Cibele Rodrigues Toledo1, Vinicius Viana Pereira2, Lucienir Pains Duarte3, Grasiely Faria Sousa3, Armando Silva-Cunha2. 1. Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. ci.toledo02@gmail.com. 2. Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 3. Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Abstract
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.
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.