New insights into the pharmacological potential of plant flavonoids in the catecholamine system.

Flavonoids are biologically active polyphenolic compounds widely distributed in plants. Recent research has focused on high dietary intake of flavonoids because of their potential to reduce the risks of diseases such as cardiovascular diseases, diabetes, and cancers. We report here the effects of plant flavonoids on catecholamine signaling in cultured bovine adrenal medullary cells used as a model of central and peripheral sympathetic neurons. Daidzein (0.01 - 1.0 μM), a soy isoflavone, stimulated (14)C-catecholamine synthesis through plasma membrane estrogen receptors. Nobiletin (1.0 - 100 μM), a citrus polymethoxy flavone, enhanced (14)C-catecholamine synthesis through the phosphorylation of Ser19 and Ser40 of tyrosine hydroxylase, which was associated with (45)Ca(2+) influx and catecholamine secretion. Treatment with genistein (0.01 - 10 μM), another isoflavone, but not daidzein, enhanced [(3)H]noradrenaline uptake by SK-N-SH cells, a human noradrenergic neuroblastoma cell line. Daidzein as well as nobiletin (≥ 1.0 μM) inhibited catecholamine synthesis and secretion induced by acetylcholine, a physiological secretagogue. The present review shows that plant flavonoids have various pharmacological potentials on the catecholamine system in adrenal medullary cells, and probably also in sympathetic neurons.