title: Vascular barrier protective effects of phlorotannins on HMGB1-mediated proinflammatory responses in vitro and in vivo.
abstract: The phlorotannins (phloroglucinol, eckol, and dieckol) are active compounds found in Eisenia bicyclis, and have been widely investigated for their antioxidant, anti-tumor, and anti-cancer activities. In this study, we investigated the protective effects of these phlorotannins against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice treated by high mobility group box 1 protein (HMGB1), and the signaling pathways involved. The protective activities of the phlorotannins were determined by measuring permeability, leukocyte adhesion and migration, and the activations of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that the phlorotannins inhibited; lipopolysaccharide (LPS)-induced HMGB1 release, HMGB1-mediated barrier disruption, the expressions of cell adhesion molecules (CAMs), and the adhesion/transendothelial migration of leukocytes to human endothelial cells. The phlorotannins also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that the hydroxyl groups on dieckol positively regulated these vascular barrier protective effects. Collectively, these results suggest that phloroglucinol, eckol, and dieckol protect vascular barrier integrity by inhibiting hyperpermeability, the expressions of CAMs, and the adhesion and migration of leukocytes, which confirms their potential usefulnesses for the treatment of vascular inflammatory diseases.
authors.affiliation: Department of Herbal Medicinal Pharmacology, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Taeho
authors.initials: T
authors.lastname: Lee
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002463:Cell Membrane Permeability; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004147:Dioxins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D024243:HMGB1 Protein / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D044423:Kelp / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010696:Phloroglucinol / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013634:Tannins / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D001572:Benzofurans; D015815:Cell Adhesion Molecules; D004147:Dioxins; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D013634:Tannins; D051197:Toll-Like Receptor 4; C503840:dieckol; C060311:eckol; D010696:Phloroglucinol