Intestinal Transport Characteristics and Metabolism of C-Glucosyl Dihydrochalcone, Aspalathin
Sandra Bowles,
Elizabeth Joubert,
Dalene de Beer,
Johan Louw,
Christel Brunschwig,
Mathew Njoroge,
Nina Lawrence,
Lubbe Wiesner,
Kelly Chibale,
Christo Muller
Affiliations
Sandra Bowles
Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7130, South Africa
Elizabeth Joubert
Plant Bioactives Group, Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Stellenbosch 7600, South Africa
Dalene de Beer
Plant Bioactives Group, Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Stellenbosch 7600, South Africa
Johan Louw
Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7130, South Africa
Christel Brunschwig
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Mathew Njoroge
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Nina Lawrence
Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa
Lubbe Wiesner
Division of Clinical Pharmacology, University of Cape Town, Observatory, Cape Town 7925, South Africa
Kelly Chibale
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Christo Muller
Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7130, South Africa
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 × 10−6 cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1.84 × 10−6 cm/s; efflux ratio: 1.1) were excluded as primary transporters, since the Papp of aspalathin was not affected by the presence of specific inhibitors. The Papp of 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 Papp value to 2.9 × 10−7 cm/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.
