The effect of five lignans isolated from Hernandia nymphaeifolia on estrogenic compounds (17beta-estradiol, tamoxifen and clomiphene)-induced Ca(2+) mobilization in human neutrophils was investigated. The five lignans were epi-yangambin, epi-magnolin, epi-aschantin, deoxypodophyllotoxin and yatein. In Ca(2+)-containing medium, the lignans (50-100 microM) inhibited 10 microM 17beta-estradiol- and 5 microM tamoxifen-induced increases in intracellular free Ca(2+) levels ([Ca(2+)](i)) without changing 25 microM clomiphene-induced [Ca(2+)](i) increase. 17beta-estradiol and tamoxifen increased [Ca(2+)](i) by causing Ca(2+) influx and Ca(2+) release because their responses were partly reduced by removing extracellular Ca(2+). In contrast, clomiphene solely induced Ca(2+) release. The effect of the lignans on these two Ca(2+) movement pathways underlying 17beta-estradiol- and tamoxifen-induced [Ca(2+)](i) increases was explored. All the lignans (50-100 microM) inhibited 10 microM 17beta-estradiol-and 5 microM tamoxifen-induced Ca(2+) release, and 17beta-estradiol-induced Ca(2+) influx. However, only 100 microM epi-aschantin was able to reduce tamoxifen-induced Ca(2+) influx while the other lignans had no effect. Collectively, this study shows that the lignans altered estrogenic compounds-induced Ca(2+) signaling in human neutrophils in a multiple manner.