Metabolism Characterization and Chemical and Plasma Stability of Casearin B and Caseargrewiin F

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversity of Florida-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorEmpresa Brasileira de Pesquisa Agropecuária (EMBRAPA)-
Autor(es): dc.creatorOda, Fernando Bombarda-
Autor(es): dc.creatorCarvalho, Flávio Alexandre-
Autor(es): dc.creatorYamamoto, Priscila Akemi-
Autor(es): dc.creatorDe Oliveira, Jonata Augusto-
Autor(es): dc.creatorPeccinini, Rosângela Gonçalves-
Autor(es): dc.creatorZocolo, Guilherme Julião-
Autor(es): dc.creatorRibeiro, Paulo Riceli Vasconcelos-
Autor(es): dc.creatorDe Moraes, Natália Valadares-
Autor(es): dc.creatorDos Santos, André Gonzaga-
Data de aceite: dc.date.accessioned2025-08-21T15:55:59Z-
Data de disponibilização: dc.date.available2025-08-21T15:55:59Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-02-11-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1055/a-2078-5920-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/304156-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/304156-
Descrição: dc.descriptionOral preparations of Casearia sylvestris (guacatonga) are used as antacid, analgesic, anti-inflammatory, and antiulcerogenic medicines. The clerodane diterpenes casearin B and caseargrewiin F are major active compounds in vitro and in vivo. The oral bioavailability and metabolism of casearin B and caseargrewiin F were not previously investigated. We aimed to assess the stability of casearin B and caseargrewiin F in physiological conditions and their metabolism in human liver microsomes. The compounds were identified by UHPLC-QTOF-MS/MS and quantified by validated LC-MS methods. The stability of casearin B and caseargrewiin F in physiological conditions was assessed in vitro. Both diterpenes showed a fast degradation (p < 0.05) in simulated gastric fluid. Their metabolism was not mediated by cytochrome P-450 enzymes, but the depletion was inhibited by the esterase inhibitor NaF. Both diterpenes and their dialdehydes showed a octanol/water partition coefficient in the range of 3.6 to 4.0, suggesting high permeability. Metabolism kinetic data were fitted to the Michaelis-Menten profile with K Mvalues of 61.4 and 66.4 μM and V maxvalues of 327 and 648 nmol/min/mg of protein for casearin B and caseargrewiin F, respectively. Metabolism parameters in human liver microsomes were extrapolated to predict human hepatic clearance, and suggest that caseargrewiin F and casearin B have a high hepatic extraction ratio. In conclusion, our data suggest that caseargrewiin F and casearin B present low oral bioavailability due to extensive gastric degradation and high hepatic extraction.-
Descrição: dc.descriptionDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (Unesp), SP-
Descrição: dc.descriptionCenter of Pharmacometrics and Systems Pharmacology Department of Pharmaceutics College of Pharmacy University of Florida-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences of Ribeirão Preto University of São Palo (USP), SP-
Descrição: dc.descriptionEmbrapa Agroindústria Tropical Empresa Brasileira de Pesquisa Agropecuária (Embrapa), CE-
Descrição: dc.descriptionDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (Unesp), SP-
Formato: dc.format1097-1105-
Idioma: dc.languageen-
Relação: dc.relationPlanta Medica-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectCasearia sylvestris-
Palavras-chave: dc.subjectclerodane diterpene-
Palavras-chave: dc.subjecthepatic metabolism-
Palavras-chave: dc.subjectIVIVE-
Palavras-chave: dc.subjectSalicaceae-
Título: dc.titleMetabolism Characterization and Chemical and Plasma Stability of Casearin B and Caseargrewiin F-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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