Protective effects of astragalus polysaccharide nanoparticles on septic cardiac dysfunction through inhibition of TLR4/NF-κB signaling pathway

Sepsis-induced myocardial dysfunction was the leading cause of morbidity and mortality in hospitalized patients and yet there were no effective therapies. With excessive released inflammatory mediators through the TLR4-trigger NF-κB signaling pathway being implicated as key players in sepsis-induced myocardial injury, we prepared astragalus polysaccharide (APS) nanoparticles as an TLR4-responsive drug for alleviating sepsis-induced myocardial injury. Firstly, treatment with APS nanoparticles in LPS-treated H9c2 cells to evaluate the direct effect demonstrated that this drug maintained the cell viability, cell morphology and exerted anti-apoptotic effects. Additionally, animal studies using cecal ligation and puncture (CLP) in C57BL/6 mice revealed that APS nanoparticles were much more efficacious in attenuating sepsis-induced myocardial injury by down-regulating the bacterial loads, inhibiting serum C-reactive protein (CRP), white blood cells (WBC) levels, alleviating myocardial histopathologic abnormalities, remarkably reducing the cardiac troponin I (cTnI). Moreover, APS nanoparticles significantly decreased the myocardial inflammatory cytokine expression and inhibited the activity of TLR4/NF-κB pathway. In conclusion, APS nanoparticles could protect the sepsis-induced cardiac dysfunction. The mechanism of the protective action of APS nanoparticles seems to involve its ability to reduce inflammatory response and to suppress TLR4/NF-κB pathway. This drug may be a potential candidate strategy for septic cardiac dysfunction treatment.