Astragaloside IV inhibits isoprenaline-induced cardiac fibrosis by targeting the reactive oxygen species/mitogen-activated protein kinase signaling axis

Abstract

Cardiac fibrosis is considered an important pathological mechanism in the progression of cardiac remodeling and heart failure. Astragaloside IV (AsIV) is a major active ingredient in Astragalus membranaceus. In a preliminary experiment, it was demonstrated that this naturally occurring substance exhibited cardioprotective effects via preventing cardiomyocyte hypertrophy and apoptosis. The present study aimed to investigate the effects of AsIV on β-adrenergic receptor (β-AR)-mediated cardiac fibrosis, and the associated mechanism. Cell Counting Kit-8 (CCK-8) assay was used to examine the proliferation of rat cardiac fibroblast (CF) cultures. Collagen I secretion was detected by ELISA. Dihydroethidium was used to determine intracellular ROS levels. Western blotting was used to examine the expression level of total and phosphorylated mitogen-activated protein kinases (MAPKs). In the present study, the effects of AsIV on β-adrenergic receptor (β-AR)-mediated cardiac fibrosis were investigated, and the associated mechanism was revealed. Isoprenaline (ISO) is a selective β-AR agonist, and treatment with AsIV significantly inhibited (ISO)-triggered cardiac fibroblast proliferation and type I collagen synthesis. In addition, ISO resulted in a significant elevation of reactive oxygen species (ROS) levels and phosphorylation of the three profibrotic MAPKs, namely extracellular signal-regulated kinase, p38MAPK and c-Jun N-terminal kinase. AsIV effectively reversed the aforementioned ISO-induced alterations. In addition, N-acetylcysteine, a typical ROS scavenger, mimicked the inhibitory effects of AsIV on MAPK activation. The present study demonstrated that AsIV may inhibit ISO-induced cardiac fibrosis by suppressing ROS-mediated MAPK activation.