title: Inhibitory effects of kaempferol-3-O-sophoroside on HMGB1-mediated proinflammatory responses.
abstract: High mobility group box 1 (HMGB1) protein is secreted by activated cells of the innate immune system and/or released by injured tissues and necrotic cells; HMGB1 up-regulates proinflammatory cytokines in several inflammatory diseases. Kaempferol-3-O-sophoroside (KP) was isolated from the leaves of cultivated mountain ginseng. KP has antitumor, antioxidative, antiallergic and antidiabetic activities, but the effects of KP on HMGB1-mediated proinflammatory responses have not been studied. In this study, we monitored the effect of KP on the lipopolysaccharide (LPS)-mediated release of HMGB1 and the HMGB1-mediated modulation of proinflammatory responses in human endothelial cells. We found that KP potently inhibited the release of HMGB1 by LPS and inhibited LPS- or HMGB1-mediated barrier permeability and expression of cell adhesion molecules. Further studies revealed that KP inhibited cell surface receptor of HMGB1, toll-like receptor (TLR) 2/4, but not the receptor for advanced glycation end products (RAGE). Collectively, these results suggest that KP possesses anti-inflammatory responses against HMGB1-mediated proinflammatory responses, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.
authors.affiliation: Department of Herbal Medicinal Pharmacology, College of Herbal Bio-Industry, 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: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D044949:Kaempferols / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D024243:HMGB1 Protein; D044949:Kaempferols; D011956:Receptors, Cell Surface; C064309:kaempferol 3-O-sophoroside