Novel action of lignans isolated from Hernandia nymphaeifolia on Ca²⁺ signaling in renal tubular cells

The effect of five lignans, epi-aschantin, epi-magnolin, epi-yangambin, deoxypodophyllotoxin and yatein, isolated from Hernandia nymphaeifolia on Ca²⁺ signaling in Madin-Darby canine kidney cells was examined using fura-2 as a Ca²⁺ indicator. These lignans at concentrations between 10 and 100 μM increased [Ca²⁺]_i in a concentration-dependent manner. Removal of extracellular Ca²⁺ abolished the Ca²⁺ signals evoked by 50 μM of the lignans. La³⁺(50 μM) abolished the Ca²⁺ signals induced by 100 μM of epi-aschantin, epi-magnolin and epi-yangambin, and 20 μM deoxypodophyllotoxin, but inhibited by 60% 50 μM yatein-induced responses. All five lignans (50-100 μM) inhibited by 42-65% thapsigargin-induced capacitative Ca²⁺ entry, and inhibited by 23-61% thapsigargin-induced intracellular Ca²⁺ release. Epi-yangambin (100 μM), epi-magnolin (100 μM), and epi-aschantin (100 μM) inhibited by 8-38% 10 μM ATP-induced Ca²⁺ release. Trypan blue exclusion revealed that incubation with deoxypodophyllotoxin or yatein (but not the other lignans) decreased cell viability in a concentration-dependent manner. Together, the results suggest that, in renal tubular cells, these lignans exert multiple actions on Ca²⁺ signaling. They caused Ca²⁺ influx but reduced thapsigargin-induced capacitative Ca²⁺ entry and also thapsigargin- and ATP-induced Ca²⁺ release. Additionally, deoxypodophyllotoxin and yatein may be cytotoxic.