Therapeutic Effects of Salvianolic Acid B on Angiotensin II–Induced Atrial Fibrosis by Regulating Atrium Metabolism via Targeting AMPK/FoxO1/miR-148a-3p Axis

Abstract

Abstract The present study highlights the effects of salvianolic acid B (Sal B) on angiotensin II (Ang II)–activated atrial fibroblasts as well as the associated potential mechanism from the metabonomics perspective. Metabolic profile analysis performed an optimal separation of the Ang II and control group, indicating a recovery impact of Sal B on Ang II–activated fibroblasts (FBs). We found that metabolite levels in the Ang II + Sal B group were reversed to normal. Moreover, 23 significant metabolites were identified. Metabolic network analysis indicated that these metabolites participated in purine metabolism and FoxO signaling pathway. We found that Sal B activated AMP-activated protein kinase (AMPK) phosphorylation, which further promoted FoxO1 activation and increased miR-148a-3p level. We further verified that Sal B modulate the abnormal AMP, phosphocreatine, glutathione (GSH), and reactive oxygen species (ROS) production in Ang II–stimulated FBs. Collectively, Sal B can protect the Ang II–activated FBs from fibrosis and oxidative stress via AMPK/FoxO1/miRNA-148a-3p axis. Graphical abstract