Anti-angiogenic activity and safety of intraocular application of triterpenes

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.