Nair V.D.P., Foster B.C., Thor Arnason J., Mills E.J., Kanfer I.
Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa; Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, Ont., Canada; The Canadian College of Naturopathic Medicine, Toronto, Ont., Canada
Nair, V.D.P., Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa; Foster, B.C., Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, Ont., Canada; Thor Arnason, J., Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, Ont., Canada; Mills, E.J., The Canadian College of Naturopathic Medicine, Toronto, Ont., Canada; Kanfer, I., Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa
African potato (Hypoxis hemerocallidea, AP) is a traditional herbal medicine widely used as an immune booster and also for the treatment of various ailments such as urinary diseases, prostrate hypertrophy and cancer. Amongst the chemical components contained in AP, the norlignan glycoside, hypoxoside (HYP) is purported to be the most important phytochemical in terms of AP's medicinal value. Additional constituents in AP include the sterols, β-sitosterol (BSS), stigmasterol (STG), and the stanol, stigmastanol (STN). The potential of extracts of AP, AP formulations as well as HYP, its aglycone rooperol (ROP) and the sterols to inhibit in vitro metabolism of drug marker substrates by human cytochrome P450 (CYP) enzymes such as CYP3A4, 3A5 and CYP19 were investigated. Samples were also assessed for their effect on drug transport proteins such as P-glycoprotein (P-gp). The effects on CYP-mediated metabolism were studied by fluorometric microtitre plate assay. The potential interaction with P-gp was investigated by measuring the efflux of the fluorescent dye rhodamine 123 (Rh 123) in the CaCo-2 (colon carcinoma) cell line. Various extracts of AP, AP formulations, only STG and the norlignans, in particular the aglycone ROP, exhibited inhibitory effects on CYP3A4-, 3A5- and 19-mediated metabolism. The extracts and the formulations that contained a significant amount of HYP showed high induction of P-gp compared to the positive control, ritonavir. Whilst extrapolation of the current in vitro findings to clinical effects may well be considered speculative, these in vitro data should be heeded as a signal of possible in vivo interactions. Appropriate measures are therefore necessary to explore the possibility of such in vitro-in vivo correlations. © 2007 Elsevier GmbH. All rights reserved.
African potato extract; alpha tocopherol; aromatase; ascorbic acid; cyanocobalamin; cytochrome P450; cytochrome P450 3A4; cytochrome P450 3A5; fluorescent dye; ginseng extract; glycoprotein P; hypoxoside; norlignan glycoside; plant extract; plant medicinal product; pyridoxine; retinol; rhodamine 123; riboflavin; ritonavir; rooperol; selenium; sitostanol; sitosterol; stanol ester; sterol derivative; stigmasterol; thiamine; unclassified drug; unindexed drug; vitamin D; article; cell strain CACO 2; controlled study; drug formulation; drug metabolism; herb; human; human cell; in vitro study; in vivo study; nonhuman; potato; priority journal; protein induction; traditional medicine; Caco-2 Cells; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Hypoxis; Molecular Structure; P-Glycoprotein; Plant Extracts; Ritonavir; Hypoxis hemerocallidea; Solanum tuberosum