Astragaloside IV treatment significantly inhibited HG/HF and hypoxia-induced apoptosis of H9c2. AS-IV inhibited activation of JNK and p38 signaling pathway while promoting the activation of EKR signaling pathway. AS-IV treatment rescued cardiac function, suppressed cardiac fibrosis and inflammation, and differently regulated the activation of MAPK signaling pathways. This evidence concerns the gene MAPK14 and fibrosis.