Aucubin protects against myocardial ischemia-reperfusion injury by regulating STAT3/NF-κB/HMGB-1 pathway.

The main characteristics of the myocardial ischemia/reperfusion injury (MI/RI) are oxidative stress, apoptosis, and an inflammatory response. Aucubin (AU) is an iridoid glycoside that possesses various biological properties and has been discovered to demonstrate antioxidant and anti-inflammatory impacts in pathological processes, such as ischemia-reperfusion. The objective of this research was to investigate if AU treatment could mitigate myocardial inflammation and apoptosis caused by ischemia/reperfusion (I/R) in both laboratory and animal models, and to elucidate its underlying mechanism. By ligating the coronary artery on the left anterior descending side, a successful MI/RI rat model was created. Additionally, H9C2 cells were subjected to hypoxia/reoxygenation (H/R) in order to imitate the injury caused by ischemia/reperfusion (I/R). Furthermore, various concentrations of AU were administered to H9C2 cells or rats before H/R stimulation or myocardial I/R surgery, respectively. In vitro, the assessment was conducted on cardiac function, inflammatory markers, and myocardial pathology. In vivo, we examined the viability of cells, as well as factors related to apoptosis and oxidative stress. Furthermore, the presence of proteins belonging to the STAT3/NF-κB/HMGB1 signaling pathway was observed both in vivo and in vitro. AU effectively improved cardiomyocyte injury caused by H/R and myocardial injury caused by I/R. Furthermore, AU suppressed the production of reactive oxygen species and inflammatory molecules (TNF-alpha, IL-1β, and IL-6) and proteins associated with cell death (caspase-3 and Bax), while enhancing the levels of anti-inflammatory agents (IL-10) and the anti-apoptotic protein Bcl-2.AU mechanistically affected the phosphorylation of STAT3 at the Ser727 site and Tyr705 following H/R by modulating the signaling pathway involving signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB)/high mobility group box 1 (HMGB1), while also suppressing the nuclear translocation of NF-κB p65 and HMGB1 exonucleation. In conclusion, the use of AU treatment might offer protection against myocardial infarction and injury by reducing oxidative stress, suppressing apoptosis, and mitigating inflammation. The regulation of the STAT3/NF-κB/HMGB-1 pathway may contribute to this phenomenon by affecting STAT3 phosphorylation and controlling NF-κB and HMGB-1 translocation. Contributes to identifying possible objectives for myocardial ischemia/reperfusion damage.