Foeniculum vulgare extract and its constituent, trans-anethole, inhibit UV-induced melanogenesis via ORAI1 channel inhibition

Background: Ultraviolet radiation exposure is the most important cause of extrinsic skin aging (photoaging), which causes skin wrinkling and hyperpigmentation. Although many factors are involved in the photoaging process, calcium release-activated calcium channel protein 1 (ORAI1) has been reported to be involved in UV-induced melanogenesis. Objective: The aim of the present study was to find inhibitory effects of the extract of Foeniculum vulgare (fennel) fruits on ORM ion channels and UV-induced melanogenesis in melanoma cells and to identify its active constituents. Methods: Active compounds were isolated and quantitatively analyzed. An electrophysiological assay was performed by using the whole-cell patch-clamp technique. Intracellular free calcium concentration was measured by Fura-2. Tyrosinase activity was evaluated by levodopa colorimetry. Effects of the most active compound on cell viability of murine B16F10 melanoma cells and inhibition of melanin content after UVB irradiation were determined. Results: E vulgare fruits extract and its hexane fraction strongly blocked ORAI1 currents and tyrosinase activity and significantly inhibited UV-induced melanogenesis. Of the 13 compounds isolated from the hexane fraction, trans-anethole (TA) exhibited inhibitory effects on ORAI1 (IC50=8.954 +/- 136 mu M) and increased cytoplasmic Ca2+ concentrations in response. TA inhibited UV-induced melanogenesis without affecting tyrosinase activity. Conclusion: Our findings suggest that the fruits extract of E vulgare and its active constituent, TA, provide a possible novel approach for treating and preventing UV-induced melanogenesis. (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.