title: Barrier protective effects of rosmarinic acid on HMGB1-induced inflammatory responses in vitro and in vivo.
abstract: High mobility group box 1 (HMGB1) protein is a crucial cytokine that mediates response to infection, injury, and inflammation. Rosmarinic acid (RA) is an important component of the leaves of Perilla frutescens and has neuroprotective, anti-microbial, anti-oxidant, and anti-cancer effects but little is known of its effects on HMGB1-mediated inflammatory response. Here, we investigated this issue by monitoring the effects of RA on the lipopolysaccharide (LPS) or cecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated modulation of inflammatory responses. RA potently inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. RA also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. Furthermore, RA reduced CLP-induced HMGB1 release and sepsis-related mortality. Given these results, RA should be viewed as a candidate therapeutic agent for the treatment of various inflammatory diseases via inhibition of the HMGB1 signaling pathway.
authors.affiliation: BK21 Research Team for Developing Functional Health Food Materials, Kyungpook National University, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Yang
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
authors.forename: Taeho
authors.initials: T
authors.lastname: Lee
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Song
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002934:Cinnamates / Q000008:administration & dosage* / Q000737:chemistry; D053630:Depsides / Q000008:administration & dosage* / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D031344:Perilla frutescens / Q000737:chemistry; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D000097123:Rosmarinic Acid