From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/ijms21144952 http://hdl.handle.net/11449/200775 |
Resumo: | Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases. |
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From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibersCutaneous wound healingLupeolNatural productSkin regenerationTriterpeneSkin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Morphology Institute of Biosciences São Paulo State University (UNESP)Department of Surgery and Veterinary Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University (UNESP)Department of Clinics Veterinary School of Veterinary Medicine and Animal Science São Paulo State University (UNESP)Kolling Institute of Medical Research The University of Sydney at Royal North Shore Hospital, St. LeonardDepartment of Pharmacy Federal University of São Francisco Valley (UNIVASF)Department of Morphology Institute of Biosciences São Paulo State University (UNESP)Department of Surgery and Veterinary Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University (UNESP)Department of Clinics Veterinary School of Veterinary Medicine and Animal Science São Paulo State University (UNESP)FAPESP: 2013/23340-1FAPESP: 2014/23247-4FAPESP: 2017/17600-1Universidade Estadual Paulista (Unesp)The University of Sydney at Royal North Shore HospitalFederal University of São Francisco Valley (UNIVASF)Beserra, Fernando Pereira [UNESP]Gushiken, Lucas Fernando Sérgio [UNESP]Vieira, Ana Júlia [UNESP]Bérgamo, Danilo Augusto [UNESP]Bérgamo, Patrícia Luísa [UNESP]de Souza, Mariana Oliveira [UNESP]Hussni, Carlos Alberto [UNESP]Takahira, Regina Kiomi [UNESP]Nóbrega, Rafael Henrique [UNESP]Martinez, Emanuel Ricardo Monteiro [UNESP]Jackson, Christopher JohnMaia, Gabriela Lemos de AzevedoRozza, Ariane Leite [UNESP]Pellizzon, Cláudia Helena [UNESP]2020-12-12T02:15:45Z2020-12-12T02:15:45Z2020-07-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1-22http://dx.doi.org/10.3390/ijms21144952International Journal of Molecular Sciences, v. 21, n. 14, p. 1-22, 2020.1422-00671661-6596http://hdl.handle.net/11449/20077510.3390/ijms211449522-s2.0-8508815549700193937798010690000-0002-4494-4180Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Sciencesinfo:eu-repo/semantics/openAccess2021-10-27T11:06:35Zoai:repositorio.unesp.br:11449/200775Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-27T11:06:35Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers |
title |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers |
spellingShingle |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers Beserra, Fernando Pereira [UNESP] Cutaneous wound healing Lupeol Natural product Skin regeneration Triterpene |
title_short |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers |
title_full |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers |
title_fullStr |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers |
title_full_unstemmed |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers |
title_sort |
From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers |
author |
Beserra, Fernando Pereira [UNESP] |
author_facet |
Beserra, Fernando Pereira [UNESP] Gushiken, Lucas Fernando Sérgio [UNESP] Vieira, Ana Júlia [UNESP] Bérgamo, Danilo Augusto [UNESP] Bérgamo, Patrícia Luísa [UNESP] de Souza, Mariana Oliveira [UNESP] Hussni, Carlos Alberto [UNESP] Takahira, Regina Kiomi [UNESP] Nóbrega, Rafael Henrique [UNESP] Martinez, Emanuel Ricardo Monteiro [UNESP] Jackson, Christopher John Maia, Gabriela Lemos de Azevedo Rozza, Ariane Leite [UNESP] Pellizzon, Cláudia Helena [UNESP] |
author_role |
author |
author2 |
Gushiken, Lucas Fernando Sérgio [UNESP] Vieira, Ana Júlia [UNESP] Bérgamo, Danilo Augusto [UNESP] Bérgamo, Patrícia Luísa [UNESP] de Souza, Mariana Oliveira [UNESP] Hussni, Carlos Alberto [UNESP] Takahira, Regina Kiomi [UNESP] Nóbrega, Rafael Henrique [UNESP] Martinez, Emanuel Ricardo Monteiro [UNESP] Jackson, Christopher John Maia, Gabriela Lemos de Azevedo Rozza, Ariane Leite [UNESP] Pellizzon, Cláudia Helena [UNESP] |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) The University of Sydney at Royal North Shore Hospital Federal University of São Francisco Valley (UNIVASF) |
dc.contributor.author.fl_str_mv |
Beserra, Fernando Pereira [UNESP] Gushiken, Lucas Fernando Sérgio [UNESP] Vieira, Ana Júlia [UNESP] Bérgamo, Danilo Augusto [UNESP] Bérgamo, Patrícia Luísa [UNESP] de Souza, Mariana Oliveira [UNESP] Hussni, Carlos Alberto [UNESP] Takahira, Regina Kiomi [UNESP] Nóbrega, Rafael Henrique [UNESP] Martinez, Emanuel Ricardo Monteiro [UNESP] Jackson, Christopher John Maia, Gabriela Lemos de Azevedo Rozza, Ariane Leite [UNESP] Pellizzon, Cláudia Helena [UNESP] |
dc.subject.por.fl_str_mv |
Cutaneous wound healing Lupeol Natural product Skin regeneration Triterpene |
topic |
Cutaneous wound healing Lupeol Natural product Skin regeneration Triterpene |
description |
Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:15:45Z 2020-12-12T02:15:45Z 2020-07-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/ijms21144952 International Journal of Molecular Sciences, v. 21, n. 14, p. 1-22, 2020. 1422-0067 1661-6596 http://hdl.handle.net/11449/200775 10.3390/ijms21144952 2-s2.0-85088155497 0019393779801069 0000-0002-4494-4180 |
url |
http://dx.doi.org/10.3390/ijms21144952 http://hdl.handle.net/11449/200775 |
identifier_str_mv |
International Journal of Molecular Sciences, v. 21, n. 14, p. 1-22, 2020. 1422-0067 1661-6596 10.3390/ijms21144952 2-s2.0-85088155497 0019393779801069 0000-0002-4494-4180 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Molecular Sciences |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1-22 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799964672781189120 |