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Astragaloside IV, atractylenolide I, and prim-Oglucosylcimifugin are main medicinal components of the traditional Chinese medicine prescription Yu-ping-feng which is composed of three herbs: Astragalus membranaceus, Atractylodes macrocephala, and Saposhnikovia divaricata. This study is aimed to assess the influence of atractylenolide I and prim-O-glucosylcimifugin on the pharmacokinetic profile of astragaloside IV so as to investigate the pharmacokinetic mechanisms of the Yu-ping-feng prescription. Fifteen Sprague Dawley rats were randomized to three groups; astragaloside IV, astragaloside IV plus atractylenolide I, and a combination of astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin were respectively administered to rats of these three groups via intragastric gavage. Serum samples were collected at different times after drug administration, and serum concentrations of astragaloside IV and atractylenolide I were simultaneously detected using HPLC-electrospray ionization-MS. Compared with administration of astragaloside IV alone, concentrations of astragaloside IV in the serum were significantly increased when it was given in combination with atractylenolide I or atractylenolide I+prim-O-glucosylcimifugin, with higher values for Cmax (p = 0.019 and p = 0.033 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively) and AUC (p = 0.0052 and p = 0.0047 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim- O-glucosylcimifugin groups, respectively). Improvement in mean oral Cmax and mean systemic serum exposure because of the pharmacokinetic interaction between astragaloside IV and atractylenolide I might explain the rationale for the use of multiple herbs in Yu-ping-feng and of combinations of A.membranaceus and A. macrocephala. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]