We previously reported that
Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against
cardiac hypertrophy in rats induced by
isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the
hypertrophy and Nuclear Factor κB (NF-κB)/
Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α (PGC-1α) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the
cardiac hypertrophy with focuses on the NF-κB/PGC-1α signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart
weight/body weight and Left ventricular
weight/body weight, improved the cardiac hemodynamics, down-regulated
mRNA expression of
Atrial Natriuretic Peptide (
ANP) and
Brain Natriuretic Peptide (BNP), increased the ratio of
ATP/
AMP, and decreased the content of Free Fat
Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and
protein content, down-regulated
mRNA expression of
ANP and BNP, increased the ratio of
ATP/
AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the
protein expression of ATP5D, subunit of
ATP synthase and PGC-1α, inhibited translocation of p65, subunit of NF-κB into nuclear fraction in both rats and NRVMs compared with Iso alone.
Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with
siRNA decreased the surface areas and increased PGC-1α expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced
cardiac hypertrophy through regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.