Tsuneki Hiroshi, Ma En-Long, Kobayashi Shinjiro, Sekizaki Naoto, Maekawa Kouji, Sasaoka Toshiyasu, Wang Min-Wei, Kimura Ikuko
Department of Clinical Pharmacology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Eur J Pharmacol. 2005 Apr 11;512(2-3):105-15. doi: 10.1016/j.ejphar.2005.02.035.
Abnormal angiogenesis is implicated in various diseases including cancer and diabetic retinopathy. In this study, we examined the effect of beta-eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea rhizome, on angiogenesis in vitro and in vivo. Proliferation of porcine brain microvascular endothelial cells and human umbilical vein endothelial cells (HUVEC) was inhibited by beta-eudesmol (50-100 microM). It also inhibited the HUVEC migration stimulated by basic fibroblast growth factor (bFGF) and the tube formation by HUVEC in Matrigel. beta-eudesmol (100 microM) blocked the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 induced by bFGF or vascular endothelial growth factor. Furthermore, beta-eudesmol significantly inhibited angiogenesis in subcutaneously implanted Matrigel plugs in mice and in adjuvant-induced granuloma in mice. These results indicate that beta-eudesmol inhibits angiogenesis, at least in part, through the blockade of the ERK signaling pathway. We considered that beta-eudesmol may aid the development of drugs to treat angiogenic diseases.
异常血管生成与包括癌症和糖尿病视网膜病变在内的多种疾病有关。在本研究中，我们检测了从白术根茎中分离出的倍半萜醇β-桉叶醇对体内外血管生成的影响。β-桉叶醇（50 - 100微摩尔）抑制了猪脑微血管内皮细胞和人脐静脉内皮细胞（HUVEC）的增殖。它还抑制了碱性成纤维细胞生长因子（bFGF）刺激的HUVEC迁移以及HUVEC在基质胶中的管腔形成。β-桉叶醇（100微摩尔）阻断了bFGF或血管内皮生长因子诱导的细胞外信号调节激酶（ERK）1/2的磷酸化。此外，β-桉叶醇显著抑制了小鼠皮下植入的基质胶栓子中的血管生成以及佐剂诱导的小鼠肉芽肿中的血管生成。这些结果表明，β-桉叶醇至少部分通过阻断ERK信号通路来抑制血管生成。我们认为β-桉叶醇可能有助于开发治疗血管生成性疾病的药物。
