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Metadados | Descrição | Idioma |
---|---|---|
Autor(es): dc.contributor | Universidade Estadual Paulista (Unesp) | - |
Autor(es): dc.creator | Tanimoto, Alexandre [UNESP] | - |
Autor(es): dc.creator | Witaicenis, Aline [UNESP] | - |
Autor(es): dc.creator | Caruso, Ícaro P. [UNESP] | - |
Autor(es): dc.creator | Piva, Hémily M.R. [UNESP] | - |
Autor(es): dc.creator | Araujo, Gabriela C. [UNESP] | - |
Autor(es): dc.creator | Moraes, Fábio R. [UNESP] | - |
Autor(es): dc.creator | Fossey, Marcelo C. [UNESP] | - |
Autor(es): dc.creator | Cornélio, Marinonio L. [UNESP] | - |
Autor(es): dc.creator | Souza, Fátima P. [UNESP] | - |
Autor(es): dc.creator | Di Stasi, Luiz C. [UNESP] | - |
Data de aceite: dc.date.accessioned | 2022-02-22T00:27:49Z | - |
Data de disponibilização: dc.date.available | 2022-02-22T00:27:49Z | - |
Data de envio: dc.date.issued | 2020-12-11 | - |
Data de envio: dc.date.issued | 2020-12-11 | - |
Data de envio: dc.date.issued | 2020-01-04 | - |
Fonte completa do material: dc.identifier | http://dx.doi.org/10.1016/j.cbi.2019.108876 | - |
Fonte completa do material: dc.identifier | http://hdl.handle.net/11449/199607 | - |
Fonte: dc.identifier.uri | http://educapes.capes.gov.br/handle/11449/199607 | - |
Descrição: dc.description | 4-methylesculetin (4 ME) is a natural antioxidant coumarin with protective effects on the intestinal inflammation, in which oxidative stress plays a key role in its aetiology and pathophysiology. Based on this, we examined the antioxidant molecular mechanisms involved in the intestinal anti-inflammatory activity of the 4 ME. For this purpose, we investigated the effects of the 4 ME on the modulation of gene expression and antioxidant-related enzyme activities in TNBS model of intestinal inflammation as well as the molecular interaction between 4 ME and glutathione reductase. Our results showed that 4 ME modulated glutathione-related enzymes, mainly increasing glutathione reductase activity. These effects were related to upregulation of glutathione reductase and Nrf2 gene expression. Fluorescence and nuclear magnetic resonance data showed that interaction between 4 ME and glutathione reductase is collisional, hydrophobic and spontaneous, in which C4 methyl group is the second epitope most buried into glutathione reductase. Molecular modelling calculation showed Lys70-B, Arg81-A, Glu381-B, Asp443-A, Ser444-A, Glu447-B and Ser475-A participated in electrostatic interaction, Lys70-B, Glu381-B and Arg81-A acted in the hydrophobic interactions and Trp73, Phe377 and Ala446 are responsible for the hydrogen bonds. Based on this, our results showed 4 ME acted by different mechanisms to control oxidative stress induced by intestinal damage, controlling the imbalance between myeloperoxidase activity and glutathione production, upregulating the glutathione S-transferase and glutathione reductase activities, preventing the Nrf2 and glutathione gene expression downregulation with consequent glutathione maintenance. Finally, 4 ME interacted at molecular level with glutathione reductase, stabilizing its enzymatic activity and reducing oxidative stress to take place in intestinal inflammatory process. | - |
Descrição: dc.description | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) | - |
Descrição: dc.description | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | - |
Descrição: dc.description | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) | - |
Descrição: dc.description | Laboratory of Phytomedicines Pharmacology and Biotechnology (PhytoPharmaTech) Department of Pharmacology Institute of Biosciences UNESP São Paulo State University, Botucatu | - |
Descrição: dc.description | Multi-user Biomolecular Innovation Center (CMIB) Department de Physics Institute of Biosciences Letters e Exact Sciences (IBILCE) UNESP São Paulo State University, Rua Cristovão Colombo, 2265, Jardim Nazareth, São José do Rio Preto | - |
Descrição: dc.description | Laboratory of Phytomedicines Pharmacology and Biotechnology (PhytoPharmaTech) Department of Pharmacology Institute of Biosciences UNESP São Paulo State University, Botucatu | - |
Descrição: dc.description | Multi-user Biomolecular Innovation Center (CMIB) Department de Physics Institute of Biosciences Letters e Exact Sciences (IBILCE) UNESP São Paulo State University, Rua Cristovão Colombo, 2265, Jardim Nazareth, São José do Rio Preto | - |
Descrição: dc.description | FAPESP: 2015/15267-8 | - |
Idioma: dc.language | en | - |
Relação: dc.relation | Chemico-Biological Interactions | - |
???dc.source???: dc.source | Scopus | - |
Palavras-chave: dc.subject | 4-Methylesculetin | - |
Palavras-chave: dc.subject | Glutathione | - |
Palavras-chave: dc.subject | Glutathione reductase | - |
Palavras-chave: dc.subject | Glutathione-related enzymes | - |
Palavras-chave: dc.subject | Inflammatory bowel disease | - |
Palavras-chave: dc.subject | Nrf2 | - |
Título: dc.title | 4-Methylesculetin, a natural coumarin with intestinal anti-inflammatory activity, elicits a glutathione antioxidant response by different mechanisms | - |
Tipo de arquivo: dc.type | livro digital | - |
Aparece nas coleções: | Repositório Institucional - Unesp |
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