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.

Keywords: Cytosolic Ca(2+); Foeniculum vulgare Mill.; Store-operated Ca(2+) entry; Vascular endothelial cells; trans-anethole.