Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs

• Published in: Food and chemical toxicology 2012-05, Vol.50 (5), p.1288-1294
• Main Authors: Yang, Eun-Ju, Lee, Wonhwa, Ku, Sae-Kwang, Song, Kyung-Sik, Bae, Jong-Sup
• Format: Article
• Language: English
• Subjects: anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; anticarcinogenic activity; Barrier integrity; Biological and medical sciences; Cell Adhesion - drug effects; Cell Line; Cell Movement - drug effects; Down-Regulation - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme-Linked Immunosorbent Assay; HMGB1; HMGB1 Protein - metabolism; HMGB1 Protein - physiology; human umbilical vein endothelial cells; Humans; inflammation; lipopolysaccharides; LPS; Magnetic Resonance Spectroscopy; Medical sciences; medicinal plants; monitoring; mortality; NF-kappa B - metabolism; Oleanolic acid; Oleanolic Acid - pharmacology; patients; prognosis; signal transduction; Toxicology; transcription factor NF-kappa B; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2012.02.026

► HMGB1 is pro-inflammatory cytokine as a late mediator of inflammation. ► Oleanolic acid (OA) was isolated from mistletoe (Viscum album) plant. ► OA inhibited LPS induced HMGB1 release. ► OA also inhibited and HMGB1-mediated inflammatory responses. 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-κB (NF-κB) and production of tumor necrosis factor-α (TNF-α) 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.