Neferine Pretreatment Attenuates Isoproterenol-Induced Cardiac Injury Through Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats

Heart attacks, also known as myocardial infarctions (MIs), are one of the main reasons people die from cardiovascular diseases (CVDs) worldwide. Neferine, an alkaloid derived from Nelumbo nucifera seeds, has garnered interest due to its purported medicinal effects. In the current research, we induced MI in rats using the beta-adrenergic agonist isoproterenol to investigate whether neferine can improve cardiac dysfunction. The rats were separated into four groups: control, isoproterenol (ISO), and two treatment groups received neferine at doses of 10 or 20 mg/kg once daily for 28 days. On days 27 and 28, the groups undergoing treatment were administered with an ISO injection. Results showed that pretreatment with neferine strongly protected against changes in lipid profiles and cardiac functional markers in ISO-administered rats. Neferine attenuated histopathologic changes, collagen deposition, and myocardial fibrosis in rats administered ISO. Neferine pretreatment significantly inhibited the oxidative stress, inflammatory, and apoptotic markers in the heart of ISO-injected rats. This was achieved through Nrf2/Keap1/ARE signaling stimulation, TLR4/NF-kappa B/MAPK-mediated signaling inhibition, and activation of the intrinsic apoptotic pathway. Using CB-Dock-2, researchers determined that neferine has a high binding affinity with protein receptors that are pivotal in several biological processes. In conclusion, the study provides strong evidence that pretreatment with neferine protects rats from ISO-induced heart damage.