Abstract
Hymenocardine is a cyclopeptide alkaloid present in the root bark of Hymenocardia acida. In traditional African medicine, the leaves and roots of this plant are used to
treat malaria, and moderate in vitro antiplasmodial activity has been reported for hymenocardine. However, in view of
its peptide-like nature, potential metabolisation after oral ingestion has to be taken
into account when considering in vivo experiments. In this study, the stability and small intestinal absorption of hymenocardine
was assessed using an in vitro gastrointestinal dialysis model. In addition, potential liver metabolisation was
investigated in vitro by incubation with a human S9 fraction. Moreover, hymenocardine was administered
to rats per os, and blood and urine samples were collected until 48 and 24 h after oral administration,
respectively. All samples resulting from these three experiments were analyzed by
LC-MS. Analysis of the dialysate and retentate, obtained from the gastrointestinal
dialysis model, indicated that hymenocardine is absorbed unchanged from the gastrointestinal
tract, at least in part. After S9 metabolisation, several metabolites of hymenocardine
could be identified, the major ones being formed by the reduction and/or the loss
of an N-methyl group. The in vivo study confirmed that hymenocardine is absorbed from the gastrointestinal tract unchanged,
since it could be identified in both rat plasma and urine, together with hymenocardinol,
its reduction product.
Key words
Hymenocardia acida
- Phyllantaceae - hymenocardine - absorption - metabolisation
