Abstract
Solidagenone, a labdane diterpene isolated from inflorescences of Solidago chilensis Meyen, Asteraceae, was investigated for its anti-inflammatory and anti-asthmatic action. Allergic pleurisy and allergic lung inflammation assays were performed at doses of 1, 10, 50, and 100 mg/kg in ovalbumin-sensitized mice. In vitro cytotoxicity was performed, using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] MTT assay in a murine J774A1 macrophage cell line and human blood cells at concentrations of 0.1–100 µg/ml, as well as genotoxicity using the comet assay. In addition, in silico predictions were performed using ADMET Predictor TM software to predict absorption, distribution, metabolism, excretion, and toxicity. This study showed the anti-inflammatory activity and the possibility of an anti-asthmatic action of solidagenone at a concentration of 6 mg considering calculations for adult humans. Furthermore, it was possible to assess toxicity in vitro under the conditions performed and compare it with the in silico predictions.
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Acknowledgements
The authors appreciate Dr. Ana Paula dos Santos Matos from UFRJ and Dr. Ludmila Rosa Bergsten Torralba from Fiocruz for their help in organizing some experimental data.
Funding
This paper was financially supported by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ), INOVA Fiocruz program, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (PROEP Farmanguinhos). This work was supported by the FAPERJ by Edital Cientista do Nosso Estado 2020 (CNE: E-26/201.077/2021) and Edital Apoio aos Programas e Cursos de Pós-Graduação Stricto Sensu do Estado do Rio de Janeiro 2020 (E-26/210.136/2021).
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DCDXPL: designed the study, performed experiments, analyzed results, and wrote the manuscript; TMB, FKF, TRC, TRM, AMTS, BAV, and TBO: performed experiments and analyzed results; DAG and RSO: proofread and edited the work; ALV, SSV, and ERJr supervised the work and conceptualized the study. All authors have read, reviewed, and approved the manuscript.
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This research project involving the use of human blood samples was approved by the Committee on Ethics in Research with Human Beings of the National Institute of Infectious Diseases Evandro Chagas-INI/FIOCRUZ under Ethical Assessment Presentation Certificate number 52788721.5.0000.5262. All experimental procedures were performed in accordance with the Ethics Committee on the Use of Laboratory Animals of the Oswaldo Cruz Foundation under license LW-7/19, Protocol P9/18-5.
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Lopes, D.C.D.X.P., de Brito, T.M., Ferraris, F.K. et al. Investigation of the Anti-asthmatic Activity of Solidagenone, In Vitro Toxicity Versus In Silico Studies. Rev. Bras. Farmacogn. 34, 280–287 (2024). https://doi.org/10.1007/s43450-023-00479-3
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DOI: https://doi.org/10.1007/s43450-023-00479-3