Polygodial, a sesquiterpene isolated from Drimys brasiliensis (Winteraceae), triggers glucocorticoid-like effects on pancreatic beta-cells

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dc.contributor.author Barrosa, Kaidu Hanashiro [UNIFESP]
dc.contributor.author Mecchi, Murilo C. [UNIFESP]
dc.contributor.author Rando, Daniela Goncales [UNIFESP]
dc.contributor.author Ferreira, Ari Jose S.
dc.contributor.author Sartorelli, Patricia [UNIFESP]
dc.contributor.author Valle, Maira M. R.
dc.contributor.author Bordin, Silvana
dc.contributor.author Caperuto, Luciana Chagas [UNIFESP]
dc.contributor.author Lago, Joao Henrique Ghilardi [UNIFESP]
dc.contributor.author Lellis-Santos, Camilo [UNIFESP]
dc.date.accessioned 2020-07-31T12:47:32Z
dc.date.available 2020-07-31T12:47:32Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.1016/j.cbi.2016.09.013
dc.identifier.citation Chemico-Biological Interactions. Clare, v. 258, p. 245-256, 2016.
dc.identifier.issn 0009-2797
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/56885
dc.description.abstract Despite its common use, the synthetic glucocorticoid dexamethasone can cause several adverse effects, such as diabetes and insulin-related metabolic impairment. Thus, research on molecules that could provide the same anti-inflammatory response with milder side effects is constant. In this work the antiinflammatory activity of the natural sesquiterpene polygodial, extracted from the endemic Brazilian plant Drimys brasiliensis Miers (Winteraceae), was investigated. Employing a pancreatic beta-cell model (INS 1E), the effect of polygodial on signaling pathways is similar to that caused by dexamethasone - both increased MKP1 and decreased ERK1/2 expression in a dose-response and time-dependent manner. Relating to such finding, nuclear translocation of the glucocorticoid receptor was also discovered to be induced by the sesquiterpene. Molecular modeling results indicated that polygodial was capable of docking to the glucocorticoid receptor, but presented preference for the Arg611 binding site rather than Thr739 when set to bind freely inside the pocket. At last, fragmentation of DNA was verified as consequence of sesquiterpene-induced cell death. Altogether, our results suggest that, like dexamethasone, polygodial interacts the glucocorticoid receptor ligand binding domain but create fewer ligand-protein interactions at the site, yielding a weaker effector response. Such property provides an advantage when regarding the adverse effects resulting from stronger affinity ligands of the glucocorticoid receptor, such as in the case of the current standard dexamethasone-based treatment. This aspect, also, turns polygodial an interesting hit compound to the development of new drugs based on its backbone structure providing less harmful anti-inflammatory treatments. (C) 2016 Elsevier Ireland Ltd. All rights reserved. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 245-256
dc.language.iso eng
dc.publisher Elsevier Ireland Ltd
dc.relation.ispartof Chemico-Biological Interactions
dc.rights Acesso restrito
dc.subject Poligodial en
dc.subject Dexamethasone en
dc.subject beta-Cells en
dc.subject Glucocorticoid receptor en
dc.subject Nuclear translocation en
dc.subject Molecular docking en
dc.title Polygodial, a sesquiterpene isolated from Drimys brasiliensis (Winteraceae), triggers glucocorticoid-like effects on pancreatic beta-cells en
dc.type Artigo
dc.description.affiliation Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Sao Paulo, Brazil
dc.description.affiliation Ctr Univ Fundacao, Inst Ensino Osasco, Ctr Estudos Quim, BR-06020190 Sao Paulo, Brazil
dc.description.affiliation Univ Sao Paulo, Inst Biomed Sci, BR-05508900 Sao Paulo, Brazil
dc.description.affiliation Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210180 Sao Paulo, Brazil
dc.description.affiliationUnifesp Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270, São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2015/11936-2
dc.description.sponsorshipID FAPESP: 2010/10778-0
dc.identifier.doi 10.1016/j.cbi.2016.09.013
dc.description.source Web of Science
dc.identifier.wos WOS:000385368700026
dc.coverage Clare
dc.citation.volume 258


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