Effect of Salvianolic Acid A on PTEN Pathway: Improvement of Isoprenaline-Induced Cardiac Remodeling

Abstract

Background: Salvianolic acid A (SAA) is a biologically active compound that has anti-oxidative and anti-inflammatory pharmacological effects. There are limited studies on its pharmacological properties and role in cardiac remodeling. Therefore, this study aims to investigate the role and underlying mechanisms of SAA in cardiac remodeling in a mouse model. Methods: A mouse model of cardiac remodeling was constructed through intraperitoneal injection of isoproterenol (ISO). Two weeks after administration, the hearts of the treated and control groups were removed for determination of the heart weight (HW), body weight (BW), and lung weight (LW) to determine HW/BW and LW/BW ratios. We performed hematoxylin-eosin (HE) analysis, Masson staining and Western blotting to observe changes in each group. Doppler Echocardiography was utilized to acquire M-mode images to measure the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). In addition, to further assess and validate the activation of the Phosphatase and tensin homolog (PTEN) signaling pathway in mice with cardiac remodeling treated with SAA, we employed VO-Ohpic as an additional experimental approach. Results: This study showed that treatment with SAA in mice significantly mitigated cardiac dysfunction, while ameliorating pathological alterations associated with cardiac hypertrophy and fibrosis in the context of cardiac remodeling. In addition, SAA could improve antioxidant levels and depress inflammation in myocardial remodeling. Furthermore, SAA achieves this by promoting the PTEN signaling pathway. Conclusion: SAA exhibits potential in improving cardiac remodeling and dysfunction, potentially through its modulation of oxidative stress via the Nuclear factor kappa-B pathway mediated by PTEN (PTEN/NF-κB) pathway. These results provide a theoretical foundation for future clinical investigations on the therapeutic effects of SAA in myocardial remodeling.