Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan, 712-715, South Korea.
Inflammation. 2014 Apr;37(2):338-48. doi: 10.1007/s10753-013-9745-5.
High mobility group box 1 (HMGB1) acts as a late mediator of vascular inflammatory conditions. Pellitorine (PT), an active amide compound from Asarum sieboldii, is known to possess antibacterial and anticancer properties. In this study, we investigated the anti-septic effects of PT against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by HMGB1 and the associated signaling pathways. According to our findings, treatment with PT resulted in inhibited release of HMGB1, down-regulation of HMGB1-dependent inflammatory responses in HUVECs, and inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with PT resulted in reduced cecal ligation and puncture (CLP)-induced release of HMGB1 and sepsis-related mortality. PT suppressed the production of tumor necrosis factor-α and interleukin 6 and the activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate the potential of PT as a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
高迁移率族蛋白 B1（HMGB1）作为血管炎症状态的晚期介质发挥作用。胡椒碱（PT）是细辛中的一种活性酰胺化合物，已知具有抗菌和抗癌特性。在这项研究中，我们研究了 PT 对 HMGB1 诱导的人脐静脉内皮细胞（HUVEC）中促炎反应的抗败血症作用及其相关信号通路。根据我们的研究结果，PT 处理可抑制 HMGB1 的释放，下调 HUVEC 中 HMGB1 依赖性炎症反应，并抑制 HMGB1 介导的小鼠通透性增加和白细胞迁移。此外，PT 处理可减少盲肠结扎和穿刺（CLP）诱导的 HMGB1 释放和与败血症相关的死亡率。PT 抑制 HMGB1 诱导的肿瘤坏死因子-α和白细胞介素 6 的产生以及核因子-κB 和细胞外调节激酶 1/2 的激活。总之，这些结果表明 PT 作为一种候选治疗剂，通过抑制 HMGB1 信号通路，具有治疗各种严重血管炎症疾病的潜力。
