In Vitro and In Vivo Study of the Gastrointestinal Absorption and Metabolisation of Hymenocardine, a Cyclopeptide Alkaloid.
Hymenocardine is a cyclopeptide alkaloid present in the root bark ofHymenocardia acida. In traditional African medicine, the leaves and roots of this plant are used to treat malaria, and moderatein vitroantiplasmodial 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 consideringin vivoexperiments. In this study, the stability and small intestinal absorption of hymenocardine was assessed using anin vitrogastrointestinal dialysis model. In addition, potential liver metabolisation was investigatedin vitroby incubation with a human S9 fraction. Moreover, hymenocardine was administered to ratsper 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 anN-methyl group. Thein vivostudy 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.
Natural Products & Food Research and Analysis (NatuRA), University of Antwerp, Antwerp, Belgium.
Emmy
E
Tuenter
Natural Products & Food Research and Analysis (NatuRA), University of Antwerp, Antwerp, Belgium.|Flemish Institute for Technological Research (VITO), Business Unit Separation and Conversion Technology (SCT), Mol, Belgium.
Sebastiaan
S
Bijttebier
Natural Products & Food Research and Analysis (NatuRA), University of Antwerp, Antwerp, Belgium.
Kenn
K
Foubert
Natural Products & Food Research and Analysis (NatuRA), University of Antwerp, Antwerp, Belgium.
Annelies
A
Breynaert
Natural Products & Food Research and Analysis (NatuRA), University of Antwerp, Antwerp, Belgium.
Sandra
S
Apers
Natural Products & Food Research and Analysis (NatuRA), University of Antwerp, Antwerp, Belgium.
Nina
N
Hermans
Natural Products & Food Research and Analysis (NatuRA), University of Antwerp, Antwerp, Belgium.
Luc
L
Pieters
D000470:Alkaloids / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D000818:Animals; D005591:Chemical Fractionation; D019669:Embryophyta / Q000737:chemistry*; D065569:Gastrointestinal Absorption; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D016488:Medicine, African Traditional; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D010936:Plant Extracts / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
D000470:Alkaloids; D010456:Peptides, Cyclic; D010936:Plant Extracts; C000624618:hymenocardine