We previously reported that Astragalus
polysaccharide (APS) extracted from Chinese medicine Astragalus membranaceus (Fisch.) Bge, attenuates
hypertrophy of neonatal rat ventricular myocytes (NRVMs) induced by
isoproterenol (Iso). The present study was designed to investigate the effects and the possible mechanism of APS on Iso-induced
hypertrophy in rats and NRVMs with focus on
tumor necrosis factor α (TNF-α)/
peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) signaling mediated energy biosynthesis. 36-Week old rats were randomly divided into 3 groups: (1) Control, rats received vehicle; (2) Iso, rats received
isoproterenol injections; (3) Iso+APS, rats received
isoproterenol injections and APS. NRVMs were divided into similar groups as rats. The results showed that combination of APS with Iso significantly attenuated the pathological changes, reduced the ratios of heart
weight/body weight (HW/BW) and left ventricular weight/BW (LVW/BW), improved the cardiac hemodynamics, down-regulated
mRNA and
protein expression of
atrial natriuretic peptide (
ANP), increased the ratios of
ATP/
ADP and
ATP/
AMP, and decreased the content of
free fatty acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with APS significantly decreased the surface area and
protein content, down-regulated
mRNA and
protein expression of
ANP, increased the ratios of
ATP/
ADP and
ATP/
AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, APS increased the
protein expressions of ATP5D, the σ subunit of
ATP synthase, PGC-1α and
pyruvate dehydrogenase kinase 4 (PDK4) in tissue and NRVMs respectively and inhibited the production of TNF-α in serum and culture medium compared with Iso alone. The results suggested that APS attenuates Iso-induced
cardiac hypertrophy through regulating TNF-α/PGC-1α signaling mediated energy biosynthesis.