Astragaloside IV is widely used for the treatment of
cardiovascular diseases in China. However, its role in
cardiac hypertrophy remains unclear. In this study, we aim to determine the protective effects of
astragaloside IV on myocardial
hypertrophy induced by
lipopolysaccharide and to identify their precise molecular and cellular mechanisms. Cell size, reorganization of actin filaments, and
ANP and BNP
mRNA expression were used as indices of
hypertrophy; CaN and GATA-4 expression and the distribution of NFAT-3 in both cytoplasm and nucleus were determined by Western blot analysis; Ca2+ transient in
Fura-2/AM-loaded cells was measured by Till image system. Our data demonstrated that
lipopolysaccharide challenge induced
cardiac hypertrophy, increased resting Ca2+ transient level, promoted activation of CaN and GATA-4, and enhanced nuclear translocation of NFAT-3. Administration of
astragaloside IV (16, 32, and 64 µM) 1 h prior to
lipopolysaccharide stimulation dose-dependently attenuated
cardiac hypertrophy induced by
lipopolysaccharide. Further studies demonstrated that
astragaloside IV inhibited the increment of the resting intracellular free Ca2+, and its effect was similar to
verapamil. Moreover,
astragaloside IV also inhibited the activation of CaN and GATA-4, and the nuclear translocation of NFAT-3 induced by
lipopolysaccharide. In conclusion, our results revealed that
astragaloside IV had the potential to protect against
cardiac hypertrophy through Ca2+-mediated CaN signaling pathways.