Role of chebulinic acid in angiogenesis

车布林酸在血管生成中的作用

基本信息

批准号：
9310354
负责人：
Sujit Basu
金额：
$ 38.5万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-15 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9310354
关键词：
Acids Adult Adverse effects Angiogenesis Inhibitors Angiogenic Factor Arthritis Asians Binding Blood Vessels Bone Marrow Bone Marrow Transplantation Cell Proliferation Cell physiology Chronic Disease Clinic Colon Carcinoma Disease Disease model Drug Targeting Endothelial Cells Experimental Designs Fruit Gelatinase B Goals Human Inflammatory Arthritis KDR gene Knowledge MMP9 gene Malignant Neoplasms Mediating Menstrual cycle Modeling Molecular Mus Myrobalans Nature Pathogenesis Pathogenicity Pathway interactions Patients Pharmacotherapy Physiologic Neovascularization Play Process Reporting Research Design Rheumatoid Arthritis Role Signal Pathway Stem cells Stream Synovial joint Tannic Acid Tissues Toxic effect Treatment Efficacy Treatment Protocols Tumor Angiogenesis VEGFA gene Vascular Diseases Vascular Permeabilities Wound Healing angiogenesis antiangiogenesis therapy colon cancer patients efficacy testing experimental study in vivo migration neovascularization novel pre-clinical prevent receptor tumor vasculogenesis

项目摘要

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.

尽管靶向血管内皮生长因子A（VEGF-A）介导血管生成可能是治疗肿瘤和关节炎，目前使用的抗VEGF-A代理人不仅昂贵，而且还具有严重的毒性排除了许多患者的用途。因此许多患者必须从这些严重副作用的治疗方案中取出，从而剥夺了他们的抗血管生成疗法的最佳益处。这是必要的确定新的廉价，无毒和有效的抗血管生成分子，这些分子可以在诊所安全地使用血管生成的疾病治疗一个重要的病原作用。我们在这项研究中将调查chebulinic Acid（CI）是否在桃果酱果实中通常发现的单宁蛋白可能是一种反 - 血管生成剂。 AIM 1将阐明CI抑制VEGF-A的机制介导的EC功能。在AIM 2中，将检查CI对血管生成的影响。最后，AIM 3将确定CI在抑制临床前抑制血管生成的疗效肿瘤和关节炎模型是因为肿瘤和关节炎是两种疾病已经建立了VEGF-A介导的新血管化。