Engineering Research Center of Modern Preparation Technology of TCM, Shanghai University of Traditional Chinese Medicine, Pudong, Shanghai, 201203, People's Republic of China.
Glycobiology. 2010 Jan;20(4):473-84. doi: 10.1093/glycob/cwp199. Epub 2009 Dec 15.
Ophiopogon japonicus is a traditional Chinese medicine used to treat cardiovascular disease. Recent studies have confirmed its beneficial properties, but not the mechanism of action. Herein, we investigate the anti-ischemic properties of a water-soluble beta-d-fructan (MDG-1) from Ophiopogon japonicus, and assess the cytoprotective and proangiogenic effects of MDG-1. MDG-1 protects cardiomyocyte and microvascular endothelial cells (HMEC-1) against oxygen glucose deprivation (OGD)-induced cell death, as well as protect myocardial cells from ischemia-induced death occurring after coronary artery ligation in rats. Meanwhile, MDG-1 stimulates the differentiation of HMEC-1 cells into capillary-like structures in vitro and functions as a chemoattractant in migration assays, and promotes neovascularization in ischemic myocardium. In addition, MDG-1 upregulates sphingosine kinase 1 and sphingosine-1-phosphate (S1P) receptor 1 expression. Both MDG-1 and S1P induce basic fibroblast growth factor (bFGF) expression in HMEC-1 cells. Further study revealed that both MDG-1 and S1P induce Akt and ERK phosphorylation in a dose- and time-dependent manner, an effect that is attenuated by pre-treatment with either the Akt inhibitor wortmannin or the ERK inhibitor PD98059, and MDG-1 can also induce eNOS phosphorylation and increases in production of NO. These data indicate that MDG-1 presented remarkable anti-ischemic activity and protects cardiomyocyte and HMEC-1 cells from ischemia-induced cell damage by inducing S1P1 and bFGF cytoprotective and proangiogenic effects via the S1P/bFGF/Akt/ERK/eNOS signaling pathway.
麦冬是一种传统的中药，用于治疗心血管疾病。最近的研究证实了其有益特性，但不清楚其作用机制。本文研究了麦冬中一种水溶性 β-D-呋喃果糖（MDG-1）的抗缺血特性，并评估了 MDG-1 的细胞保护和促血管生成作用。MDG-1 可保护心肌细胞和微血管内皮细胞（HMEC-1）免受氧葡萄糖剥夺（OGD）诱导的细胞死亡，还可保护大鼠冠状动脉结扎后缺血引起的心肌细胞死亡。同时，MDG-1 可刺激 HMEC-1 细胞在体外分化为毛细血管样结构，并在迁移实验中作为趋化因子发挥作用，促进缺血心肌中的新生血管形成。此外，MDG-1 上调鞘氨醇激酶 1 和鞘氨醇-1-磷酸（S1P）受体 1 的表达。MDG-1 和 S1P 均可诱导 HMEC-1 细胞中碱性成纤维细胞生长因子（bFGF）的表达。进一步的研究表明，MDG-1 和 S1P 均可剂量依赖性和时间依赖性地诱导 Akt 和 ERK 磷酸化，这种作用可被 Akt 抑制剂 wortmannin 或 ERK 抑制剂 PD98059 预处理所减弱，MDG-1 还可诱导 eNOS 磷酸化并增加 NO 的产生。这些数据表明，MDG-1 具有显著的抗缺血活性，通过 S1P/bFGF/Akt/ERK/eNOS 信号通路诱导 S1P1 和 bFGF 细胞保护和促血管生成作用，保护心肌细胞和 HMEC-1 细胞免受缺血引起的细胞损伤。
