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Anti-angiogenic activity and safety of intraocular application of triterpenes

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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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais). We also acknowledge the donation of triterpenes from Núcleo de Estudos de Plantas Medicinais (NEPLAM) of Departamento de Química of UFMG.

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Authors and Affiliations

  1. Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Cibele Rodrigues Toledo, Vinicius Viana Pereira & Armando Silva-Cunha

  2. Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Lucienir Pains Duarte & Grasiely Faria Sousa

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  1. Cibele Rodrigues Toledo
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Correspondence to Cibele Rodrigues Toledo.

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Toledo, C.R., Pereira, V.V., Duarte, L.P. et al. Anti-angiogenic activity and safety of intraocular application of triterpenes. Doc Ophthalmol 143, 259–270 (2021). https://doi.org/10.1007/s10633-021-09841-z

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