Inhibitory effects of kaempferol-3-O-sophoroside on HMGB1-mediated proinflammatory responses

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.