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A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7

Introduction: Gibberellins (GA) are terpenoids that serve as important plant hormones by acting as growth and response modulators against injuries and parasitism. In this study, we investigated the in vitro anti-NF-κB, anti-Candida, and antioxidant activity of gibberellin A4 (GA4) and A7 (GA7) compo...

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Autores principales: Nani, Bruno Dias, Rosalen, Pedro Luiz, Lazarini, Josy Goldoni, de Cássia Orlandi Sardi, Janaína, Romário-Silva, Diego, de Araújo, Leonardo Pereira, dos Reis, Mateus Silva Beker, Breseghello, Isadora, Cunha, Thiago Mattar, de Alencar, Severino Matias, da Silveira, Nelson José Freitas, Franchin, Marcelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324930/
https://www.ncbi.nlm.nih.gov/pubmed/35890244
http://dx.doi.org/10.3390/pharmaceutics14071347
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author Nani, Bruno Dias
Rosalen, Pedro Luiz
Lazarini, Josy Goldoni
de Cássia Orlandi Sardi, Janaína
Romário-Silva, Diego
de Araújo, Leonardo Pereira
dos Reis, Mateus Silva Beker
Breseghello, Isadora
Cunha, Thiago Mattar
de Alencar, Severino Matias
da Silveira, Nelson José Freitas
Franchin, Marcelo
author_facet Nani, Bruno Dias
Rosalen, Pedro Luiz
Lazarini, Josy Goldoni
de Cássia Orlandi Sardi, Janaína
Romário-Silva, Diego
de Araújo, Leonardo Pereira
dos Reis, Mateus Silva Beker
Breseghello, Isadora
Cunha, Thiago Mattar
de Alencar, Severino Matias
da Silveira, Nelson José Freitas
Franchin, Marcelo
author_sort Nani, Bruno Dias
collection PubMed
description Introduction: Gibberellins (GA) are terpenoids that serve as important plant hormones by acting as growth and response modulators against injuries and parasitism. In this study, we investigated the in vitro anti-NF-κB, anti-Candida, and antioxidant activity of gibberellin A4 (GA4) and A7 (GA7) compounds, and further determined their toxicity in vivo. Methods: GA4 and GA7 in vitro toxicity was determined by MTT method, and nontoxic concentrations were then tested to evaluate the GA4 and GA7 anti-NF-κB activity in LPS-activated RAW-luc macrophage cell culture (luminescence assay). GA4 in silico anti-NF-κB activity was evaluated by molecular docking with the software “AutoDock Vina”, “MGLTools”, “Pymol”, and “LigPlot+”, based on data obtained from “The Uniprot database”, “Protein Data Bank”, and “PubChem database”. The GA4 and GA7 in vitro anti-Candida effects against Candida albicans (MYA 2876) were determined (MIC and MFC). GA7 was also evaluated regarding the viability of C. albicans preformed biofilm (microplate assay). In vitro antioxidant activity of GA4 and GA7 was evaluated against peroxyl radicals, superoxide anions, hypochlorous acid, and reactive nitrogen species. GA4 and GA7 in vivo toxicity was determined on the invertebrate Galleria mellonella larvae model. Results: Our data show that GA4 at 30 µM is nontoxic and capable of reducing 32% of the NF-κB activation on RAW-luc macrophages in vitro. In vitro results were confirmed via molecular docking assay (in silico), since GA4 presented binding affinity to NF-κB p65 and p50 subunits. GA7 did not present anti-NF-κB effects, but exhibited anti-Candida activity with low MIC (94 mM) and MFC (188 mM) values. GA7 also presented antibiofilm properties at 940 mM concentration. GA4 did not present anti-Candida effects. Moreover, GA4 and GA7 showed antioxidant activity against peroxyl radicals, but did not show scavenging activity against the other tested radicals. Both compounds did not affect the survival of G. mellonella larvae, even at extremely high doses (10 g/Kg). Conclusion: Our study provides preclinical evidence indicating that GA4 and GA7 have a favorable low toxicity profile. The study also points to GA4 and GA7 interference with the NF-κB via, anti-Candida activity, and a peroxyl radical scavenger, which we argue are relevant biological effects.
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spelling pubmed-93249302022-07-27 A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7 Nani, Bruno Dias Rosalen, Pedro Luiz Lazarini, Josy Goldoni de Cássia Orlandi Sardi, Janaína Romário-Silva, Diego de Araújo, Leonardo Pereira dos Reis, Mateus Silva Beker Breseghello, Isadora Cunha, Thiago Mattar de Alencar, Severino Matias da Silveira, Nelson José Freitas Franchin, Marcelo Pharmaceutics Article Introduction: Gibberellins (GA) are terpenoids that serve as important plant hormones by acting as growth and response modulators against injuries and parasitism. In this study, we investigated the in vitro anti-NF-κB, anti-Candida, and antioxidant activity of gibberellin A4 (GA4) and A7 (GA7) compounds, and further determined their toxicity in vivo. Methods: GA4 and GA7 in vitro toxicity was determined by MTT method, and nontoxic concentrations were then tested to evaluate the GA4 and GA7 anti-NF-κB activity in LPS-activated RAW-luc macrophage cell culture (luminescence assay). GA4 in silico anti-NF-κB activity was evaluated by molecular docking with the software “AutoDock Vina”, “MGLTools”, “Pymol”, and “LigPlot+”, based on data obtained from “The Uniprot database”, “Protein Data Bank”, and “PubChem database”. The GA4 and GA7 in vitro anti-Candida effects against Candida albicans (MYA 2876) were determined (MIC and MFC). GA7 was also evaluated regarding the viability of C. albicans preformed biofilm (microplate assay). In vitro antioxidant activity of GA4 and GA7 was evaluated against peroxyl radicals, superoxide anions, hypochlorous acid, and reactive nitrogen species. GA4 and GA7 in vivo toxicity was determined on the invertebrate Galleria mellonella larvae model. Results: Our data show that GA4 at 30 µM is nontoxic and capable of reducing 32% of the NF-κB activation on RAW-luc macrophages in vitro. In vitro results were confirmed via molecular docking assay (in silico), since GA4 presented binding affinity to NF-κB p65 and p50 subunits. GA7 did not present anti-NF-κB effects, but exhibited anti-Candida activity with low MIC (94 mM) and MFC (188 mM) values. GA7 also presented antibiofilm properties at 940 mM concentration. GA4 did not present anti-Candida effects. Moreover, GA4 and GA7 showed antioxidant activity against peroxyl radicals, but did not show scavenging activity against the other tested radicals. Both compounds did not affect the survival of G. mellonella larvae, even at extremely high doses (10 g/Kg). Conclusion: Our study provides preclinical evidence indicating that GA4 and GA7 have a favorable low toxicity profile. The study also points to GA4 and GA7 interference with the NF-κB via, anti-Candida activity, and a peroxyl radical scavenger, which we argue are relevant biological effects. MDPI 2022-06-25 /pmc/articles/PMC9324930/ /pubmed/35890244 http://dx.doi.org/10.3390/pharmaceutics14071347 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nani, Bruno Dias
Rosalen, Pedro Luiz
Lazarini, Josy Goldoni
de Cássia Orlandi Sardi, Janaína
Romário-Silva, Diego
de Araújo, Leonardo Pereira
dos Reis, Mateus Silva Beker
Breseghello, Isadora
Cunha, Thiago Mattar
de Alencar, Severino Matias
da Silveira, Nelson José Freitas
Franchin, Marcelo
A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7
title A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7
title_full A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7
title_fullStr A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7
title_full_unstemmed A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7
title_short A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7
title_sort study on the anti-nf-κb, anti-candida, and antioxidant activities of two natural plant hormones: gibberellin a4 and a7
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324930/
https://www.ncbi.nlm.nih.gov/pubmed/35890244
http://dx.doi.org/10.3390/pharmaceutics14071347
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