| Texto completo | |
| Autor(es): |
Oda, Fernando Bombarda
;
Carvalho, Flavio Alexandre
;
Yamamoto, Priscila Akemi
;
de Oliveira, Jonata Augusto
;
Peccinini, Rosangela Goncalves
;
Zocolo, Guilherme Juliao
;
Ribeiro, Paulo Riceli Vasconcelos
;
de Moraes, Natalia Valadares
;
dos Santos, Andre Gonzaga
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Planta Medica; v. 89, n. 11, p. 9-pg., 2023-05-26. |
| Resumo | |
Oral 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 KM values of 61.4 and 66.4 mu M and Vmax values 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. (AU) | |
| Processo FAPESP: | 14/50265-3 - Metabolismo e distribuição de xenobióticos naturais e sintéticos: da compreensão dos processos reacionais à geração de imagens teciduais |
| Beneficiário: | Norberto Peporine Lopes |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa BIOTA - Temático |