title: The potential of Hypoxis hemerocallidea for herb-drug interaction.
abstract: BACKGROUND
  Aqueous decoction of Hypoxis hemerocallidea Fisch. & C.A. Mey. (Hypoxidaceae) (Hypoxis) is widely consumed in Southern Africa by people living with HIV/AIDS, some of whom are on ARV and other medications.
  
  
  OBJECTIVE
  The aim of this study was to investigate the potential of the crude aqueous extracts of Hypoxis to inhibit major forms of CYP450 and transport proteins.
  
  
  METHODS
  Corms of Hypoxis were water-extracted and incubated (in graded concentrations: 1-100 µg/mL) with human liver microsomes (20 min) to monitor the effects on phenacetin O-deethylation, coumarin 7-hydroxylation, bupropion hydroxylation, paclitaxel 6α-hydroxylation, diclofenac 4'-hydroxylation, S-mephenytoin 4'-hydroxylation, bufuralol 1'-hydroxylation, chlorzoxazone 6-hydroxylation, midazolam 1'-hydroxylation and testosterone 6β-hydroxylation as markers for the metabolic activities of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4/5, respectively. The generation of metabolites were monitored and quantified with the aid of LC-MS/MS. The potential of the extracts to inhibit human ATP-binding cassette transporter activity was assessed using recombinant MDCKII and LLC-PK1 cells over-expressing human breast cancer resistant protein and human P-glycoprotein , respectively (with Ko143 and cyclosporin A as positive controls). Similar assessment was performed with human organic anion transporting polypeptide (OATP1B1 and OATP1B3) using recombinant HEK293 cells over-expressing OATP1B1 and OATP1B3, respectively (with rifamycin and 10 µM atorvastatin as positive controls).
  
  
  RESULTS
  Extracts of Hypoxis inhibited the production of the metabolites of the substrates of the following enzymes (as compared to controls) with the indicated IC50 values (µg/mL): CYP1A2 (120.6), CYP2A6 (210.8), CYP2B6 (98.5), CYP2C8 (195.2), CYP2C9 (156) and CYP3A4/5 (185.4). The inhibition of the uptake activity of OATP1B1 and OATP1B3 were also observed with IC50 values of 93.4 and 244.8 μg/mL, respectively.
  
  
  CONCLUSIONS
  Extract concentrations higher than the estimated IC50 values are achievable in the gastrointestinal tract when traditional doses of Hypoxis are considered. This may have profound effects on presystemic metabolism of the drug substrates. If absorbed, systemic inhibition of metabolic enzymes/transporters by Hypoxis may be expected.
  
  
  CONCLUSIONS
  The result suggests that there is the potential for HDI between Hypoxis and the substrates of the affected enzymes/transporters, if sufficient in vivo concentration of Hypoxis extracts is attained.
authors.affiliation: Division of Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch , Cape Town , South Africa .
authors.forename: Pius S
authors.initials: PS
authors.lastname: Fasinu
authors.forename: Heike
authors.initials: H
authors.lastname: Gutmann
authors.forename: Hilmar
authors.initials: H
authors.lastname: Schiller
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bouic
authors.forename: Bernd
authors.initials: B
authors.lastname: Rosenkranz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D004285:Dogs; D057809:HEK293 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D027802:Hypoxis / Q000737:chemistry*; D066298:In Vitro Techniques; D018374:LLC-PK1 Cells; D061985:Madin Darby Canine Kidney Cells; D016488:Medicine, African Traditional; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D004364:Pharmaceutical Preparations; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D013379:Substrate Specificity; D013552:Swine
chemical_list: D018528:ATP-Binding Cassette Transporters; D065607:Cytochrome P-450 Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D010936:Plant Extracts