In-vitro mutagenic potential and effect on permeability of co-administered drugs across Caco-2 cell monolayers of Rubus idaeus and its fortified fractions.

This study investigated the mutagenic, anti-mutagenic and cytotoxic effects of acetone extract of raspberry, Rubus idaeus L. (v. Ottawa) Rosaceae, and the isolated and characterized ellagitannin and anthocyanin fractions thereof, suitable for food applications. The studied raspberry extract and fractions did not show any mutagenic effects determined in the miniaturized Ames test and were not cytotoxic to Caco-2 cells at the used concentrations. However, the anti-mutagenic properties were changed (i.e. decreased mutagenicity of 2-nitrofluorene in strain TA98, and slightly increased mutagenicity of 2-aminoanthracene in strain TA100) with metabolic activation. Further, their influence on the permeability of co-administered common drugs (ketoprofen, paracetamol, metoprolol and verapamil) across Caco-2 monolayers was evaluated. The apical-to-basolateral permeability of highly permeable verapamil was mostly affected (decreased) during co-administration of the raspberry extract or the ellagitannin fraction. Ketoprofen permeability was decreased by the ellagitannin fraction. Consumption of food rich in phytochemicals, as demonstrated here with chemically characterized raspberry extract and fractions, with well-absorbing drugs would seem to affect the permeability of some of these drugs depending on the components. Thus their effects on the absorption of drugs in-vivo cannot be excluded.

Preclinical evaluation of rapeseed, raspberry, and pine bark phenolics for health related effects.

Rapeseed, raspberry, and pine bark are promising bioactive sources of plant phenolics selected from among ca. 100 previously screened plant materials for in vitro preclinical evaluation of health related effects. Phenolic extracts and isolated fractions of the selected materials were investigated for antioxidant, antimicrobial, antiinflammatory, and antimutagenic properties as well as for cell permeability. It was shown that rapeseed and pine bark phenolics and raspberry anthocyanins were good or excellent antioxidants toward oxidation of phosphatidylcholine membrane (liposomes), rapeseed oil (crude) phenolics were effective radical scavengers (DPPH test), and both raspberry and pine bark phenolics inhibited LDL oxidation. Rapeseed oil phenolics, principally vinylsyringol, raspberry anthocyanins, and pinoresinol and matairesinol, the principal components of pine bark phenolic isolate, were effective against formation of the proinflammatory mediator, prostaglandin E(2). Raspberry ellagitannins inhibited the growth of Proteus mirabilis and Klebsiella oxytoca. Pine bark and rapeseed had minor effects on the permeability of model drugs in Caco-2 experiments. None of the tested extracts were mutagenic nor toxic to Caco-2 cells or macrophages. Thus, phenolic isolates from rapeseed, raspberry, and pine bark and are safe and bioactive for possible food applications including functional foods intended for health benefit.