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.

Public Health Relevance

Although anti-angiogenic drugs have shown promise in treatment of several diseases such as tumors and arthritis, but they are very expensive and have serious side effects. Therefore the goal of this proposal is to identify non toxic chebulinic acid, a natural compound abundantly found in myrobalan fruits as an effective anti-angiogenic agent for treatment of several disorders where angiogenesis plays an important role.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL131405-01A1
Application #
9176640
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gao, Yunling
Project Start
2016-08-15
Project End
2020-07-31
Budget Start
2016-08-15
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Ohio State University
Department
Pathology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210