Foeniculum Vulgare Mill. Increases Cytosolic Ca Concentration and Inhibits Store-operated Ca Entry in Vascular Endothelial Cells

This study assessed the effects of essential oil of Foeniculum vulgare Mill. (fennel oil) and of trans-anethole, the main component of fennel oil, on extracellular Ca-induced store-operated Ca entry (SOCE) into vascular endothelial (EA) cells and their mechanisms of action. Components of fennel oil were analyzed by gas chromatography-mass spectrometry. Cytosolic Ca concentration ([Ca]) in EA cells was determined using Fura-2 fluorescence. In the presence of extracellular Ca, fennel oil significantly increased [Ca] in EA cells; this increase was significantly inhibited by the Ca channel blockers La and nifedipine. In contrast, fennel oil induced [Ca] was significantly lower in Ca-free solution, suggesting that fennel oil increases [Ca] mainly by enhancing Ca influx into EA cells. [Ca] mobilization by trans-anethole was similar to that of fennel oil. Moreover, SOCE was suppressed by fennel oil and trans-anethole. SOCE was also attenuated by lanthanum (La), a non-selective cation channel (NSC) blocker; 2-aminoethoxydiphenyl borane (2-APB), an inositol 1,4,5-triphosphate (IP) receptor inhibitor and SOCE blocker; and U73122, an inhibitor of phospholipase C (PLC). Further, SOCE was more strongly inhibited by La plus fennel oil or trans-anethole than by La alone. These findings suggest that fennel oil and trans-anethole significantly inhibit SOCE-induced [Ca] increase in vascular endothelial cells and that these reactions may be mediated by NSC, IP-dependent Ca mobilization, and PLC activation.