Purpose

Assessment of the anti-angiogenic activity and the safety of ophthalmic use of four pentacyclic triterpenes (friedelin, friedelinol, lupenone, and lupeol).

Methods

Triterpenes cytotoxicity (5–640 µmol L⁻¹) was examined in ARPE-19 cells by sulforhodamine B colorimetric method, and the anti-angiogenic activity (50–1000 µmol L⁻¹) was evaluated in the chorioallantoic membrane model. Full-field electroretinography and histological analysis were performed to evaluate intraocular effects of these four triterpenes (at 100 or 500 μmol L⁻¹) in eyes of Wistar rats, for 15 days.

Results

In the cytotoxicity assay, friedelin and friedelinol were not able to drastically reduce cell growth. A dose-dependent response was observed in groups exposed to lupeol or lupenone. During the chorioallantoic membrane assay, friedelinol at 500 μmol L⁻¹ reduced the vascularity in 26%; lupeol and lupenone showed promising anti-angiogenic activity, reducing three parameters: vascularized area (> 30%), number of junctions (> 20%), and vessel length (> 15%). According to the electroretinographic and histologic findings, triterpenes at 100 µmol L⁻¹ or lupenone at 500 µmol L⁻¹ did not induce any transient or permanent disturbance in retinal structure or functioning.

Conclusions

Triterpenes at 100 µmol L⁻¹ or lupenone at 500 µmol L⁻¹ were considered safe for potential ophthalmic use.

中文翻译：

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三萜类眼内应用的抗血管生成活性和安全性

目的

评估四种五环三萜（弗里德林、弗里德林醇、羽扇豆酮和羽扇豆醇）的抗血管生成活性和眼科使用的安全性。

方法

通过磺基罗丹明 B 比色法在 ARPE-19 细胞中检测三萜类化合物的细胞毒性（5-640 µmol L ^-1），并在绒毛膜尿囊膜模型中评估抗血管生成活性（50-1000 µmol L ^-1）。进行全视野视网膜电图和组织学分析以评估这四种三萜（100 或 500 μmol L ^-1）在 Wistar 大鼠眼中的眼内效应，持续 15 天。

结果

在细胞毒性试验中，弗里德林和弗里德林不能显着降低细胞生长。在暴露于羽扇豆醇或羽扇豆酮的组中观察到剂量依赖性反应。在绒毛膜尿囊膜试验中，500 μmol L ^{-1 的}弗里德林醇使血管分布减少了 26%；羽扇豆醇和羽扇豆酮显示出有希望的抗血管生成活性，减少了三个参数：血管化面积（> 30%）、连接点数（> 20%）和血管长度（> 15%）。根据视网膜电图和组织学结果，100 µmol L ^{-1 的}三萜或 500 µmol L ^{-1 的}羽扇豆酮不会引起视网膜结构或功能的任何暂时或永久性干扰。

结论

100 µmol L ^{-1 的}三萜或 500 µmol L ^{-1 的}羽扇豆酮被认为对于潜在的眼科使用是安全的。