Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs

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• 作者：Eun-Ju Yang^a ; ¹ ; Wonhwa Lee^b ; ^c ; ¹ ; Sae-Kwang Ku^d ; ¹ ; Kyung-Sik Song^c ; Jong-Sup Bae^c ; ^{baejs@knu.ac.kr}
• 关键词：Oleanolic acid ; Barrier integrity ; LPS ; HMGB1
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：May, 2012
• 卷：50
• 期：5
• 页码：1288-1294
• 文件大小：654 K

摘要

As a late mediator of inflammation, high mobility group box 1 (HMGB1) protein up-regulates pro-inflammatory cytokines in several inflammatory diseases. Further, high plasma levels of HMGB1 correlate with poor prognosis and increased mortality in patients with severe inflammation. Oleanolic acid (OA), a triterpenoid known for its anti-inflammatory and anti-cancer properties, is commonly present in several medicinal plants but the effects of OA on HMGB1-mediated pro-inflammatory responses of human endothelial cells is not well-studied. In this study, we investigated this question by monitoring the effect of OA on lipopolysaccharide (LPS)-mediated release of HMGB1 and the HMGB1-mediated modulation of inflammatory responses in human umbilical vein endothelial cells (HUVECs). OA potently inhibited the release of HMGB1 by HUVECs as well as down-regulated HMGB1-dependent adhesion and migration of the monocytic cell line THP-1 to activated HUVECs. OA also down-regulated the cell surface expression of the receptor of HMGB1, thereby inhibiting HMGB1-dependent pro-inflammatory responses by inhibiting activation of nuclear factor-魏B (NF-魏B) and production of tumor necrosis factor-伪 (TNF-伪) by HMGB1. Given these results, OA showed anti-inflammatory activities and could be a candidate as a therapeutic agent for various inflammatory diseases through the inhibition of the HMGB1 signaling pathway.