Exportação concluída — 

Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Rabelo, Liviane Maria Alves
Orientador(a): Alencar, Nylane Maria Nunes de
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/81532
Resumo: Frutapin is a lectin with affinity for glucose/mannose found in the seeds of Artocarpus altilis (breadfruit) and shares structural similarity with artocarpin, which is known for its immunostimulatory and wound-healing properties. Given its low natural extraction yield, the expression of its recombinant form in Escherichia coli was standardized, thereby increasing its production and enabling studies on its pharmacological potential. This study aimed to investigate the recombinant form of frutapin (rFTP) for its wound-healing potential in vitro and in vivo by evaluating the viability of fibroblasts (L929), keratinocytes (HaCaT), and macrophages (RAW 264.7) using the resazurin assay, as well as nitric oxide production (Griess assay) and cytokines TNF-α, IL-1β, IL-6, and IL-10 (ELISA) in RAW 264.7 cell supernatants. Subsequently, rFTP (0.1%, 0.5%, and 1%) was incorporated into xyloglucan-based biomembranes and tested in excisional wounds in BALB/c mice (n = 6 animals/group), compared with untreated controls (sham) and biomembrane without the active compound. The animals were euthanized on days 3, 7, and 14 post-surgery. rFTP (0.15–1 mg/mL) increased the proliferation of L929 and HaCaT cells and modulated the inflammatory response in RAW 264.7 macrophages compared to the CTRL group, significantly enhancing proliferation and IL-10 production while reducing the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, both in the presence and absence of LPS. The xyloglucan biomembrane containing 0.1% rFTP accelerated wound contraction and reduced inflammatory cell infiltration on days 3 and 7. Moreover, epithelial thickness was significantly higher in the rFTP-treated groups (0.1%) compared to the sham and control groups, highlighting rFTP’s ability to stimulate tissue regeneration and extracellular matrix remodeling. Levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was considerably increased, suggesting that rFTP modulates inflammation. These results indicate that rFTP is a promising candidate for wound management by promoting inflammatory control and regenerative stimulation. Thus, this work encourages further studies to elucidate the specific molecular mechanisms of rFTP and to assess its efficacy and safety in clinical trials.
id UFC-7_1725d9348ffb2644fc47202673ad25de
oai_identifier_str oai:repositorio.ufc.br:riufc/81532
network_acronym_str UFC-7
network_name_str Repositório Institucional da Universidade Federal do Ceará (UFC)
repository_id_str
spelling Rabelo, Liviane Maria AlvesSousa, Felipe Domingos deAlencar, Nylane Maria Nunes de2025-07-11T11:47:26Z2025-07-11T11:47:26Z2025RABELO, Liviane Maria Alves. Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo, 2025. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://repositorio.ufc.br/handle/riufc/81532. Acesso em: 11 jul. 2025.http://repositorio.ufc.br/handle/riufc/81532Frutapin is a lectin with affinity for glucose/mannose found in the seeds of Artocarpus altilis (breadfruit) and shares structural similarity with artocarpin, which is known for its immunostimulatory and wound-healing properties. Given its low natural extraction yield, the expression of its recombinant form in Escherichia coli was standardized, thereby increasing its production and enabling studies on its pharmacological potential. This study aimed to investigate the recombinant form of frutapin (rFTP) for its wound-healing potential in vitro and in vivo by evaluating the viability of fibroblasts (L929), keratinocytes (HaCaT), and macrophages (RAW 264.7) using the resazurin assay, as well as nitric oxide production (Griess assay) and cytokines TNF-α, IL-1β, IL-6, and IL-10 (ELISA) in RAW 264.7 cell supernatants. Subsequently, rFTP (0.1%, 0.5%, and 1%) was incorporated into xyloglucan-based biomembranes and tested in excisional wounds in BALB/c mice (n = 6 animals/group), compared with untreated controls (sham) and biomembrane without the active compound. The animals were euthanized on days 3, 7, and 14 post-surgery. rFTP (0.15–1 mg/mL) increased the proliferation of L929 and HaCaT cells and modulated the inflammatory response in RAW 264.7 macrophages compared to the CTRL group, significantly enhancing proliferation and IL-10 production while reducing the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, both in the presence and absence of LPS. The xyloglucan biomembrane containing 0.1% rFTP accelerated wound contraction and reduced inflammatory cell infiltration on days 3 and 7. Moreover, epithelial thickness was significantly higher in the rFTP-treated groups (0.1%) compared to the sham and control groups, highlighting rFTP’s ability to stimulate tissue regeneration and extracellular matrix remodeling. Levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was considerably increased, suggesting that rFTP modulates inflammation. These results indicate that rFTP is a promising candidate for wound management by promoting inflammatory control and regenerative stimulation. Thus, this work encourages further studies to elucidate the specific molecular mechanisms of rFTP and to assess its efficacy and safety in clinical trials.A Frutapina é uma lectina com afinidade por glicose/manose presente em sementes de Artocapus altilis (fruta-pão) e apresenta semelhança estrutural com Artocarpina, conhecida por suas propriedades imunoestimulantes e cicatrizantes. Considerando seu baixo rendimento de extração natural, a expressão da sua forma recombinante em Escherichia coli foi padronizada, e, assim, aumentou sua produção, viabilizando estudos sobre seu potencial farmacológico. Este trabalho teve como objetivo a investigar a forma recombinante da frutapina (rFTP) quanto ao seu potencial cicatrizante in vitro e in vivo através da avaliação da viabilidade de Fibroblastos (L929), Queratinócitos (HaCaT) e Macrófagos (RAW 264.7) (resazurina), bem como a produção de Óxido Nítrico (Griess) e Citocinas TNF-a, IL-1b, IL-6 e IL-10 (Elisa) no sobrenatante da RAW 264.7. Em seguida, a rFTP (0,1%, 0,5% e 1%) foi incorporada em biomembranas de Xiloglucana e testada em feridas excisionais de camundongos BALB/c (n=6animais/grupo), comparando-se com os controles sem tratamento (Sham) e biomembrana, sem o ativo. Os animais foram eutanasiados após 3, 7 e 14 dias após a cirurgia. A rFTP (0,15 – 1mg/mL) aumentou a proliferação da L929, HaCaT, bem como modulou a resposta inflamatória da RAW 264.7, em comparação ao grupo CTRL, aumentando significativamente a proliferação e a produção da citocina anti-inflamatória IL-10 e reduzindo os níveis das citocinas pró-inflamatórias TNF-α e IL-6 e IL1β com e sem LPS. A biomembrana de xiloglucana contendo rFTP na concentração de 0,1% acelerou a contração das lesões e diminuiu o infiltrado inflamatório no 3º e 7º dia. Além disso, a espessura epitelial foi significativamente maior nos grupos tratados com rFTP (0,1%) em comparação aos grupos sham e controle, evidenciando a capacidade da rFTP de estimular a regeneração tecidual e estruturação da matriz extracelular. Os níveis de IL-1β, TNF-α e IL-6 foram reduzidos e houve um aumento considerável de IL-10, sugerindo que a rFTP modula inflamação. Esses resultados indicam que a rFTP é uma candidata promissora para o manejo de feridas através do controle inflamatório e estimulação regenerativa. Dessa forma, este trabalho impulsiona estudos adicionais para elucidar os mecanismos moleculares específicos da rFTP e avaliar sua eficácia e segurança em ensaios clínicos.Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivoEffect of the recombinant lectin r-frutapin from Artocarpus altilis on the wound healing process: in vitro and in vivo studiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisLectinas de PlantasProteínas RecombinantesReepitelizaçãoPlant LectinsRecombinant ProteinsRe-EpithelializationCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttps://orcid.org/0000-0001-5779-839Xhttp://lattes.cnpq.br/5481922226880838http://lattes.cnpq.br/9219662256316695http://lattes.cnpq.br/9542077634881460ORIGINAL2025_dis_lmarabelo.pdf2025_dis_lmarabelo.pdfapplication/pdf3456903http://repositorio.ufc.br/bitstream/riufc/81532/1/2025_dis_lmarabelo.pdf8ff4ef22e184b79b5d0e9d5f0da176b9MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/81532/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53riufc/815322025-07-11 08:48:31.022oai:repositorio.ufc.br:riufc/81532Tk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2025-07-11T11:48:31Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
dc.title.en.pt_BR.fl_str_mv Effect of the recombinant lectin r-frutapin from Artocarpus altilis on the wound healing process: in vitro and in vivo studies
title Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
spellingShingle Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
Rabelo, Liviane Maria Alves
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
Lectinas de Plantas
Proteínas Recombinantes
Reepitelização
Plant Lectins
Recombinant Proteins
Re-Epithelialization
title_short Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
title_full Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
title_fullStr Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
title_full_unstemmed Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
title_sort Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo
author Rabelo, Liviane Maria Alves
author_facet Rabelo, Liviane Maria Alves
author_role author
dc.contributor.co-advisor.none.fl_str_mv Sousa, Felipe Domingos de
dc.contributor.author.fl_str_mv Rabelo, Liviane Maria Alves
dc.contributor.advisor1.fl_str_mv Alencar, Nylane Maria Nunes de
contributor_str_mv Alencar, Nylane Maria Nunes de
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
Lectinas de Plantas
Proteínas Recombinantes
Reepitelização
Plant Lectins
Recombinant Proteins
Re-Epithelialization
dc.subject.ptbr.pt_BR.fl_str_mv Lectinas de Plantas
Proteínas Recombinantes
Reepitelização
dc.subject.en.pt_BR.fl_str_mv Plant Lectins
Recombinant Proteins
Re-Epithelialization
description Frutapin is a lectin with affinity for glucose/mannose found in the seeds of Artocarpus altilis (breadfruit) and shares structural similarity with artocarpin, which is known for its immunostimulatory and wound-healing properties. Given its low natural extraction yield, the expression of its recombinant form in Escherichia coli was standardized, thereby increasing its production and enabling studies on its pharmacological potential. This study aimed to investigate the recombinant form of frutapin (rFTP) for its wound-healing potential in vitro and in vivo by evaluating the viability of fibroblasts (L929), keratinocytes (HaCaT), and macrophages (RAW 264.7) using the resazurin assay, as well as nitric oxide production (Griess assay) and cytokines TNF-α, IL-1β, IL-6, and IL-10 (ELISA) in RAW 264.7 cell supernatants. Subsequently, rFTP (0.1%, 0.5%, and 1%) was incorporated into xyloglucan-based biomembranes and tested in excisional wounds in BALB/c mice (n = 6 animals/group), compared with untreated controls (sham) and biomembrane without the active compound. The animals were euthanized on days 3, 7, and 14 post-surgery. rFTP (0.15–1 mg/mL) increased the proliferation of L929 and HaCaT cells and modulated the inflammatory response in RAW 264.7 macrophages compared to the CTRL group, significantly enhancing proliferation and IL-10 production while reducing the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, both in the presence and absence of LPS. The xyloglucan biomembrane containing 0.1% rFTP accelerated wound contraction and reduced inflammatory cell infiltration on days 3 and 7. Moreover, epithelial thickness was significantly higher in the rFTP-treated groups (0.1%) compared to the sham and control groups, highlighting rFTP’s ability to stimulate tissue regeneration and extracellular matrix remodeling. Levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was considerably increased, suggesting that rFTP modulates inflammation. These results indicate that rFTP is a promising candidate for wound management by promoting inflammatory control and regenerative stimulation. Thus, this work encourages further studies to elucidate the specific molecular mechanisms of rFTP and to assess its efficacy and safety in clinical trials.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-07-11T11:47:26Z
dc.date.available.fl_str_mv 2025-07-11T11:47:26Z
dc.date.issued.fl_str_mv 2025
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv RABELO, Liviane Maria Alves. Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo, 2025. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://repositorio.ufc.br/handle/riufc/81532. Acesso em: 11 jul. 2025.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/81532
identifier_str_mv RABELO, Liviane Maria Alves. Efeito da lectina recombinante r-frutapina de Artocarpus altilis sobre o processo de cicatrização: estudos in vitro e in vivo, 2025. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://repositorio.ufc.br/handle/riufc/81532. Acesso em: 11 jul. 2025.
url http://repositorio.ufc.br/handle/riufc/81532
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
bitstream.url.fl_str_mv http://repositorio.ufc.br/bitstream/riufc/81532/1/2025_dis_lmarabelo.pdf
http://repositorio.ufc.br/bitstream/riufc/81532/3/license.txt
bitstream.checksum.fl_str_mv 8ff4ef22e184b79b5d0e9d5f0da176b9
8a4605be74aa9ea9d79846c1fba20a33
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
_version_ 1847793179259043840