Potential cardioprotective and regenerative effects of the fluorinated benzothiazole derivative AS09 in the myocardial infarction-induced zebrafish.

Myocardial infarction (MI), a significant complication of coronary artery disease (CAD), results from prolonged myocardial ischemia. Generally, MI is caused by the rupture of an atherosclerotic plaque and thrombus formation. Among various pharmaceutical therapies and interventions, percutaneous coronary intervention (PCI) restores blood flow to the heart through reperfusion. These therapies do not target any of the signaling pathways involved in cardiac tissue repair post-MI. Specifically, the JAK2/STAT3 pathway is a key mediator of cardiac repair and defence mechanisms. This study investigated the cardioprotective efficacy of a novel fluorinated benzothiazole derivative, AS09. The in silico studies preliminarily revealed the potential interactions of AS09 with MI targets (JAK2, GSK3B, and PIK3CA). Behavioural Assays determined that AS09 significantly improved anxiety and increased locomotion. Biochemical assay showed that AS09 significantly increased the levels of antioxidant enzymes (SOD and CAT) and reduced oxidative stress (MDA) and cell death (LDH). Gene expression analyses further exhibited the decreased expression in inflammation and apoptosis (tnf-α, nf-κb, and Caspase-3). Whereas, increased expression of the antiapoptosis (bcl-2) and cardiac function (myl7, vmhc) associated genes suggests the potential for regeneration by AS09. The reduced myocardial fibrosis and increased structural repair observed at 28 days post-treatment (confirmed by histological analysis with H&E and MTS staining) indicate that AS09 has cardioprotective and regenerative properties. Additionally, these data preliminarily support the cardio-protective and regenerative potential of AS09, with in silico predictions suggesting involvement of the JAK2/STAT3 signaling pathway.