Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.jep.2019.02.017 http://hdl.handle.net/11449/187356 |
Resumo: | Ethnopharmacological relevance: Copaiba oleoresin has been used in folk medicine in the treatment of bronchitis, syphilis, skin diseases and ulcers due to its anti-inflammatory and antiseptic activities, but there is no information about major compounds oral absorption to support the traditional use. Aim of study: Considering the potential of copalic (CA) and kaurenoic acid (KA) – major biological activity (in vitro) diterpenes found in the oleoresin, this study aimed to evaluate the intestinal permeability of CA and KA using Caco-2 cells model as predictive test for oral drug absorption. Materials and methods: Chemical stability at pH 1.2 and 7.4 and plasma stability were evaluated to mimic physiological conditions of the gastrointestinal tract. The intestinal permeability of CA and KA was evaluated in Caco-2 cells in the presence and absence of the P-glycoprotein inhibitor verapamil. Results: CA and KA were rapidly degraded at pH 1.2 (0.2 M Clark-Lubs buffer). At pH 7.4 (0.1 M phosphate buffer), CA was stable for up to 24 h and KA for up to 6 h. In human plasma, CA and KA can be considered stable for 24 h and 12 h at 37 °C, respectively. Caco-2 cells were considered viable when incubated with CA or KA in the range of 3.9–250 μM for 24 h. CA and KA exhibited moderate apparent permeability (P app ) of 4.67 (±0.08) × 10 −6 cm/s and 4.66 (±0.04) × 10 −6 cm/s, respectively. Simultaneous incubation with verapamil showed that P-glycoprotein does not play a relevant role on CA and KA oral absorption, with P app of 4.48 (±0.26) × 10 −6 cm/s and 5.37 (±0.72) × 10 −6 cm/s observed for CA and KA, respectively. Conclusion: The oral absorption of both CA and KA is driven by mainly passive permeability, is not limited by p-glycoprotein, but enteric-coated dosage forms should be used to avoid chemical instability in the gastric pH. |
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Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cellsCaco-2Copalic acidIntestinal absorptionKaurenoic acidViabilityEthnopharmacological relevance: Copaiba oleoresin has been used in folk medicine in the treatment of bronchitis, syphilis, skin diseases and ulcers due to its anti-inflammatory and antiseptic activities, but there is no information about major compounds oral absorption to support the traditional use. Aim of study: Considering the potential of copalic (CA) and kaurenoic acid (KA) – major biological activity (in vitro) diterpenes found in the oleoresin, this study aimed to evaluate the intestinal permeability of CA and KA using Caco-2 cells model as predictive test for oral drug absorption. Materials and methods: Chemical stability at pH 1.2 and 7.4 and plasma stability were evaluated to mimic physiological conditions of the gastrointestinal tract. The intestinal permeability of CA and KA was evaluated in Caco-2 cells in the presence and absence of the P-glycoprotein inhibitor verapamil. Results: CA and KA were rapidly degraded at pH 1.2 (0.2 M Clark-Lubs buffer). At pH 7.4 (0.1 M phosphate buffer), CA was stable for up to 24 h and KA for up to 6 h. In human plasma, CA and KA can be considered stable for 24 h and 12 h at 37 °C, respectively. Caco-2 cells were considered viable when incubated with CA or KA in the range of 3.9–250 μM for 24 h. CA and KA exhibited moderate apparent permeability (P app ) of 4.67 (±0.08) × 10 −6 cm/s and 4.66 (±0.04) × 10 −6 cm/s, respectively. Simultaneous incubation with verapamil showed that P-glycoprotein does not play a relevant role on CA and KA oral absorption, with P app of 4.48 (±0.26) × 10 −6 cm/s and 5.37 (±0.72) × 10 −6 cm/s observed for CA and KA, respectively. Conclusion: The oral absorption of both CA and KA is driven by mainly passive permeability, is not limited by p-glycoprotein, but enteric-coated dosage forms should be used to avoid chemical instability in the gastric pH.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)São Paulo State University (UNESP) School of Pharmaceutical SciencesFederal University of Mato GrossoUniversity of Sao Paulo (USP) NPPNS School of Pharmaceutical Sciences of Ribeirao PretoSão Paulo State University (UNESP) School of Pharmaceutical SciencesFAPESP: 14/50265-3Universidade Estadual Paulista (Unesp)Federal University of Mato GrossoUniversidade de São Paulo (USP)Mauro, M. [UNESP]De Grandis, R. A. [UNESP]Campos, M. L.Bauermeister, A.Peccinini, R. G. [UNESP]Pavan, F. R. [UNESP]Lopes, N. P.De Moraes, N. V. [UNESP]2019-10-06T15:33:36Z2019-10-06T15:33:36Z2019-05-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article183-189http://dx.doi.org/10.1016/j.jep.2019.02.017Journal of Ethnopharmacology, v. 235, p. 183-189.1872-75730378-8741http://hdl.handle.net/11449/18735610.1016/j.jep.2019.02.0172-s2.0-85061571370Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Ethnopharmacologyinfo:eu-repo/semantics/openAccess2021-10-22T18:33:43Zoai:repositorio.unesp.br:11449/187356Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-22T18:33:43Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells |
title |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells |
spellingShingle |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells Mauro, M. [UNESP] Caco-2 Copalic acid Intestinal absorption Kaurenoic acid Viability |
title_short |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells |
title_full |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells |
title_fullStr |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells |
title_full_unstemmed |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells |
title_sort |
Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells |
author |
Mauro, M. [UNESP] |
author_facet |
Mauro, M. [UNESP] De Grandis, R. A. [UNESP] Campos, M. L. Bauermeister, A. Peccinini, R. G. [UNESP] Pavan, F. R. [UNESP] Lopes, N. P. De Moraes, N. V. [UNESP] |
author_role |
author |
author2 |
De Grandis, R. A. [UNESP] Campos, M. L. Bauermeister, A. Peccinini, R. G. [UNESP] Pavan, F. R. [UNESP] Lopes, N. P. De Moraes, N. V. [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Federal University of Mato Grosso Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Mauro, M. [UNESP] De Grandis, R. A. [UNESP] Campos, M. L. Bauermeister, A. Peccinini, R. G. [UNESP] Pavan, F. R. [UNESP] Lopes, N. P. De Moraes, N. V. [UNESP] |
dc.subject.por.fl_str_mv |
Caco-2 Copalic acid Intestinal absorption Kaurenoic acid Viability |
topic |
Caco-2 Copalic acid Intestinal absorption Kaurenoic acid Viability |
description |
Ethnopharmacological relevance: Copaiba oleoresin has been used in folk medicine in the treatment of bronchitis, syphilis, skin diseases and ulcers due to its anti-inflammatory and antiseptic activities, but there is no information about major compounds oral absorption to support the traditional use. Aim of study: Considering the potential of copalic (CA) and kaurenoic acid (KA) – major biological activity (in vitro) diterpenes found in the oleoresin, this study aimed to evaluate the intestinal permeability of CA and KA using Caco-2 cells model as predictive test for oral drug absorption. Materials and methods: Chemical stability at pH 1.2 and 7.4 and plasma stability were evaluated to mimic physiological conditions of the gastrointestinal tract. The intestinal permeability of CA and KA was evaluated in Caco-2 cells in the presence and absence of the P-glycoprotein inhibitor verapamil. Results: CA and KA were rapidly degraded at pH 1.2 (0.2 M Clark-Lubs buffer). At pH 7.4 (0.1 M phosphate buffer), CA was stable for up to 24 h and KA for up to 6 h. In human plasma, CA and KA can be considered stable for 24 h and 12 h at 37 °C, respectively. Caco-2 cells were considered viable when incubated with CA or KA in the range of 3.9–250 μM for 24 h. CA and KA exhibited moderate apparent permeability (P app ) of 4.67 (±0.08) × 10 −6 cm/s and 4.66 (±0.04) × 10 −6 cm/s, respectively. Simultaneous incubation with verapamil showed that P-glycoprotein does not play a relevant role on CA and KA oral absorption, with P app of 4.48 (±0.26) × 10 −6 cm/s and 5.37 (±0.72) × 10 −6 cm/s observed for CA and KA, respectively. Conclusion: The oral absorption of both CA and KA is driven by mainly passive permeability, is not limited by p-glycoprotein, but enteric-coated dosage forms should be used to avoid chemical instability in the gastric pH. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T15:33:36Z 2019-10-06T15:33:36Z 2019-05-10 |
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/10.1016/j.jep.2019.02.017 Journal of Ethnopharmacology, v. 235, p. 183-189. 1872-7573 0378-8741 http://hdl.handle.net/11449/187356 10.1016/j.jep.2019.02.017 2-s2.0-85061571370 |
url |
http://dx.doi.org/10.1016/j.jep.2019.02.017 http://hdl.handle.net/11449/187356 |
identifier_str_mv |
Journal of Ethnopharmacology, v. 235, p. 183-189. 1872-7573 0378-8741 10.1016/j.jep.2019.02.017 2-s2.0-85061571370 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Ethnopharmacology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
183-189 |
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_ |
1803046467045163008 |