title: Ameliorative Effect of Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) on HMGB1-Induced Septic Responses In Vitro and In Vivo.
abstract: 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. Aspalathin (Asp) and nothofagin (Not), which have been reported to have anti-oxidant activity, are the two major active dihydrochalcones found in green rooibos. In this study, we investigated the antiseptic effects and underlying mechanisms of Asp and Not against HMGB1-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of Asp and Not were determined by measuring permeability, monocyte adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. According to the results, Asp and Not 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, Asp and Not suppressed the production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) by HMGB1. Collectively, these results indicate that Asp and Not could be potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Republic of Korea.|BK21 Plus KNU Biomedical Convergence Program, Department of Biochemistry and Cell Biology, School of Medicine, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.affiliation: Division of Plant Biosciences, School of Applied BioSciences, College of Agriculture and Life Science, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Republic of Korea.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D036903:Aspalathus / Q000737:chemistry*; D047188:Chalcones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000009:adverse effects* / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D018805:Sepsis / Q000188:drug therapy* / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D047188:Chalcones; D024243:HMGB1 Protein; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C517016:aspalathin; C528728:nothofagin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Aspalathin; HMGB1; HUVEC; Inflammation; Nothofagin; Sepsis