Sae-Kwang Ku1, Jeong Ah Kim, Jong-Sup Bae. 1. Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
Abstract
AIM AND OBJECTIVE: The nuclear DNA binding protein known as high-mobility group box 1 (HMGB1) acts as a late mediator of severe vascular inflammatory conditions, such as sepsis and septic shock. Piperlonguminine (PL), an important component of Piper longum fruit, is known to exhibit anti-hyperlipidemic, anti-platelet, and anti-melanogenesis activities. However, little is known about its effects on HMGB1-mediated inflammatory response. METHODS: We investigated the effects of PL on HMGB1-mediated inflammatory response by monitoring the effects of PL on lipopolysaccharide or cecal ligation and puncture (CLP)-mediated release of HMGB1, as well as on the modulation of HMGB1-mediated inflammatory responses. RESULTS: According to our data, PL caused inhibition of the release of HMGB1 and downregulation of HMGB1-dependent inflammatory responses in human endothelial cells. PL also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with PL reduced the CLP-induced release of HMGB1 and sepsis-related mortality. CONCLUSION: These results indicate that PL could be a candidate therapeutic agent for various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
AIM AND OBJECTIVE: The nuclear DNA binding protein known as high-mobility group box 1 (HMGB1) acts as a late mediator of severe vascular inflammatory conditions, such as sepsis and septic shock. Piperlonguminine (PL), an important component of Piper longum fruit, is known to exhibit anti-hyperlipidemic, anti-platelet, and anti-melanogenesis activities. However, little is known about its effects on HMGB1-mediated inflammatory response. METHODS: We investigated the effects of PL on HMGB1-mediated inflammatory response by monitoring the effects of PL on lipopolysaccharide or cecal ligation and puncture (CLP)-mediated release of HMGB1, as well as on the modulation of HMGB1-mediated inflammatory responses. RESULTS: According to our data, PL caused inhibition of the release of HMGB1 and downregulation of HMGB1-dependent inflammatory responses in human endothelial cells. PL also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with PL reduced the CLP-induced release of HMGB1 and sepsis-related mortality. CONCLUSION: These results indicate that PL could be a candidate therapeutic agent for various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
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