Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells

Autor(es)

Mauro, M. ^[1] ; De Grandis, R. A. ^[1] ; Campos, M. L. ^[2] ; Bauermeister, A. ^[3] ; Peccinini, R. G. ^[1] ; Pavan, F. R. ^[1] ; Lopes, N. P. ^[3] ; De Moraes, V, N.

Afiliação do(s) autor(es)

^[1] V, Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Rodovia Araraquara Jau, Km 01, BR-14801902 Araraquara, SP - Brazil

^[2] Univ Fed Mato Grosso, Sinop, MT - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, NPPNS, BR-14040903 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Ethnopharmacology; v. 235, p. 183-189, MAY 10 2019.
• Citações Web of Science: 0

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 hat 37 `C, respectively. Caco-2 cells were considered viable when incubated with CA or KA in the range of 3.9-250 mu M for 24 h. CA and KA exhibited moderate apparent permeability (P-app) of 4.67 (+/- 0.08) x 10(-6) cm/s and 4.66 ( +/- 0.04) x 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) x 10(-6) cm/s and 5.37 ( +/- 0.72) x 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. (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
• Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático