Abstract
Assessment of the anti-angiogenic activity and the safety of ophthalmic use of four pentacyclic triterpenes (friedelin, friedelinol, lupenone, and lupeol). Triterpenes cytotoxicity (5-640µmol L-1) was examined in ARPE-19 cells by sulforhodamine B colorimetric method, and the anti-angiogenic activity (50-1000µmol 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 500μmol L-1) in eyes of Wistar rats, for 15days. 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 500μmol 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 100µmol L-1 or lupenone at 500µmol L-1 did not induce any transient or permanent disturbance in retinal structure or functioning. Triterpenes at 100µmol L-1 or lupenone at 500µmol L-1 were considered safe for potential ophthalmic use.
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