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Effects of methanolic and aqueous Carica Papaya leaf extracts in transcriptional and miRNA-mediated regulation of fetal hemoglobin

2023-07Conference object Open access
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dc.contributor.authorJacques, Filipa
dc.contributor.authorCanteiro, Beatriz
dc.contributor.authorMendes, Maria
dc.contributor.authorDelgadinho, Mariana
dc.contributor.authorOliveira, Ketlyn
dc.contributor.authorGinete, Catarina
dc.contributor.authorGomes, Mário
dc.contributor.authorRibeiro, Edna
dc.contributor.authorBrito, Miguel
dc.contributor.authorGomes, Anita Q.
dc.date.accessioned2024-01-15T13:00:00Z
dc.date.available2024-01-15T13:00:00Z
dc.date.issued2023-07
dc.descriptionThis project was supported by Instituto Politécnico de Lisboa under the grant IDI&CA-IPL/2022/miRCa/ESTeSL and partially supported by FCT/MCTES (UIDB/05608/2020 and UIDP/05608/2020). The authors are grateful to Fernando Nunes for kindly providing the Carica Papaya leaves.pt_PT
dc.description.abstractSickle cell disease (SCD) is a genetic blood disorder caused by mutations in β-globin gene that affect the shape and transport of red blood cells in blood vessels, leading to various clinical complications. The pharmacological reactivation of Fetal Hemoglobin (HbF) through compounds such as Hydroxyurea (HU), is one of the available treatments, however, their safety concerns and expensive cost in low- and middle-income countries limit their use. In this context, it is essential to study novel HbF-inducing compounds that have scarcer adverse effects and can be widely available, such as Carica papaya extracts, a medicinal plant with anti-oxidant and anti-inflammatory properties. Therefore, the main aim of this work is to evaluate the effects of Carica Papaya leaf extracts (CPLE) in HbF reactivation. More specifically, we started by evaluating the effect of a methanolic CPLE extract in K562 cells (human immortalized myeloid leukemia cell line) at the proliferation rate and viability of the K562 cell line, compared to HU exposure. Subsequently, we analyzed the expression levels of HBG1 and HBG2 genes and that of their transcriptional and miRNA-mediated regulators. To achieve these goals, the K562 cell line was first exposed for 72 hours to CPMLE at 500 μg/mL and for 24 hours to EMFCP (0.5; 50, and 100 μg/mL) and to HU (25 μg/mL). After exposure to natural compounds, the effects of gene expression were quantified from total RNA using RT-qPCR. The results have indicated that cell proliferation and viability were affected by CPMLE only at the concentration of 500 μg/ml, with no effects being observed at the lower concentrations analyzed. Upon analysis of the expression levels of globins (HBA, HBB, HBG1, and HBG2), HbF regulatory genes (MYB, KLF1, BCL11A, and BGLT3), and miRNAs involved in the regulation of HbF we could observe more significant differences for the lower concentrations of extracts used, namely at the concentration of 0.5 μg/ml. As such we have decided to titrate down the concentration of methanolic leaf extracts used and test the exposure to aqueous leaf extracts which possess different biological compounds that might lead to a differential regulation of the genes under analysis. Our preliminary results have revealed that at the concentrations of 0,05 ug/ml; 0,5 ug/ml and 5 ug/ml the cell viability and proliferation rates were not affected either for methanolic or aqueous extracts. We are currently analyzing the expression levels of target and regulatory genes to determine the effect of both types of leaf extracts on regulators of HbF expression.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJacques F, Canteiro B, Delgadinho M, Oliveira K, Ginete C, Gomes M, Ribeiro E, Brito M, Gomes AQ, et al. Effects of methanolic and aqueous Carica Papaya leaf extracts in transcriptional and miRNA-mediated regulation of fetal hemoglobin. In: V H&TRC Bootcamp 2023, Caldas da Rainha, 10 de julho de 2023.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/16885
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationIDI&CA-IPL/2022/miRCa/ESTeSLpt_PT
dc.relation.publisherversionhttps://htrcenter.wordpress.com/2023/06/26/v-bootcamp-july-2023/pt_PT
dc.subjectCarica papayapt_PT
dc.subjectβ-hemoglobinopathiespt_PT
dc.subjectFetal hemoglobin reactivationpt_PT
dc.subjectGene expressionpt_PT
dc.subjectTranscriptional regulationpt_PT
dc.subjectmiRNA-mediated regulationpt_PT
dc.subjectIDI&CA-IPL/2022/miRCa/ESTeSLpt_PT
dc.subjectFCT_UIDB/05608/2020pt_PT
dc.subjectFCT_UIDP/05608/2020pt_PT
dc.titleEffects of methanolic and aqueous Carica Papaya leaf extracts in transcriptional and miRNA-mediated regulation of fetal hemoglobinpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceCaldas da Rainhapt_PT
person.familyNameNeves Delgadinho
person.familyNameHonrado Ginete
person.familyNameRibeiro
person.familyNameBrito
person.familyNameGomes
person.givenNameMariana Isabel
person.givenNameAna Catarina
person.givenNameEdna
person.givenNameMiguel
person.givenNameAnita
person.identifierCAJ-5082-2022
person.identifier.ciencia-id231E-02E3-D9A9
person.identifier.ciencia-id8715-F62E-1E0F
person.identifier.ciencia-idC414-CDF2-D35A
person.identifier.ciencia-id231F-F341-7E93
person.identifier.ciencia-id4B10-E015-52B7
person.identifier.orcid0000-0003-0586-9154
person.identifier.orcid0000-0002-2334-782X
person.identifier.orcid0000-0003-1316-7750
person.identifier.orcid0000-0001-6394-658X
person.identifier.orcid0000-0002-3348-0448
person.identifier.ridA-7970-2016
person.identifier.ridC-3580-2014
person.identifier.scopus-author-id35224551000
person.identifier.scopus-author-id7202386033
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
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