Evaluation of passive permeability through GIT of a set of natural compounds and plant extracts with the Hexadecane Membrane Parallel Artificial Membrane Permeability Assay

Abstract

Many high-throughput screening (HTS) assays have been developed for the early stage of drug discovery to predict ADMET (absorption, distribution, metabolism, elimination, toxicity) properties. The Parallel Artificial Membrane Permeability Assay (PAMPA) is a HTS tool to predict passive absorption of drugs through biological membranes [1]; such as the hexadecane artificial membrane (HDM) which predicts passive absorption for the gastrointestinal track (GIT) [2]. While many studies concern the prediction of pharmacokinetic of commercial drugs, studies focusing on natural products are sparse. Recently, the applicability of PAMPA to natural products and plant extracts was demonstrated for the Blood Brain Barrier [3]. The present study focuses on the prediction of passive permeability through GIT of natural compounds with the original HDM-PAMPA. Firstly, major classes of plant secondary metabolites such as alkaloids, flavonoid aglycones and glycosides, coumarins and carboxylic acids were tested with HDM-PAMPA at different iso-pH [2]. The compounds were discriminated from high to low permeant depending on their chemical families. Hydrophilic flavonoid glycosides were not permeant, unlike some of their corresponding aglycones. Alkaloids, carboxylic acids and coumarins were permeant depending on iso-pH conditions. Secondly, a crude methanolic fruit extract of Angelica archangelica containing three furanocoumarins (imperatorin, bergapten and xanthotoxin) and an acetonic leaves extract of Ginkgo biloba containing flavonoid glycosides were studied with HDM-PAMPA. The presence of the plant extract matrix in the assay showed no influence on the passive permeability values of these selected compounds. The results were in agreement with the above study concerning the various phytochemical families. This work has demonstrated the applicability of the HDM-PAMPA assay to predict passive absorption through the GIT of natural compounds and plant extracts.