Role of chebulinic acid in angiogenesis

虽然靶向血管内皮生长因子-A（VEGF-A）介导的 血管生成可以是治疗肿瘤的有效治疗方法， 关节炎时，目前使用的抗VEGF-A剂不仅昂贵，它们还具有 严重的毒性，使其无法在许多患者中使用。因此，许多患者 必须从这些严重副作用的治疗方案中剔除， 剥夺了他们抗血管生成治疗的最佳益处。这需要 鉴定新的廉价、无毒和有效的抗血管生成分子， 可以安全地用于临床治疗血管生成起作用的疾病， 重要的致病作用。我们在这项研究中将调查如果chebulinic酸（CI）， 一种在杨梅果实中常见且大量存在的单宁可以是这样一种抗- 血管生成剂目的1阐明CI抑制VEGF-A的机制 介导的EC功能。在目标2中，将检查CI对血管发生的影响。 最后，目标3将确定CI在临床前抑制血管生成中的功效。 肿瘤和关节炎模型，因为肿瘤和关节炎是两种疾病， VEGF-A介导的新生血管形成的研究已经建立。

Although targeting vascular endothelial growth factor-A (VEGF-A) mediated angiogenesis can be an effective therapeutic approach for the treatment of tumors and arthritis, the presently used anti-VEGF-A agents are not only expensive, they also have serious toxicities which preclude their uses in many patients. Therefore many patients have to be taken out of the treatment protocol for these serious side effects thereby, depriving them of the optimal benefits of anti-angiogenic therapy. This necessitates identifying newer inexpensive, non toxic and effective anti-angiogenic molecules which can be safely used in the clinics for the treatment of diseases where angiogenesis plays an important pathogenic role. We here in this study will investigate if chebulinic acid (CI), a tannin commonly and abundantly found in myrobalan fruits can be such an anti- angiogenic agent. Aim 1 will elucidate the mechanisms by which CI inhibits VEGF-A mediated EC functions. In Aim 2, the effects of CI on vasculogenesis will be examined. Finally, Aim 3 will determine the efficacy of CI in inhibiting angiogenesis in preclinical tumor and arthritis models because tumor and arthritis are two diseases where the role of VEGF-A mediated neovascularization have been established.