Abstract
Ultraviolet (UV) radiation, particularly ultraviolet A (UVA), is known to play a major role in photoaging of the human skin. Many studies have demonstrated that UV exposure causes the skin cells to generate reactive oxygen species and activates the mitogen-activated protein kinase (MAPK) pathway. Previous studies have also demonstrated that cycloheterophyllin has an antioxidant effect and can effectively scavenge free radicals. Extending the aforementioned investigations, in this study, human dermal fibroblasts were used to investigate the protective effect of cycloheterophyllin against UV-induced damage. We found that cycloheterophyllin not only significantly increased cell viability, but also attenuated the phosphorylation of MAPK after UVA exposure. Furthermore, cycloheterophyllin could reduce hydrogen peroxide (H2O2) generation and down-regulate H2O2-induced MAPK phosphorylation. In the in vivo studies, the topical application of cycloheterophyllin before UVA irradiation significantly decreased trans-epidermal water loss (TEWL), erythema, and blood flow rate. These results indicate that cycloheterophyllin is a photoprotective agent that inhibits UVA-induced oxidative stress and damage, and could be used in the research on and prevention of skin photoaging.
Highlights
Ultraviolet (UV) irradiation is recognized to play a major role in photoaging and skin cancer [1, 2]
Foreskins were provided by the Mackay Memorial Hospital to the Fu Jen Catholic University with a notice stating an exemption from the institutional review board (IRB) (C10018), as no interaction occurred with the subjects and no identifiable information was made available to the researchers
We first used an MTT assay to evaluate whether cycloheterophyllin would induce cytotoxicity in the fibroblasts, and our results showed that cycloheterophyllin (0.1–1 μM) exhibited low cytotoxicity after 24 hours of treatment (Fig 1B)
Summary
Ultraviolet (UV) irradiation is recognized to play a major role in photoaging and skin cancer [1, 2]. Cycloheterophyllin (C30H30O7), a prenylflavone (Fig 1A), is isolated from Artocarpus heterophyllus, and has pharmacological and biological functions including anti-inflammatory effects, anti-platelet activities, and antioxidant properties [8,9,10,11]. It is unknown whether cycloheterophyllin can modulate the signaling pathways triggered by UVA in human dermal fibroblasts. The data generated by this study can assist in unraveling the molecular mechanisms underlying the photoprotective effects of cycloheterophyllin against UVA-induced damage in dermal fibroblasts [12]
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