Dl-3-n-butylphthalide attenuates acute myocardial infarction by inhibiting the binding of Nrf2/Keap1.

Acute myocardial infarction (AMI) is a prevalent cardiovascular condition often encountered in clinics. It is characterized by an imbalance in the myocardial oxygen supply and demand and is thought to be associated to cell apoptosis and oxidative stress. Dl-3-n-butylphthalide (NBP), a natural product extracted from celery for the clinical treatment of ischemic stroke, may mitigate the effects of myocardial infarction. To test this hypothesis, isoproterenol (ISO) which is a β-adrenoceptor agonist, was used to simulate the metabolic and morphological abnormalities of AMI. The results demonstrated that NBP significantly alleviated ISO-induced cardiac dysfunction, showing beneficial effects on cardiac inflammation, apoptosis, fibrosis, and mitochondrial damage. Western blotting (WB), and qRT-PCR suggest that NBP may regulate the degradation of nuclear factor erythroid 2-related factor 2 (Nrf2). Further experiments revealed that NBP blocks the binding of Kelch-like ECH-associated protein-1 (Keap1) and Nrf2 and then inhibits the ubiquitination degradation of Nrf2. This study identifies NBP as a potent therapeutic agent for ISO-induced cardiac dysfunction by inhibiting Nrf2-Keap1 binding.