title: Inhibitory Interactions of Aspalathus linearis (Rooibos) Extracts and Compounds, Aspalathin and Z-2-(β-d-Glucopyranosyloxy)-3-phenylpropenoic Acid, on Cytochromes Metabolizing Hypoglycemic and Hypolipidemic Drugs.
abstract: Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4, are important in the metabolism of hypoglycemic drugs, such as thiazolidinediones (TZDs) and sulfonylureas, and hypocholesterolemic drugs, such as atorvastatin. This study investigated the effects of rooibos extracts, prepared from "unfermented" and "fermented" rooibos plant material and two of the major bioactive compounds,Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG) and aspalathin (ASP), on Vivid®recombinant CYP450 enzymes. Unfermented (GRT) and fermented (FRE) rooibos extracts inhibited the activity of CYP2C8 (7.69 ± 8.85 µg/mL and 8.93 ± 8.88 µg/mL, respectively) and CYP3A4 (31.33 ± 4.69 µg/mL and 51.44 ± 4.31 µg/mL, respectively) based on their respective IC50concentrations. Both extracts dose- and time-dependently inhibited CYP2C8 activity, but only time-dependently inhibited CYP2C9. CYP3A4 showed concentration-dependent inhibition by ASP, GRT, and FRE at 25, 50, and 100 µg/mL concentrations. ASP, GRT, and FRE time-dependently inhibited CYP3A4 activity with GRT and FRE showing a more potent time-dependent inhibition, comparable to erythromycin. These findings suggest that herb-drug interactions may occur when nutraceuticals containing rooibos extracts are co-administered with hypoglycemic drugs such as TZDs, sulfonylureas, and dyslipidemic drug, atorvastatin.
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. oelfah.patel@mrc.ac.za.|Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, University of Stellenbosch, P.O. Box 241, Cape Town 8000, South Africa. oelfah.patel@mrc.ac.za.
authors.forename: Oelfah
authors.initials: O
authors.lastname: Patel
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. christo.muller@mrc.ac.za.
authors.forename: Christo
authors.initials: C
authors.lastname: Muller
authors.affiliation: Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa. JoubertL@arc.agric.za.|Department of Food Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa. JoubertL@arc.agric.za.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joubert
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. johan.louw@mrc.ac.za.
authors.forename: Johan
authors.initials: J
authors.lastname: Louw
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, University of Stellenbosch, P.O. Box 241, Cape Town 8000, South Africa. rosenkranz@sun.ac.za.
authors.forename: Bernd
authors.initials: B
authors.lastname: Rosenkranz
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. charles.awortwe@mrc.ac.za.|Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, University of Stellenbosch, P.O. Box 241, Cape Town 8000, South Africa. charles.awortwe@mrc.ac.za.
authors.forename: Charles
authors.initials: C
authors.lastname: Awortwe
mesh_terms: D036903:Aspalathus / Q000737:chemistry*; D047188:Chalcones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D041743:Herb-Drug Interactions; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D010666:Phenylpropionates / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047188:Chalcones; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D010666:Phenylpropionates; D010936:Plant Extracts; C517016:aspalathin; C035253:3-phenylpropionic acid; D003577:Cytochrome P-450 Enzyme System
keywords: ">d-glucopyranosyloxy)-3-phenylpropenoic acid; CYP2C8; CYP2C9 and CYP3A4; Z-2-(β-; aspalathin; herb-drug interaction; rooibos