Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses

• Published in: Inflammation research 2015-09, Vol.64 (9), p.733-746
• Main Authors: Yang, Eun-Ju, Ku, Sae-Kwang, Lee, Wonhwa, Song, Kyung-Sik, Bae, Jong-Sup
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Basidiomycota; Biomedical and Life Sciences; Biomedicine; Cell Adhesion - drug effects; Cell Movement - drug effects; Cells, Cultured; Cytokines - metabolism; Dermatology; E-Selectin - metabolism; Functional Food; Furans - pharmacology; Furans - therapeutic use; HMGB1 Protein - antagonists & inhibitors; HMGB1 Protein - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Immunology; Intercellular Adhesion Molecule-1 - metabolism; Lung - drug effects; Lung - pathology; Male; Mice, Inbred C57BL; Neurology; Neutrophils - drug effects; Neutrophils - physiology; Original Research Paper; Pharmacology/Toxicology; Polyozellus multiplex; Receptor for Advanced Glycation End Products - metabolism; Rheumatology; Sepsis - drug therapy; Sepsis - metabolism; Sepsis - pathology; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - metabolism; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-015-0856-3

Aim and objective The ubiquitous nuclear protein, high-mobility group box 1 (HMGB1), is released by activated macrophages and human umbilical vein endothelial cells (HUVECs) and functions as a late mediator of experimental sepsis. Polyozellin, which has been reported to have a variety of biological activities including antioxidant and anticancer activity, is the major active compound found in edible mushroom ( Polyozellus multiplex ). In this study, we investigated the antiseptic effects and underlying mechanisms of polyozellin against HMGB1-mediated septic responses in HUVECs and mice. Methods The anti-inflammatory activities of polyozellin were determined by measuring permeability, human neutrophil adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. Results According to the results, polyozellin effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, polyozellin suppressed the production of tumor necrosis factor-α and interleukin (IL)-6, and the activation of nuclear factor-κB and extracellular signal-regulated kinases 1/2 by HMGB1. Conclusion Collectively, these results indicate that P. multiplex containing polyozellin could be commercialized as functional food for preventing and treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.