* Department of Cosmetic Science and Technology, Seowon University, Cheongju 28674, Republic of Korea.
† Department of Biology Education, Seowon University, Cheongju 28674, Republic of Korea.
Am J Chin Med. 2017;45(6):1253-1271. doi: 10.1142/S0192415X17500690. Epub 2017 Aug 22.
Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of severe sepsis or septic shock. In this study, we examined the effects of SFN on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. The anti-inflammatory activities of SFN were monitored based on its effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of SFN were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice. SFN inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. SFN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with SFN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in vivo. Our results indicate that SFN is a possible therapeutic agent that can be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.
萝卜硫素（SFN）是十字花科蔬菜如西兰花和白菜中存在的一种天然异硫氰酸盐，可有效预防癌症发生、糖尿病和炎症反应。抑制高迁移率族蛋白 B1（HMGB1）并恢复内皮完整性，在严重脓毒症或脓毒性休克的治疗中成为一种有吸引力的治疗策略。在这项研究中，我们研究了 SFN 在小鼠脓毒症模型中对 HMGB1 介导的脓毒症反应和存活率的影响。SFN 的抗炎活性通过其对脂多糖（LPS）或盲肠结扎和穿刺（CLP）介导的 HMGB1 释放的影响来监测。SFN 的抗菌活性通过测量 HMGB1 激活的人脐静脉内皮细胞（HUVEC）和小鼠中的通透性、白细胞黏附和迁移以及促炎蛋白的激活来确定。SFN 抑制 HMGB1 的释放，并下调人内皮细胞中 HMGB1 依赖性炎症反应。SFN 还抑制 HMGB1 介导的小鼠通透性增加和白细胞迁移。此外，SFN 治疗可减少 CLP 诱导的 HMGB1 释放以及体内脓毒症相关死亡率和肺损伤。我们的研究结果表明，SFN 是一种可能的治疗剂，可通过抑制 HMGB1 信号通路用于治疗各种严重的血管炎症性疾病。
