Bárbara Verena Dias Galvão1, Carlos Fernando Araujo-Lima2, Mônica Cristine Pereira Dos Santos3, Mariana Pulmar Seljan3, Eduardo Kennedy Carrão-Dantas1, Claudia Alessandra Fortes Aiub4, Luiz Claudio Cameron5, Mariana Simões Larraz Ferreira6, Édira Castello Branco de Andrade Gonçalves3, Israel Felzenszwalb1. 1. Laboratory of Environmental Mutagenesis, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil. 2. Laboratory of Environmental Mutagenesis, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil; Laboratory of Cell Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. Electronic address: biomed.carlos@gmail.com. 3. Laboratory of Bioactives, Nutritional Biochemistry Core, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. 4. Genetics and Molecular Biology Department, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. 5. Genetics and Molecular Biology Department, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Protein Biochemistry, Center of Innovation in Mass Spectrometry, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. 6. Laboratory of Bioactives, Nutritional Biochemistry Core, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Protein Biochemistry, Center of Innovation in Mass Spectrometry, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel, known as Brazilian grape or jaboticaba, is widely used in Brazilian traditional medicine to treat infectious and inflammatory disorders. However, several aspects of its biological potential remain unclear, such as toxicity and effects on pathogenic protozoa. AIM OF THE STUDY: Investigate the phenolic composition, the in vitro and in silico toxicity profile, and the anti-Trypanosoma cruzi activity of the phenolics-enriched hydromethanolic extract of P. cauliflora leaf. MATERIAL AND METHODS: Phytochemical analysis was performed ultra-performance liquid chromatography-mass spectrometry (UPLC-MSE). Mutagenicity, genotoxicity and eukaryotic cytotoxicity was evaluated by Ames test, cytokinesis-block micronucleus and colorimetric assays, respectively, alongside with a computational prediction of the major compound's pharmacokinetics and toxicity. Anti-T. cruzi activity was investigated on T. cruzi bloodstream trypomastigotes. RESULTS: A total of 14 phenolic compounds were identified, including 11 flavonoids and 2 phenolic acids. No positive response regarding mutagenic potential was detected in Salmonella strains TA97, TA98, TA100, TA102, TA104, both in absence or presence of metabolic activation. The extract induced significant dose-response reduction on nuclear division indexes of HepG2 cells, suggesting cytostatic effects, with no micronuclei induction on cytokinesis-block micronucleus assay. Likewise, it also presented cytotoxic effects, inducing HepG2 and F C3H dose and time dependently cell death through cell membrane damage and more evidently by mitochondrial dysfunction. A dose-response curve of in vitro trypanocidal activity was observed against T. cruzi bloodstream trypomastigotes after 2 and 24 h of exposure. In silico predictions of most abundant compounds' structural alerts, pharmacokinetics and toxicity profile indicates a moderately feasible druglikeness profile and low toxicity for them, which is compatible with in vitro results. CONCLUSIONS: The present study demonstrated that P. cauliflora leaf extract is a potential source of antiparasitic bioactive compounds, however it presents cytotoxic effects in liver cell lines.
ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel, known as Brazilian grape or jaboticaba, is widely used in Brazilian traditional medicine to treat infectious and inflammatory disorders. However, several aspects of its biological potential remain unclear, such as toxicity and effects on pathogenic protozoa. AIM OF THE STUDY: Investigate the phenolic composition, the in vitro and in silico toxicity profile, and the anti-Trypanosoma cruzi activity of the phenolics-enriched hydromethanolic extract of P. cauliflora leaf. MATERIAL AND METHODS: Phytochemical analysis was performed ultra-performance liquid chromatography-mass spectrometry (UPLC-MSE). Mutagenicity, genotoxicity and eukaryotic cytotoxicity was evaluated by Ames test, cytokinesis-block micronucleus and colorimetric assays, respectively, alongside with a computational prediction of the major compound's pharmacokinetics and toxicity. Anti-T. cruzi activity was investigated on T. cruzi bloodstream trypomastigotes. RESULTS: A total of 14 phenolic compounds were identified, including 11 flavonoids and 2 phenolic acids. No positive response regarding mutagenic potential was detected in Salmonella strains TA97, TA98, TA100, TA102, TA104, both in absence or presence of metabolic activation. The extract induced significant dose-response reduction on nuclear division indexes of HepG2 cells, suggesting cytostatic effects, with no micronuclei induction on cytokinesis-block micronucleus assay. Likewise, it also presented cytotoxic effects, inducing HepG2 and F C3H dose and time dependently cell death through cell membrane damage and more evidently by mitochondrial dysfunction. A dose-response curve of in vitro trypanocidal activity was observed against T. cruzi bloodstream trypomastigotes after 2 and 24 h of exposure. In silico predictions of most abundant compounds' structural alerts, pharmacokinetics and toxicity profile indicates a moderately feasible druglikeness profile and low toxicity for them, which is compatible with in vitro results. CONCLUSIONS: The present study demonstrated that P. cauliflora leaf extract is a potential source of antiparasitic bioactive compounds, however it presents cytotoxic effects in liver cell lines.
Authors: Luana P Borba-Santos; Caroline Deckmann Nicoletti; Taissa Vila; Patricia Garcia Ferreira; Carlos Fernando Araújo-Lima; Bárbara Verena Dias Galvão; Israel Felzenszwalb; Wanderley de Souza; Fernando de Carvalho da Silva; Vitor Francisco Ferreira; Debora Omena Futuro; Sonia Rozental Journal: Braz J Microbiol Date: 2022-03-08 Impact factor: 2.214