Planta Med 2015; 81 - SL1A_03
DOI: 10.1055/s-0035-1565287

High-throughput prediction of passive intestinal absorption of natural products and plant extracts with the PAMPA assay

C Petit 1, A Bujard 1, K Skalicka-Woźniak 2, S Cretton 1, J Houriet 1, P Christen 1, PA Carrupt 1, JL Wolfender 1
  • 1School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, Geneva, Switzerland
  • 2Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, 1 Chodzki Street, Lublin, Poland

At early drug discovery stage, the high-throughput Parallel Artificial Membrane Permeability Assay (PAMPA) is one of the most frequently used in vitro model to predict transcellular passive absorption. While thousands of new chemical entities have been screened with PAMPA, in general permeation properties of natural products (NPs) have been scarcely evaluated. In this study, the Hexadecane Membrane (HDM) PAMPA was used to predict the passive intestinal absorption of a set of NPs. Alkaloids, coumarins and methoxylated flavonoid aglycones showed favourable passive intestinal absorption potential while flavonoid gylcosides and acidic NPs were found to have low passive intestinal absorption. To maintain a relatively high-throughput assay, a generic UHPLC-UV detection method was used and allowed easy calculation of the effective passive permeability value Pe (cm/s) of each NP without the need for specific compound dependent detection.

Since NPs are usually ingested in medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of HDM-PAMPA to screen crude extracts was further investigated based on three extracts containing chemically diverse active NPs. The first extract was composed of lipophilic furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica) and the third extract contained polar flavonoid glycosides (Pueraria lobata). The effective passive permeability values Pe of major NPs in the extracts were rapidly estimated based on UHPLC-UV profiles and were found not to be affected by the presence of other constituents in the extracts.

HDM-PAMPA/UHPLC-UV is a cost-effective and high-throughput method to evaluate transcellular passive intestinal absorption of plant active principles. Early evaluation of absorption is important to predict if NPs showing interesting activities in vitro may have a chance to reach their target in vivo.