title: Paeoniflorin attenuates cardiac dysfunction in endotoxemic mice via the inhibition of nuclear factor-κB.
abstract: The impaired cardiac function caused by reduced myocardial contractility is a typical manifestation of sepsis/septic shock. Paeoniflorin (Pae) has reportedly exhibited anti-inflammatory effect and protection against LPS-induced cardiac dysfunction in mice, but the molecular mechanism is still not fully understood. This study was designed to investigate the protective effects of Pae on lipopolysaccharide (LPS)-induced septic cardiac dysfunction and inflammation response in mice. Mice were intraperitoneal injection with Pae (15mg/kg) for 3d before the LPS challenge (10mg/kg, i.p.). Pae significantly protected against LPS-induced cardiac dysfunction and damage. Pae decreased production of inflammatory cytokines, e.g., TNF-α, IL-1β, IL-6, IL-12, MCP-1, IFN-γ, and inducible nitric oxide synthase (iNOS), in the heart of LPS-treated mice. Furthermore, Pae prevented NF-κB activation in endotoxemic mice. Pae pretreatment preserved the level of phospho-Akt. Pae effectively improved cardiac function during endotoxemia in mice. This action is attributed to Pae-induced reduction of inflammatory cytokine release and NF-κB activation, which possibly occurred via the activation PI3K/Akt signaling.
authors.affiliation: Department of Emergency internal medicine, The General Hospital of Tianjin Medical University, Heping District, Tianjin 300052, PR China. Electronic address: ZhaiJianhua2015@163.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhai
authors.affiliation: Department of otorhinolaryngology, The General Hospital of Tianjin Medical University, Heping District, Tianjin 300052, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019210:Troponin I / Q000097:blood; D016276:Ventricular Function / Q000187:drug effects; D006027:Glycosides
chemical_list: D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D016207:Cytokines; D005960:Glucosides; D018836:Inflammation Mediators; D007770:L-Lactate Dehydrogenase; D008070:Lipopolysaccharides; D039821:Monoterpenes; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D019210:Troponin I; C015423:peoniflorin; D006027:Glycosides
keywords: Cardiac dysfunction; Endotoxin; Paeoniflorin; Phosphatidlyinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway