title: Tanshinone IIA attenuates cardiac dysfunction in endotoxin-induced septic mice via inhibition of NADPH oxidase 2-related signaling pathway.
abstract: Cardiac dysfunction is a critical event during sepsis/septic shock. Tanshinone IIA (TIIA), a compound extracted from herb medicine Danshen, has been shown possessing anti-inflammatory and anti-oxidative properties. It is possible, therefore, that treatment with TIIA may attenuate cardiac dysfunction during sepsis/septic shock through inhibition of inflammation. To test this possibility, we preadministrated C57BL/6 mice with TIIA prior to lipopolysaccharide (LPS) challenge. LPS significantly suppressed left ventricular function as evidenced by decreases in EF% and FS% in mice. However, TIIA pretreatment significantly attenuated cardiac dysfunction following LPS challenge. Furthermore, TIIA markedly attenuated the LPS-induced upregulation of circulating tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. Meanwhile, LPS challenge significantly increased myocardial reactive oxygen species (ROS) production, which was attenuated by TIIA. Moreover, TIIA treatment dramatically decreased the level of the Nox2, reduced phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) expression. In conclusion, TIIA effectively improves cardiac function during endotoxemia in mice. This is attributed to TIIA reducing inflammatory cytokines release and inhibiting the Nox2 signaling during endotoxemia.
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China. Electronic address: huanglibingys@126.com.
authors.forename: Libing
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Yudi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China. Electronic address: cuisuyang@163.com.
authors.forename: Suyang
authors.initials: S
authors.lastname: Cui
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D045784:Abietanes; D002316:Cardiotonic Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C021751:tanshinone; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases
keywords: Cardiac function; ERK; Lipopolysaccharide; NADPH oxidase; ROS; Sepsis