However, blend with ASIV significantly lowered the thickness of the ventricular wall, attenuated the narrowness of theThe cardiac hemohynamics ended up measured as explained in Resources and Approaches section. Data are 
offered as mean .D. (n = 8). P<0.01 vs controlP<0.01 vs Iso.LVEDP, Left ventricular end-diastolic pressure LVSP, Left ventricular systolic pressure +dp/dt, Maximal positive time derivative of developed pressure -dp/dt, Maximal negative time derivative of developed pressure. Iso: Isoproterenol ASIV: Astragaloside IV.ventricular cavity, decreased the ratios of HW/BW and LVW/BW and down-regulated the mRNA expression of ANP and BNP compared with Iso alone (Fig. 1), suggesting that downregulation of ANP and BNP at least partly explains the protection of ASIV on cardiac hypertrophy.To verify the protective effects of ASIV on cardiac hypertrophy in vivo, we cultured the NRVM cells and study the effects of ASIV on Iso induced hypertrophy in vitro. We found that NRVM treated with Iso alone demonstrated the increases in cell surface area, protein content and mRNA expression of ANP and BNP compared with normal control cells. Combination with ASIV resulted in significant decreases in cell surface area, protein content as well as mRNA expression of ANP and BNP compared with Iso alone (Fig. 2).Dysfunction of energy biosynthesis in cardiac mitochondria contributes to the hypertrophy. ATP5D, subunit of ATP synthase, is one of the enzymes responsible for the ATP synthesis in mitochondria. To explore the mechanisms underlying the protection of ASIV on cardiac hypertrophy, we examined the effects of ASIV on Iso induced dysfunction of cardiac energy biosynthesis of rats and NRVM. The results showed that treatment with Iso alone decreased the ratio of ATP/AMP and increased FFA content in both heart tissue and NRVM compared with normal control rats or cells, meanwhile decreased the protein expression of ATP5D in NRVM compared with control NRVM. However, treatment with ASIV significantly increased the ratio of ATP/AMP and reduced the FFP content in both rats and NRVM, and increased the protein expression of ATP5D in NRVM compared with Iso alone (Fig. 3). The results suggest that ASIV prevent cardiac hypertrophy at least partly through improvement of cardiac energy biosynthesis which might be attributed to the up-regulation of ATP5D protein expression.NF-B/PGC-1 signaling is closely related to the regulation of ATP5D, subsequently affecting the energy biosynthesis. We finally examined whether NF-B/PGC-1 signaling gets involved in the correction of cardiac energy biosynthesis dysfunction by ASIV, subsequently contributing to the protection against cardiac hypertrophy. The results showed that treatment with Iso alone decreased the protein expression of p65, the subunit of NF-B in cytoplasm while increased the expression of p65 in nuclear fraction, and decreased PGC-1 protein expression in both rat and NRVM compared with normal control rat or cells. However, combination of ASIV significantly decreased the p65 expression in nuclear fraction while increased the expression of p65 in cytoplasm meanwhile increased the PGC-1 expression compared with Iso alone (Fig. 4). Parthenolide, the specific inhibitor of p65, exerted similar effects as ASIV on PGC-1 expression in cells. The results7791070 suggested that ASIV exhibits the improvement of dysfunction in cardiac energy biosynthesis at least partly through regulation of NF-B/PGC1 signaling.To confirm the down-regulation of PGC-1 by NF-B activation, we knocked down the p65 using siRNA to observe the effect of inactivation of NF-B on PGC-1 protein expression in NRVMs treated by Iso. We found that MCE Chemical Haloperidol (D4′) knockdown of p65 decreased the surface area and Fig 1. Effects of ASIV on index of cardiac hypertrophy and mRNA expression of ANP and BNP in hypertrophic heart.