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Azadirachta indica A. Juss (neem) phenolic extract inhibits human B-lymphoblastoid cells growth via cell cycle arrest, apoptosis induction, and DNA damage

2023-08-29Journal article Open access
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dc.contributor.authorSantos, Klebson Silva
dc.contributor.authorCosta, Carla
dc.contributor.authorBessa, Maria João
dc.contributor.authorTeixeira, João Paulo
dc.contributor.authorMuniz, Ana Veruska Cruz da Silva
dc.contributor.authorPadilha, Francine Ferreira
dc.contributor.authorDariva, Cláudio
dc.contributor.authorOliveira, Maria Beatriz Pinto Prior
dc.date.accessioned2024-02-01T13:16:03Z
dc.date.available2024-02-01T13:16:03Z
dc.date.issued2023-08-29
dc.description.abstractAim: As far as is known, the pharmaceutical effects of neem on human B-lymphoblastoid (TK6) cells have not been studied until now. Hence, the present study aimed to obtain neem phenolic extracts for inhibits the proliferation of TK6 cells and explore some possible underlying mechanisms involved in these effects. Methods: Hexane extract (HE) was obtained in the first step. After that, the residual hexane was removed from the neem. The dried neem sample was used in a new extraction for obtaining the ethyl acetate extract (EAE). Total phenolic compounds (TPC) and total flavonoid contents (TFC) were determined by spectrophotometric methods. Lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to evaluate the cytotoxicity in TK6 cells. The stop at G0/G1 cell cycle and inducing apoptosis in the TK6 cells were analyzed by flow cytometry. For deoxyribonucleic acid (DNA) damage evaluation, the alkaline comet test was used. Results: The higher TFC (65.50 mg/g of extract ± 1.17 mg/g of extract) and TPC (52.08 mg of extract ± 0.88 mg of extract) were obtained in EAE compared to HE that was obtained TFC of 14.61 mg/g of extract ± 0.60 mg/g of extract and TPC of 3.20 mg/g of extract ± 1.20 mg/g of extract. EAE was more significantly cytotoxic to TK6 cells than HE. The apoptosis induction was higher after exposure to 15.0 µg/mL of EAE (11.29%) in comparison to 15.0 µg/mL of HE (2.52%). The G0/G1 phase increased from 72% negative control (NC) to 83% after treatment with neem extracts (15 µg/mL). Neem extracts were also able to cause DNA strand breaks in TK6 cells. Conclusions: The extraction residue from neem leaf after hexane extraction is a source important of cytotoxic and genotoxic molecules against TK6 cells, the results also can suggest that the toxic effects in TK6 cells can be provided most likely due to the presence of high content of TPC from neem extracts.pt_PT
dc.description.sponsorshipThe CAPES (Coordination for the Improvement of Higher Education Personnel), Program Sandwich Abroad (Process: PDSE 99999.003409/15-5) provided funding for Klebson Silva Santos’ financial support and scholarship in Portugal. This study also was funded by CNPq (National Council for Scientific and Technological Development), and FAPITEC/SE (Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe). The study also was carried out with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020 and the project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265. This work was also supported by the UIDB/50006/2020 project, funded by FCT/MCTES (Portugal, through national funds); SYSTEMIC “an integrated approach to the challenge of sustainable food systems: adaptive and mitigatory strategies to address climate change and malnutrition”, a Knowledge hub on Nutrition and Food Security, funded by FWO, INRA, BLE, MIPAAF, IZM, RCN, FCT and AEI in a joint action of JPI HDHL, JPI-OCEANS, and FACCE-JPI launched in 2019 under the ERA-NET ERA-HDHL [696295].pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationExplor Foods Foodomics. 2023 Ago 29;1:130–142 doi: https://doi.org/10.37349/eff.2023.00011pt_PT
dc.identifier.doi10.37349/eff.2023.00011pt_PT
dc.identifier.eissn2837-9020
dc.identifier.urihttp://hdl.handle.net/10400.18/9013
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOpen Exploration Publishingpt_PT
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relationERA-NET Biomarkers for Nutrition and Health implementing the JPI HDHL objectives
dc.relation.publisherversionhttps://www.explorationpub.com/Journals/eff/Article/101011pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectMedicinal Plantpt_PT
dc.subjectBioactive Extractspt_PT
dc.subjectSequential Pressurized Fluidspt_PT
dc.subjectAntiproliferative Effectpt_PT
dc.subjectHuman B-lymphoblastoid Cellspt_PT
dc.subjectToxicologiapt_PT
dc.titleAzadirachta indica A. Juss (neem) phenolic extract inhibits human B-lymphoblastoid cells growth via cell cycle arrest, apoptosis induction, and DNA damagept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardTitleERA-NET Biomarkers for Nutrition and Health implementing the JPI HDHL objectives
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F50006%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/696295/EU
oaire.citation.endPage142pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage130pt_PT
oaire.citation.titleExploration of Foods and Foodomicspt_PT
oaire.citation.volume1pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamH2020
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.embargofctAcesso de acordo com a política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication88a5471f-2a0b-4849-a7b8-8e19595642e2
relation.isProjectOfPublicationeccce5f3-585c-46ef-9277-7db5962d45f7
relation.isProjectOfPublication208b467b-ba75-4c51-9190-3e3f47336f4b
relation.isProjectOfPublication.latestForDiscovery208b467b-ba75-4c51-9190-3e3f47336f4b

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