Scholarlink

Background <p>Uvaol, a pentacyclic triterpene, exhibits antitumor activity; however, its effects on angiogenesis—a fundamental process for diabetic retinopathy, atherosclerosis, and cancer—remain unclear. This study aims to investigate the anti-angiogenic potential of uvaol and identify its molecular targets within the angiogenesis signaling cascade.</p> Objectives <p>To evaluate the anti-angiogenic properties of uvaol and elucidate its interactions with key angiogenic proteins.</p> Methods <p>In silico reverse molecular docking predicted uvaol’s binding affinity to angiogenesis-related proteins. EGFR and BRAF, which exhibited the strongest affinities, were selected for in vitro enzyme inhibition assays to confirm uvaol’s inhibitory activity. The chorioallantoic membrane (CAM) assay assessed uvaol’s anti-angiogenic effects in ovo. Additionally, SwissADME and Protox computational tools evaluated drug-likeness and predicted toxicity profiles.</p> Results <p>Uvaol demonstrated strong binding affinities to EGFR and BRAF with binding energies of − 9.6&#xa0;kcal/mol and − 8.1&#xa0;kcal/mol, respectively. Enzyme assays revealed significant inhibition of EGFR (IC<sub>50</sub> = 146.79&#xa0;µM; <i>p</i> &lt; 0.05) and moderate inhibition of BRAF (IC<sub>50</sub> &gt; 1000&#xa0;µM). The CAM assay showed significant reduction in vascular branching (IC<sub>50</sub> = 511.61&#xa0;µM) and junction formation (IC<sub>50</sub> = 501.93&#xa0;µM) compared to celecoxib (<i>p</i> &lt; 0.05). Uvaol complied with Lipinski’s and Veber’s drug-likeness criteria and exhibited a favorable toxicity profile with low predicted risks of organ toxicity and mutagenicity.</p> Conclusion <p>These findings suggest uvaol functions as a potential EGFR inhibitor with notable anti-angiogenic activity, supporting its therapeutic promise for angiogenesis-related diseases. Further mechanistic studies and in vivo validations are warranted to optimize pharmacokinetics and efficacy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Evaluation of the anti-angiogenic property of uvaol: in silico, in vitro, and in ovo approaches

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月15日

查看全文
  • Jibrielle L. Simpauco,
  • Junie B. Billones,
  • Ross D. Vasquez,
  • Agnes L. Llamasares-Castillo

摘要

Background

Uvaol, a pentacyclic triterpene, exhibits antitumor activity; however, its effects on angiogenesis—a fundamental process for diabetic retinopathy, atherosclerosis, and cancer—remain unclear. This study aims to investigate the anti-angiogenic potential of uvaol and identify its molecular targets within the angiogenesis signaling cascade.

Objectives

To evaluate the anti-angiogenic properties of uvaol and elucidate its interactions with key angiogenic proteins.

Methods

In silico reverse molecular docking predicted uvaol’s binding affinity to angiogenesis-related proteins. EGFR and BRAF, which exhibited the strongest affinities, were selected for in vitro enzyme inhibition assays to confirm uvaol’s inhibitory activity. The chorioallantoic membrane (CAM) assay assessed uvaol’s anti-angiogenic effects in ovo. Additionally, SwissADME and Protox computational tools evaluated drug-likeness and predicted toxicity profiles.

Results

Uvaol demonstrated strong binding affinities to EGFR and BRAF with binding energies of − 9.6 kcal/mol and − 8.1 kcal/mol, respectively. Enzyme assays revealed significant inhibition of EGFR (IC50 = 146.79 µM; p < 0.05) and moderate inhibition of BRAF (IC50 > 1000 µM). The CAM assay showed significant reduction in vascular branching (IC50 = 511.61 µM) and junction formation (IC50 = 501.93 µM) compared to celecoxib (p < 0.05). Uvaol complied with Lipinski’s and Veber’s drug-likeness criteria and exhibited a favorable toxicity profile with low predicted risks of organ toxicity and mutagenicity.

Conclusion

These findings suggest uvaol functions as a potential EGFR inhibitor with notable anti-angiogenic activity, supporting its therapeutic promise for angiogenesis-related diseases. Further mechanistic studies and in vivo validations are warranted to optimize pharmacokinetics and efficacy.