Molecular docking and in silico analysis of the pharmacokinetics, toxicological profile and differential gene expression of bioactive compounds from Cyrtopodium glutiniferum .

Autor:	Araujo NGR; Laboratory of Environmental Mutagenesis, Department of Biophysics and Biometry, IBRAG/UERJ (University of the State of Rio de Janeiro), 87 - Fundos, 4th floor, Vila Isabel, Rio de Janeiro, RJ 20551-030, Brazil., da Silva Junior FC; Toxicology Center, University of Saskatchewan, 44 Campus Dr, Saskatchewan S7N 5B3, Canada., Santos LVS; Laboratory of Environmental Mutagenesis, Department of Biophysics and Biometry, IBRAG/UERJ (University of the State of Rio de Janeiro), 87 - Fundos, 4th floor, Vila Isabel, Rio de Janeiro, RJ 20551-030, Brazil., Batistuzzo de Medeiros SR; Laboratory of Biology and Molecular Mutagenesis, Department of Biology, Center for Biosciences/UFRN (Federal University of Rio Grande do Norte), 3000 Av. Sen. Salgado Filho-Lagoa Nova, Natal, RN 59064-741, Brazil., Felzenszwalb I; Laboratory of Environmental Mutagenesis, Department of Biophysics and Biometry, IBRAG/UERJ (University of the State of Rio de Janeiro), 87 - Fundos, 4th floor, Vila Isabel, Rio de Janeiro, RJ 20551-030, Brazil., Araújo-Lima CF; Laboratory of Environmental Mutagenesis, Department of Biophysics and Biometry, IBRAG/UERJ (University of the State of Rio de Janeiro), 87 - Fundos, 4th floor, Vila Isabel, Rio de Janeiro, RJ 20551-030, Brazil.; Integrated Environmental Mutagenesis Laboratory, Federal University of Rio de Janeiro State (UNIRIO), R. Frei Caneca, 94 - Centro, Rio de Janeiro, RJ 20211-010, Brazil.
Jazyk:	angličtina
Zdroj:	Toxicology reports [Toxicol Rep] 2024 Nov 15; Vol. 13, pp. 101810. Date of Electronic Publication: 2024 Nov 15 (Print Publication: 2024).
DOI:	10.1016/j.toxrep.2024.101810
Abstrakt:	The genus Cyrtopodium , from the Orchidaceae family, is widely used for its therapeutic properties in the treatment of tuberculosis, abscesses, urinary infection, and colds. C. glutiniferum , one of the species of this genus, is endemic in Brazil and largely used in herbal medicine. Thus, it is of great interest to recognize its composition, the properties of the molecules found in it. This study aimed to perform the in silico analysis of the main compounds from C. glutiniferum , on the platforms pKCSM, SwissADME, LAZAR, CLC-pred, ToxTree, DIGEPred, STRING, and Cytoscape. Further than this, the molecular docking was performed. The compounds present in the aqueous extract of C. glutiniferum were identified by UHPLC-MS/MS, finding Arbutin, Caffeic acid 4-O-glucoside, and Dihydroformononetin as the three most abundant molecules. The evaluation of the gastrointestinal absorption of Dihydroformononetin is given as high, also managing to cross the blood-brain barrier, while Arbutin can only be absorbed by the gastrointestinal tract and Caffeic acid 4-O-glucoside had very low absorption. Further analysis showed that Arbutin and Dihydroformononetin are possible leading molecules for drug synthesis, according to the prediction. Toxicological aspects were analysed, and no adverse effects were noted, but there were divergences in the mutagenic prediction of Arbutin and Dihydroformononetin, having different results in the used platforms, demonstrating that a cautious analysis and data insertion is needed in these tools to optimize them. The analysis of the differentially expressed genes predicted that the compounds can regulate several genes, including some genes associated with carcinogenesis and inflammation. The Molecular docking analysis showed high binding affinities of the molecules with different proteins. Therefore, C. glutiniferum demonstrates the potential to be used as a phytotherapeutic. The same was given through the in silico analysis of the three compounds found in the orchid, that show good individual potential. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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