title: Intestinal Transport Characteristics and Metabolism of C-Glucosyl Dihydrochalcone, Aspalathin.
abstract: Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1-150 µM had an apparent rate of permeability (Papp) typical of poorly absorbed compounds (1.73 × 10-6cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1.84 × 10-6cm/s; efflux ratio: 1.1) were excluded as primary transporters, since the Pappof aspalathin was not affected by the presence of specific inhibitors. The Pappof aspalathin was also not affected by constituents of aspalathin-enriched rooibos extracts, but was affected by high glucose concentration (20.5 mM), which decreased the Pappvalue to 2.9 × 10-7cm/s. Aspalathin metabolites (sulphated, glucuronidated and methylated) were found in mouse urine, but not in blood, following an oral dose of 50 mg/kg body weight of the pure compound. Sulphates were the predominant metabolites. These findings suggest that aspalathin is absorbed and metabolised in mice to mostly sulphate conjugates detected in urine. Mechanistically, we showed that aspalathin is not actively transported by the glucose transporters, but presumably passes the monolayer paracellularly.
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7130, South Africa. sandra.bowles@mrc.ac.za.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bowles
authors.affiliation: Plant Bioactives Group, Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Stellenbosch 7600, South Africa. JoubertL@arc.agric.za.|Department of Food Science, Stellenbosch University, Stellenbosch 7600, South Africa. JoubertL@arc.agric.za.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joubert
authors.affiliation: Plant Bioactives Group, Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Stellenbosch 7600, South Africa. DBeerD@arc.agric.za.|Department of Food Science, Stellenbosch University, Stellenbosch 7600, South Africa. DBeerD@arc.agric.za.
authors.forename: Dalene
authors.initials: D
authors.lastname: de Beer
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7130, South Africa. johan.louw@mrc.ac.za.|Department of Biochemistry and Microbiology, University of Zululand, Kwa-Dlangezwa 3886, South Africa. johan.louw@mrc.ac.za.
authors.forename: Johan
authors.initials: J
authors.lastname: Louw
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa. CA.brunschwig@uct.ac.za.|Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa. CA.brunschwig@uct.ac.za.|Division of Clinical Pharmacology, University of Cape Town, Observatory, Cape Town 7925, South Africa. CA.brunschwig@uct.ac.za.
authors.forename: Christel
authors.initials: C
authors.lastname: Brunschwig
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa. Mathew.Njoroge@uct.ac.za.|Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa. Mathew.Njoroge@uct.ac.za.|Division of Clinical Pharmacology, University of Cape Town, Observatory, Cape Town 7925, South Africa. Mathew.Njoroge@uct.ac.za.
authors.forename: Mathew
authors.initials: M
authors.lastname: Njoroge
authors.affiliation: Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa. nina.lawrence@uct.ac.za.
authors.forename: Nina
authors.initials: N
authors.lastname: Lawrence
authors.affiliation: Division of Clinical Pharmacology, University of Cape Town, Observatory, Cape Town 7925, South Africa. lubbe.wiesner@uct.ac.za.
authors.forename: Lubbe
authors.initials: L
authors.lastname: Wiesner
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa. kelly.chibale@uct.ac.za.|Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa. kelly.chibale@uct.ac.za.|Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South Africa. kelly.chibale@uct.ac.za.|South African Medical Research Council Drug, Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa. kelly.chibale@uct.ac.za.
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7130, South Africa. christo.muller@mrc.ac.za.|Department of Biochemistry and Microbiology, University of Zululand, Kwa-Dlangezwa 3886, South Africa. christo.muller@mrc.ac.za.|Department of Medical Physiology, Stellenbosch University, Tygerberg 7507, South Africa. christo.muller@mrc.ac.za.
authors.forename: Christo
authors.initials: C
authors.lastname: Muller
mesh_terms: D000818:Animals; D036903:Aspalathus / Q000737:chemistry*; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D047188:Chalcones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000737:chemistry*; D051379:Mice; D010539:Permeability; D010936:Plant Extracts / Q000737:chemistry; D014556:Urine / Q000737:chemistry
chemical_list: D047188:Chalcones; D010936:Plant Extracts; C517016:aspalathin
keywords: Caco-2; aspalathin; bioavailability; metabolism; transport