title: Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs.
abstract: 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.
authors.affiliation: BK21 Research Team for Developing Functional Health Food Materials, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Yang
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Song
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D024243:HMGB1 Protein / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D016328:NF-kappa B / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009828:Oleanolic Acid