The potential of Hypoxis hemerocallidea for herb-drug interaction
Date
2013
Journal Title
Journal ISSN
Volume Title
Publisher
Informa Healthcare
Abstract
Context: 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.
Materials and methods: Corms of Hypoxis were water-extracted and incubated (in graded
concentrations: 1–100 mg/mL) with human liver microsomes (20 min) to monitor the effects
on phenacetin O-deethylation, coumarin 7-hydroxylation, bupropion hydroxylation, paclitaxel
6a-hydroxylation, diclofenac 40
-hydroxylation, S-mephenytoin 40
-hydroxylation, bufuralol
10
-hydroxylation, chlorzoxazone 6-hydroxylation, midazolam 10
-hydroxylation and testosterone
6b-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 ATPbinding 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 mM
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 (mg/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 mg/mL, respectively.
Discussion: 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.
Conclusion: 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.
Description
CITATION: Fasinu, P. S. et al. 2013. The potential of Hypoxis hemerocallidea for herb-drug interaction. Pharmaceutical Biology, 51(12):1499-1507, doi:10.3109/13880209.2013.796393.
The original publication is available at https://www.tandfonline.com
The original publication is available at https://www.tandfonline.com
Keywords
Hypoxis hemerocallidea, Antiretroviral agents, Drugs -- Metabolism, Traditional medicine
Citation
Fasinu, P. S. et al. 2013. The potential of Hypoxis hemerocallidea for herb-drug interaction. Pharmaceutical Biology, 51(12):1499-1507, doi:10.3109/13880209.2013.796393.