Tong Yunguang, Zhang Xiongwen, Zhao Weimin, Zhang Yixiang, Lang Jingyu, Shi Yuhua, Tan Wenfu, Li Meihong, Zhang Yongwei, Tong Linjiang, Lu He, Lin Liping, Ding Jian
Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, 555 Zu-chong-zhi Road, Shanghai 201203, PR China.
Eur J Pharmacol. 2004 Jun 28;494(2-3):101-9. doi: 10.1016/j.ejphar.2004.04.053.
The Chinese folk medicine Shiraia bambusicola has long been utilized in the treatment of rheumatoid arthritis, a disease in which angiogenesis plays an important role. We report here the isolation of the compound Shiraiachrome A from S. bambusicola and the demonstration of its anti-angiogenic properties. We found that Shiraiachrome A significantly inhibited the proliferation, migration, and tube formation of human microvascular endothelial cells (HMEC) in a dose-dependent manner, with average IC(50) values of 2.1+/-0.36, 1.97+/-0.44, and 1.65+/-0.59 microM, respectively. In addition, Shiraiachrome A inhibited the formation of new microvessels in a rat aorta culture model as well as in the chick embryo chorioallantoic membrane (CAM) assay. Investigation of the mechanism of action of Shiraiachrome A demonstrated that this compound suppressed the autophosphorylation of four receptor tyrosine kinases (RTKs), with IC(50) values ranging from 2.2 to 4.3 microM. These results suggest that Shiraiachrome A inhibits angiogenesis by blocking growth factor-stimulated autophosphorylation of RTKs. These findings also indicate that Shiraiachrome A may be a potent therapeutic agent for angiogenesis-related diseases such as cancer, rheumatoid arthritis, and diabetic retinopathy.
中国民间药物竹黄长期以来一直用于治疗类风湿性关节炎，血管生成在该疾病中起重要作用。我们在此报告从竹黄中分离出化合物竹黄菌素A及其抗血管生成特性的证明。我们发现竹黄菌素A以剂量依赖性方式显著抑制人微血管内皮细胞（HMEC）的增殖、迁移和管形成，平均IC(50)值分别为2.1±0.36、1.97±0.44和1.65±0.59微摩尔。此外，竹黄菌素A在大鼠主动脉培养模型以及鸡胚绒毛尿囊膜（CAM）试验中抑制新微血管的形成。对竹黄菌素A作用机制的研究表明，该化合物抑制四种受体酪氨酸激酶（RTK）的自磷酸化，IC(50)值范围为2.2至4.3微摩尔。这些结果表明竹黄菌素A通过阻断生长因子刺激的RTK自磷酸化来抑制血管生成。这些发现还表明竹黄菌素A可能是用于治疗诸如癌症、类风湿性关节炎和糖尿病性视网膜病变等血管生成相关疾病的有效治疗剂。
