Herbal extracts used in folk medicine are complex mixtures of natural products (NPs). Their efficacy in vivo after ingestion depends on their uptake (and sometimes their metabolites) in the gastrointestinal tract. The correlation of bioactivities measured in vitro with efficacy in vivo is a challenge since bioavailability and biotransformation can have an impact.[1] We have validated an ex vivo model using viable porcine small intestine to elucidate the effects of absorption and intestinal metabolism on drug uptake (manuscript in preparation). Porcine intestine closely resembles its human counterpart in terms of physiology and function; active and passive transport mechanisms are observed and similar metabolizing enzymes are present.[2] Representative NPs and their parent herbal extracts were selected and the permeation across porcine jejunum, harvested immediately after slaughter, was studied using an Ussing chamber system.[2] Aliquots from the donor and acceptor compartments were analyzed by non-targeted UHPLC-HRMS to enable metabolite profiling and the permeation of the NPs was quantified by targeted UHPLC-MS-MRM. Results with Pueraria lobata indicated that, in contrast to observations with PAMPA [3] the C-glycoside puerarin and the aglycone daidzein were able to permeate; the different behavior was most likely due to differences in molecule partitioning and possibly to active transport. However, the corresponding O-glycoside, daidzin, showed no permeation but was extensively metabolized. This was observed for the pure constituent and the decoction – demonstrating the importance of pre-systemic metabolism. Tests with other NPs confirmed that this ex vivo model was well-suited to investigating the bioavailability of isolated NPs and components from complex extracts. Although not a high throughput system, it enables a much deeper understanding of the roles and impact of permeability and metabolism on bioavailability.
[1] Butterweck V, Nahrstedt A. Planta Medica: 2012; 78: 747 – 754.
[2] Sjögren et al. Eur J Pharm Sci: 2014; 57: 99 – 151.
[3] Petit C et al. Planta Medica:2016; 82: 424 – 431.
