College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Republic of Korea.
BK21 Plus KNU Biomedical Convergence Program, Department of Biochemistry and Cell Biology, School of Medicine, Republic of Korea.
Am J Chin Med. 2015;43(5):991-1012. doi: 10.1142/S0192415X15500573. Epub 2015 Jul 30.
The ubiquitous nuclear protein, high mobility group box 1 (HMGB1), is released by activated macrophages and human umbilical vein endothelial cells (HUVECs) and functions as a late mediator of experimental sepsis. Aspalathin (Asp) and nothofagin (Not), which have been reported to have anti-oxidant activity, are the two major active dihydrochalcones found in green rooibos. In this study, we investigated the antiseptic effects and underlying mechanisms of Asp and Not against HMGB1-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of Asp and Not were determined by measuring permeability, monocyte adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. According to the results, Asp and Not effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, Asp and Not suppressed the production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) by HMGB1. Collectively, these results indicate that Asp and Not could be potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.
无处不在的核蛋白，高迁移率族蛋白 B1（HMGB1），由活化的巨噬细胞和人脐静脉内皮细胞（HUVEC）释放，并作为实验性败血症的晚期介质发挥作用。已报道具有抗氧化活性的 aspalathin（Asp）和 nothofagin（Not）是绿罗布斯塔中发现的两种主要的活性二氢查尔酮。在这项研究中，我们研究了 Asp 和 Not 对 HUVEC 和小鼠中 HMGB1 介导的败血症反应的杀菌作用及其潜在机制。通过测量 HMGB1 激活的 HUVEC 和小鼠中的通透性、单核细胞黏附和迁移以及促炎蛋白的激活，来确定 Asp 和 Not 的抗炎活性。结果表明，Asp 和 Not 可有效抑制脂多糖（LPS）诱导的 HMGB1 释放，并抑制 HMGB1 介导的败血症反应，如白细胞的高通透性、黏附和迁移，以及细胞黏附分子的表达。此外，Asp 和 Not 还抑制了肿瘤坏死因子α（TNF-α）和白细胞介素 6（IL-6）的产生，以及 HMGB1 对核因子-κB（NF-κB）和细胞外信号调节激酶 1 和 2（ERK1/2）的激活。综上所述，这些结果表明，Asp 和 Not 可能通过抑制 HMGB1 信号通路成为治疗各种严重血管炎症性疾病的潜在治疗剂。
