Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice

Context: Astragaloside IV (ASI) is a major and active saponin derivative of Astragalus membranaceus (Fisch) Bge. The anti-inflammatory properties of ASI are important for its cardioprotective effects. However, the molecular mechanisms of the protective effect of ASI on lipopolysaccharide (LPS)-induced cardiac dysfunction is yet to be elucidated. Objective: This study was designed to investigate the therapeutic effects and possible mechanisms of ASI against LPS-induced septic cardiac dysfunction and inflammation in mice. Materials and methods: Mice were intraperitoneally injected with ASI (20 mg/kg) for 1 week before LPS challenge (10 mg/kg, i.p.). Left ventricular performance and morphology were analyzed using echocardiography 6 h after LPS induction. Activities of lactate dehydrogenase (LDH) in serum were measured and serum levels of cardiac troponin I (cTnI) were quantified by ELISA. Serum levels of tumor necrosis factor-a (TNF-a), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-1b were also quantified by ELISA. The protein expressions of NF-iB p65 and p-AKT in heart tissues were detected using Western blot analysis. Results: LPS administration deteriorated cardiac function and was attenuated by ASI pretreatment. ASI attenuated LPS-induced the increase of LDH and cTnI activities in mice. ASI also prevented NF-iB activation and subsequent myocardial inflammatory responses in endotoxemic mice. The effects of ASI were closely associated with the phosphatidylinositol- 3-kinase (PI3K/AKT) signaling pathway, as characterized by ASI-induced activation in phosphoAkt. ASI also extended the lifespan of toxemic mice. Conclusion: ASI significantly attenuated LPS-induced cardiac dysfunction and inflammatory mediator production by inhibiting NF-iB and activating PI3K/AKT signaling pathway