Qishen granule (QSG) exerts cardioprotective effects by inhibiting NLRP3 inflammasome and pyroptosis in myocardial infarction rats

Qishen granule (QSG) is a traditional Chinese medicine formulation that is widely used in clinical practice for the treatment of myocardial infarction (MI), and its efficacy and safety have been well approved. However, the underlying mechanism by which QSG alleviates inflammation and cell pyroptosis remains unknown.The aim of this study was to clarify whether QSG ameliorated MI by inhibiting inflammasome activation and cell pyroptosis.In vivo, SD male rats were subjected to the left anterior ascending branch (LAD) ligation to construct MI model. And in vitro, OGD/R, ISO, Ang II and LPS-ATP were used to induce H9C2 cell injury. Cell viability and ROS were detected by CCK8 and DCFH-DA dye respectively. Western blots were applied to detect the expression of inflammasome-related proteins. Cell pyroptosis was evaluated by Calcein-AM/PI staining, Hoechst/PI staining and NT-GSDMD expression.QSG administration improved the cardiac function, as well as reduced inflammatory cell infiltration and collagen deposition. In H9C2 cells, OGD/R failed to induce inflammasome activation, while ISO, Ang II and LPS-ATP successfully induced inflammasome activation and cell pyroptosis, as evidenced by increased Caspase-1(P20) and NT-GSDMD. In LPS-ATP induced H9C2 model, ROS production and cell pyroptosis were suppressed when treated with QSG. Furthermore, QSG significantly decreased the protein levels of P65-NF-κB, NLRP3, ASC, Caspase-1 (P20), Cleaved IL-18, Cleaved IL-1β and NT-GSDMD.This study is the first to demonstrate that QSG has cardioprotective effects by inhibiting inflammasome activation and pyroptosis, which are considered as promising therapeutic targets for MI.