title: Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  ASI significantly attenuated LPS-induced cardiac dysfunction and inflammatory mediator production by inhibiting NF-кB and activating PI3K/AKT signaling pathway.
authors.affiliation: a Graduate School of Medicine, Tianjin Medical University , Tianjin , China and.|b Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces , Tianjin , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: b Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces , Tianjin , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces , Tianjin , China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: b Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces , Tianjin , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: b Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces , Tianjin , China.
authors.forename: Tie-Min
authors.initials: TM
authors.lastname: Jiang
authors.affiliation: b Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces , Tianjin , China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D012503:Saponins; D051996:Transcription Factor RelA; D014315:Triterpenes; C052064:astragaloside A; D051058:Oncogene Protein v-akt
keywords: Astragaloside IV; NF-кB; PI3K/Akt signaling; cardiac dysfunction; sepsis/septic shock