Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
Inflamm Res. 2014 May;63(5):369-79. doi: 10.1007/s00011-014-0708-6. Epub 2014 Jan 29.
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.
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.
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.
These results indicate that PL could be a candidate therapeutic agent for various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
高迁移率族蛋白 B1（HMGB1）是一种核 DNA 结合蛋白，作为严重血管炎症疾病（如败血症和感染性休克）的晚期介质。荜茇酰胺（PL）是荜茇果实的重要成分，已知具有抗高血脂、抗血小板和抗黑色素生成活性。然而，关于其对 HMGB1 介导的炎症反应的影响知之甚少。
我们通过监测 PL 对脂多糖或盲肠结扎和穿刺（CLP）介导的 HMGB1 释放以及对 HMGB1 介导的炎症反应的调节的影响，研究了 PL 对 HMGB1 介导的炎症反应的影响。
根据我们的数据，PL 导致人内皮细胞中 HMGB1 的释放受到抑制，并且 HMGB1 依赖性炎症反应受到下调。PL 还抑制了 HMGB1 介导的小鼠通透性增加和白细胞迁移。此外，PL 治疗可减少 CLP 诱导的 HMGB1 释放和与败血症相关的死亡率。
这些结果表明，PL 可通过抑制 HMGB1 信号通路成为各种严重血管炎症疾病的候选治疗药物。
