Ishii Masakazu, Nakahara Tatsuo, Araho Daisuke, Murakami Juri, Nishimura Masahiro
Department of Oral and Maxillofacial Prosthodontics, Kagoshima University Graduate school of Medical and Dental Science, Kagoshima 890-8544, Japan.
Maruzen Pharmaceuticals Co., Ltd., Hiroshima 729-3102, Japan.
Biomed Pharmacother. 2017 Jul;91:111-120. doi: 10.1016/j.biopha.2017.04.052. Epub 2017 Apr 24.
Glycolipids are the major constituent of the thylakoid membrane of higher plants and have a variety of biological and pharmacological activities. However, anti-inflammatory effects of glycolipids on vascular endothelial cells have not been elucidated. Here, we investigated the effect of glycolipids extracted from spinach on lipopolysaccharides (LPS)-induced endothelial inflammation and evaluated the underlying molecular mechanisms. Treatment with glycolipids from spinach had no cytotoxic effects on cultured human umbilical vein endothelial cells (HUVECs) and significantly blocked the expression of LPS-induced interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) in them. Glycolipids treatment also effectively suppressed monocyte adhesion to HUVECs. Treatment with glycolipids inhibited LPS-induced NF-κB phosphorylation and nuclear translocation. In addition, glycolipids treatment significantly promoted endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production in HUVECs. Furthermore, glycolipids treatment blocked LPS-induced inducible NOS (iNOS) expression in HUVECs. Pretreatment with a NOS inhibitor attenuated glycolipids-induced suppression of NF-κB activation and adhesion molecule expression, and abolished the glycolipids-mediated suppression of monocyte adhesion to HUVECs. These results indicate that glycolipids suppress LPS-induced vascular inflammation through attenuation of the NF-κB pathway by increasing NO production in endothelial cells. These findings suggest that glycolipids from spinach may have a potential therapeutic use for inflammatory vascular diseases.
糖脂是高等植物类囊体膜的主要成分，具有多种生物学和药理活性。然而，糖脂对血管内皮细胞的抗炎作用尚未阐明。在此，我们研究了从菠菜中提取的糖脂对脂多糖（LPS）诱导的内皮炎症的影响，并评估了其潜在的分子机制。菠菜糖脂处理对培养的人脐静脉内皮细胞（HUVECs）没有细胞毒性作用，并显著阻断了LPS诱导的白细胞介素（IL）-6、单核细胞趋化蛋白-1（MCP-1）、血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）在其中的表达。糖脂处理还有效抑制了单核细胞与HUVECs的黏附。糖脂处理抑制了LPS诱导的NF-κB磷酸化和核转位。此外，糖脂处理显著促进了HUVECs中内皮型一氧化氮合酶（eNOS）的激活和一氧化氮（NO）的产生。此外，糖脂处理阻断了LPS诱导的HUVECs中诱导型一氧化氮合酶（iNOS）的表达。用一氧化氮合酶抑制剂预处理减弱了糖脂诱导的NF-κB激活和黏附分子表达的抑制，并消除了糖脂介导的单核细胞与HUVECs黏附的抑制。这些结果表明，糖脂通过增加内皮细胞中NO的产生来减弱NF-κB途径，从而抑制LPS诱导的血管炎症。这些发现表明，菠菜中的糖脂可能对炎症性血管疾病具有潜在的治疗用途。
