Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

Abstract

At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high-throughput, cost-effective, and early evaluation of passive intestinal absorption of active principles in medicinal plants. In phytochemical studies, obtaining effective passive permeability values of pharmacologically active natural products is important to predict if natural products showing interesting activities in vitro may have a chance to reach their target in vivo.

Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

“…However, its applicability is extremely restricted due to its complexity, high cost, and ethical considerations. Several in vitro and in situ methods were developed for the measurement of permeability, including the parallel artificial membrane permeability assay, [24][25][26][27] everted gut sacs, [28][29][30] Ussing side-by-side diffusion chambers, 12,[31][32][33][34] Caco-2 monolayers, [35][36][37] and intestinal perfusion models for example, the rat single-pass intestinal perfusion (SPIP), [38][39][40][41] and the Doluisio technique. 37,[42][43][44] These methods are now well established and frequently used; yet, to assess segmental-dependent intestinal absorption throughout the GIT, rat intestinal perfusion still remain the most significant experimental method.…”

Development and Evaluation of Lipid Nanoparticles Containing Natural Botanical Oil for Sun Protection: Characterization and in vitro and in vivo Human Skin Permeation and Toxicity

“…We followed this approach by developing SLNs loaded with vegetable oils from Brazilian flora, which is rich in antioxidant substances. We used a powerful multiphoton imaging technique (MPT-FLIM) to verify interaction between formulations and skin in human volunteers, as well as ex vivo (Franz cell) tests of skin permeation [18,19,24,25,26]. …”

StandardizedPassiflora incarnataL. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats

“…It has been reported that deglycosylation of such compounds by β‐glucosidase in the small intestine and by the colonic microflora is often required before absorption can occur. The flavonoids aglycones, either occurring as such in plants or resulting from hydrolysis, displayed various permeability behaviors (Petit et al, ).…”