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

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• 作者：Yan Wu^a ; ^b ; ^d ; ^{ywu221@163.com" class="auth_mail" title="E-mail the corresponding author} ; Chaoyi Qin^c ; ^d ; Xiangru Lu^d ; Jocelyn Marchiori^e ; Qingping Feng^d ; ^{Qingping.Feng@schulich.uwo.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：North American ginseng ; TNF-α ; NADPH oxidase ; Nox2 ; Lipopolysaccharide ; Sepsis
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：111
• 期：Complete
• 页码：217-225
• 全文大小：1971 K

文摘

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 (50 mg/kg/day, oral gavage) for 5 days 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.