes (proMMPs) that are activated primarily by proteolytic cascades, generally catalyzed by neutral proteinases. MMP-1 is primarily responsible for degradation of ECM. 4)UV irradiation also leads to the generation of reactive oxygen species (ROS), direct or indirect DNA damage, and inflammatory response and damage to ECM integrity. 5)