Department of Histology and Anatomy, College of Korean Medicine, Daegu Haany University, Gyeongsan-si 38610, Republic of Korea.
College of Pharmacy, Cell and Matrix Research Institute, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University (KNU), Daegu 41566, Republic of Korea.
Fitoterapia. 2019 Apr;134:447-453. doi: 10.1016/j.fitote.2019.03.022. Epub 2019 Mar 23.
Human endothelial cells-derived polyphosphate (PolyP) is one of the pro-inflammatory mediators as suggested by the previous reports. 2,2'-bipyridine containing natural products are generally accepted to have antimicrobial, cytotoxic and anti-inflammatory properties. This study was undertaken to investigate whether a 2,2'-bipyridine containing natural product, collismycins C, can modulate PolyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. After HUVECs or mice were activated with PolyP, cells or mice were post-treated with collismycins C. The anti-inflammatory activities of collismycins C were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in PolyP-activated HUVECs and mice. In addition, the beneficial effects of collismycins C on survival rate in PolyP-injected mice. Collismycins C inhibits PolyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, PolyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by collismycins C in HUVECs. These anti-inflammatory functions of collismycins C were confirmed in PolyP injected mice. In conclusion, based on the anti-inflammatory effects of collismycins C in PolyP-mediated septic response, collismycins C have therapeutic potential for various systemic inflammatory diseases.
先前的研究表明，人内皮细胞衍生的多聚磷酸盐（PolyP）是一种促炎介质。含 2,2'-联吡啶的天然产物通常被认为具有抗菌、细胞毒性和抗炎特性。本研究旨在探讨含 2,2'-联吡啶的天然产物 collismycins C 是否可以调节 PolyP 介导的人脐静脉内皮细胞（HUVEC）和小鼠的炎症反应。在 PolyP 激活 HUVEC 或小鼠后，用 collismycins C 对细胞或小鼠进行后处理。通过测量 PolyP 激活的 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 collismycins C 的抗炎活性。此外，还研究了 collismycins C 对 PolyP 注射小鼠存活率的有益影响。Collismycins C 抑制 PolyP 介导的屏障破坏、细胞黏附分子的表达以及白细胞与 HUVEC 的黏附和迁移。有趣的是，Collismycins C 抑制了 PolyP 在 HUVEC 中诱导的 NF-κB 激活以及 TNF-α 和 IL-6 的产生。这些 Collismycins C 的抗炎作用在 PolyP 注射小鼠中得到了证实。总之，基于 Collismycins C 在 PolyP 介导的败血症反应中的抗炎作用，Collismycins C 具有治疗各种全身性炎症性疾病的潜力。
