Matrix effects of the hydroethanolic extract and the butanol fraction of calyces from Physalis peruviana L. on the biopharmaceutics classification of rutin.

OBJECTIVES: The Biopharmaceutics Classification System (BCS) categorizes active pharmaceutical ingredients according to their solubility and permeability properties, which are susceptible to matrix or formulation effects. The aim of this research was to evaluate the matrix effects of a hydroethanolic extract of calyces from Physalis peruviana L. (HEE) and its butanol fraction (BF), on the biopharmaceutics classification of their major compound, quercetin-3-O-rutinoside (rutin, RU). METHODS: Rutin was quantified by HPLC-UV, and Caco-2 cell monolayer transport studies were performed to obtain the apparent permeability values (Papp ). Aqueous solubility was determined at pH 6.8 and 7.4. KEY FINDINGS: The Papp values followed this order: BF > HEE > RU (1.77 ± 0.02 > 1.53 ± 0.07 > 0.90 ± 0.03 × 10-5  cm/s). The lowest solubility values followed this order: HEE > RU > BF (2.988 ± 0.07 > 0.205 ± 0.002 > 0.189 ± 0.005 mg/ml). CONCLUSIONS: According to these results, rutin could be classified as BCS classes III (high solubility/low permeability) and IV (low solubility/low permeability), depending on the plant matrix. Further work needs to be done in order to establish how apply the BCS for research and development of new botanical drugs or for bioequivalence purposes.

Development of Caco-2 cells-based gene reporter assays and evaluation of herb-drug interactions involving CYP3A4 and CYP2D6 gene expression.

The indiscriminate use of medicinal plants and herbal medicinal products concomitantly with conventional drugs may result in herb-drug interactions that may lead to fluctuations in drug bioavailability, therapeutic failure, and/or toxic effects. CYP450 enzymes play an important role in drug biotransformation and herb-drug interactions. Thus, the aim of this study was to develop and apply Caco-2 cells-based gene reporter assays to study in vitro the potential occurrence of CYP3A4 and CYP2D6 gene expression modulation by standardized extracts of selected medicinal plants. Reporter cell lines developed showed a significant increase in CYP3A4 and CYP2D6 reporter fluorescent emission, 4 and 16-fold respectively, when compared to the controls. The standardized extracts of Cecropia glaziovii, Bauhinia forficata and Echinacea sp. significantly increased CYP3A4 reporter fluorescence, and those of Ilex paraguariensis, Bauhinia forficata and Echinacea sp. significantly decreased CYP2D6 reporter fluorescence in Caco-2 cells-based gene reporter assays. The data obtained suggest that CYP3A4 and CYP2D6 gene expression seem to be modulated by the extracts tested. In addition, the reporter cell lines developed are functional assays that could be used to study drug-drug and herb-drug interactions during the research and development of new drugs.