Astragalus Polysaccharide Nanoparticles Alleviate Sepsis-Induced Myocardial Injury by Targeting the HSP90AA1/NLRP3 Signaling Pathway.

Abstract

PURPOSE: This study aimed to investigate the mechanisms by which Astragalus polysaccharide nanoparticles (APS-CS/TPP) protect against septic myocardial injury, addressing the limited understanding of how APS-CS/TPP specific signaling pathways in this condition. MATERIALS AND METHODS: Potential targets and pathways of Astragalus polysaccharide (APS) were initially predicted using network pharmacology, molecular docking, and microscale thermophoresis. APS-CS/TPP were prepared using an ion gel method with a chitosan derivative and characterized for formation, size, and surface charge. A murine model of septic myocardial injury was established by cecal ligation and puncture (CLP), and therapeutic outcomes were assessed via echocardiography, ELISA, histology, and Western blot. In vitro, H9c2 cells were stimulated with LPS and treated with APS-CS/TPP, with or without the HSP90AA1 inhibitor TAS-116, followed by evaluation of inflammatory markers and protein expression. RESULTS: APS showed high binding affinity to HSP90AA1. APS-CS/TPP improved survival and attenuated myocardial damage in septic mice. In vitro, they reduced levels of IL-1β, IL-6, and TNF-α, and downregulated HSP90AA1, NLRP3, caspase-1, and IL-1β. These effects were suppressed by TAS-116. CONCLUSION: APS-CS/TPP protect against septic myocardial injury by inhibiting the HSP90AA1/NLRP3 signaling pathway.