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J Dermatol Sci. 2016 Dec;84(3):305-313. doi: 10.1016/j.jdermsci.2016.09.017. Epub 2016 Sep 28.

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

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Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 780-714, Republic of Korea; Channelopathy Research Center (CRC), Dongguk University College of Medicine, 27 Dongguk-ro, Ilsan Dong-gu, Goyang 410-773, Republic of Korea.
Division of Bioscience, Dongguk University, Gyeongju 780-714, Republic of Korea. Electronic address:



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.


The aim of the present study was to find inhibitory effects of the extract of Foeniculum vulgare (fennel) fruits on ORAI1 ion channels and UV-induced melanogenesis in melanoma cells and to identify its active constituents.


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.


F. 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±1.36μM) and increased cytoplasmic Ca2+ concentrations in response. TA inhibited UV-induced melanogenesis without affecting tyrosinase activity.


Our findings suggest that the fruits extract of F. vulgare and its active constituent, TA, provide a possible novel approach for treating and preventing UV-induced melanogenesis.


Foeniculum vulgare; Melanogenesis; ORAI1 channel; Tyrosinase; Ultraviolet; trans-Anethole

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