Foeniculum vulgare Mill. increases cytosolic Ca2+ concentration and inhibits store-operated Ca2+ entry in vascular endothelial cells.

Abstract

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 Ca2+-induced store-operated Ca2+ entry (SOCE) into vascular endothelial (EA) cells and their mechanisms of action. Components of fennel oil were analyzed by gas chromatography-mass spectrometry. Cytosolic Ca2+ concentration ([Ca2+]c) in EA cells was determined using Fura-2 fluorescence. In the presence of extracellular Ca2+, fennel oil significantly increased [Ca2+]c in EA cells; this increase was significantly inhibited by the Ca2+ channel blockers La3+ and nifedipine. In contrast, fennel oil induced [Ca2+]c was significantly lower in Ca2+-free solution, suggesting that fennel oil increases [Ca2+]c mainly by enhancing Ca2+ influx into EA cells. [Ca2+]c 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 (La3+), a non-selective cation channel (NSC) blocker; 2-aminoethoxydiphenyl borane (2-APB), an inositol 1,4,5-triphosphate (IP3) receptor inhibitor and SOCE blocker; and U73122, an inhibitor of phospholipase C (PLC). Further, SOCE was more strongly inhibited by La3+ plus fennel oil or trans-anethole than by La3+ alone. These findings suggest that fennel oil and trans-anethole significantly inhibit SOCE-induced [Ca2+]c increase in vascular endothelial cells and that these reactions may be mediated by NSC, IP3-dependent Ca2+ mobilization, and PLC activation.