Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice. (3rd September 2015)

• Record Type: Journal Article
• Authors: Zhao, Peng; Wang, Ying; Zeng, Shan; Lu, Jie; Jiang, Tie-Min; Li, Yu-Ming
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 37:Number 5(2015:Oct.)
• Page Start: 428
• Page End: 433
• Publication Date: 2015-09-03
• Subjects: Astragaloside IV -- cardiac dysfunction -- NF-кB -- PI3K/Akt signaling -- sepsis/septic shock; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.3109/08923973.2015.1080266
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: 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-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-1β were also quantified by ELISA. The protein expressions of NF-кB 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-кB 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 phospho-Akt. ASI also extended the lifespan of toxemic mice. Conclusion : ASI significantly attenuated LPS-induced cardiac dysfunction and inflammatory mediator production by inhibiting NF-кB and activating PI3K/AKT signaling pathway.