North American ginseng inhibits myocardial NOX2-ERK1/2 signaling and tumor necrosis factor-α expression in endotoxemia

Pharmacol Res. 2016 Sep:111:217-225. doi: 10.1016/j.phrs.2016.06.010. Epub 2016 Jun 16.


Sepsis is a systemic inflammatory response to infection with a high mortality but has no specific treatment despite decades of research. North American (NA) ginseng (Panax quinquefolius) is a popular natural health product with anti-oxidant and anti-inflammatory properties. The aim of the present study was to investigate the effects of NA ginseng on pro-inflammatory cytokine expression and cardiac function in endotoxemia, a model of sepsis. Mice were challenged with lipopolysaccharide (LPS) to induce endotoxemia. Myocardial expression of tumor necrosis factor-alpha (TNF-α), a major pro-inflammatory cytokine that causes cardiac dysfunction, was upregulated in mice with endotoxemia, which was accompanied by increases in NOX2 expression, superoxide generation and ERK1/2 phosphorylation. Notably, pretreatment with NA ginseng aqueous extract (50mg/kg/day, oral gavage) for 5days significantly inhibited NOX2 expression, superoxide generation, ERK1/2 phosphorylation and TNF-α expression in the heart during endotoxemia. Importantly, cardiac function and survival in endotoxemic mice were significantly improved. Additionally, pretreatment with ginseng extract inhibited superoxide generation, ERK1/2 phosphorylation and TNF-α expression induced by LPS in cultured cardiomyocytes. We conclude that NA ginseng inhibits myocardial NOX2-ERK1/2-TNF-α signaling pathway and improves cardiac function in endotoxemia, suggesting that NA ginseng may have the potential in the prevention of clinical sepsis.

Keywords: Lipopolysaccharide; NADPH oxidase; North American ginseng; Nox2; Sepsis; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Disease Models, Animal
  • Endotoxemia / chemically induced
  • Endotoxemia / drug therapy*
  • Endotoxemia / enzymology
  • Endotoxemia / physiopathology
  • Lipopolysaccharides
  • Male
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / pathology
  • NADPH Oxidase 2 / metabolism*
  • Panax / chemistry*
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Signal Transduction / drug effects*
  • Superoxides / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*
  • Ventricular Function, Left / drug effects


  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Superoxides
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3