Toxicogenomic analysis of pharmacological active coumarins isolated from Calophyllum brasiliense.

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It is an important source of bioactive natural products like, for instance soulatrolide, and mammea type coumarins. Soulatrolide is a tetracyclic dipyranocoumarins and a potent inhibitor of HIV-1 reverse transcriptase and Mycobacterium tuberculosis. Mammea A/BA and A/BB coumarins, pure or as a mixture, are highly active against several leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. In the present work, a toxicogenomic analysis of Soulatrolide and Mammea A/BA + A/BB (3:1) mixture was performed in order to validate the toxicological potential of this type of compounds. Soulatrolide or mixture of mammea A/BA + A/BB (3:1) was administered orally to male mice (CD-1) at dose of 100 mg/kg/daily, for 1 week. After this time, mice were sacrificed, and RNA extracted from the liver of treated animals. Transcriptomic analysis was performed using Affymetrix Mouse Gene 1.0 ST Array. Robust microarray analysis (RMA) and two way ANOVA test revealed for mammea mixture treatment 46 genes upregulated and 72 downregulated genes; meanwhile, for soulatrolide 665 were upregulated and 1077 downregulated genes. Enrichment analysis for such genes revealed that in both type of treatments genetic expression were mainly involved in drug metabolism. Overall results indicate a safety profile. The microarray data complies with MIAME guidelines and are deposited in GEO under accession number GSE72755.", "claims": [{"id": "claim-method", "statement": "A two way ANOVA was performed to identify differentially expressed genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26697389", "locator": "sections[6] \"Microarray experiments and data acquisition processing\" paragraph 2", "quote": "A two way ANOVA was performed to identify differentially expressed genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data is deposited in GEO under accession number GSE72755: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72755.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26697389", "locator": "sections[2] \"Direct link to deposited data\" paragraph 2", "quote": "The data is deposited in GEO under accession number GSE72755: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72755."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper used robust multiarray analysis (RMA) normalization and two-way ANOVA to identify differentially expressed genes, and the source microarray data are available through GEO accession GSE72755.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26697389"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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