Ameliorative effect of a rarely occurring C-methylrotenoid on HMGB1-induced septic responses in vitro and in vivo

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• 作者：Eun-Ju Yang¹ ; Wonhwa Lee¹ ; Kyung-Sik Song ; ^{kssong@knu.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; Jong-Sup Bae ; ^{baejs@knu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Abronia nana ; C-Methylrotenoid ; HMGB1 ; Sepsis ; Inflammation ; HUVEC
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：110-111
• 期：Complete
• 页码：58-70
• 全文大小：2674 K

文摘

The ubiquitous nuclear protein, high mobility group box-1 (HMGB1) functions as a late mediator of sepsis. A new rarely occurring C-methylrotenoid, named boeravinone X (comp class="boldFont">1), was isolated and identified from Abronia nana suspension cultures during our continuous works on the discovery of anti-septic natural products. Here, we investigated the antiseptic effects and underlying mechanisms of comp class="boldFont">1 against HMGB1-mediated septic responses. According to the results, comp class="boldFont">1 effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. And, comp class="boldFont">1 suppressed the production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) by HMGB1. Collectively, these results indicate that comp class="boldFont">1 could be potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.