Baicalin maintained redox balance and inhibited PI3K/AKT pathway via binding with AKT to ameliorated LPS induced cardiac injury

Purpose The aim of this study was to investigate the effects of baicalin on septic cardiomyopathy and to elucidate the underlying mechanisms involved. Specifically, this study sought to determine the effects of baicalin on septic cardiomyopathy induced by AC16 cells and LPS in C57BL/6J mice and its underlying mechanisms. Methods: Echocardiography, histological staining, immunoblotting, qPCR, ELISA, RNA-seq, network pharmacology and molecular docking were performed. Changes in cardiomyocytes after LPS injection in mice were observed. The targets of baicalein in septic cardiomyopathy were screened using molecular docking and molecular dynamics, and the pathway of baicalein action was further elucidated by using RNA-seq and network pharmacology. Results: LPS stimulation induced apoptosis, an inflammatory response and oxidative stress in cardiomyocytes. In vivo experiments revealed that baicalin treatment attenuated septic myocardial injury, as evidenced by enhanced cardiac functional parameters, preservation of myocardial structure, and reduced inflammatory/apoptotic responses, and RNA-seq analyses revealed that the Pi3k/AKT signaling pathway was activated after the administration of baicalin, which was verified both in vitro and in vivo; this indicated that the protective effects of baicalin were related to the findings in vitro and in vivo, suggesting that the protective effect of baicalin is related to the activation of the PI3K/AKT pathway. Molecular docking studies revealed that baicalin inhibited cardiomyocyte inflammation and cardiomyocyte apoptosis, thereby ameliorating sepsis-induced cardiac injury, which may be related to the PI3K/Akt pathway. Conclusion: Baicalin activates the PI3K/AKT pathway and protects against sepsis-induced cardiac injury by binding with AKT.