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The potential of Hypoxis hemerocallidea for herb-drug interaction.
Pharm Biol. 2013 Dec; 51(12):1499-507.PB

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 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.

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.

Authors+Show Affiliations

Division of Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch , Cape Town , South Africa .No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23844611

Citation

Fasinu, Pius S., et al. "The Potential of Hypoxis Hemerocallidea for Herb-drug Interaction." Pharmaceutical Biology, vol. 51, no. 12, 2013, pp. 1499-507.
Fasinu PS, Gutmann H, Schiller H, et al. The potential of Hypoxis hemerocallidea for herb-drug interaction. Pharm Biol. 2013;51(12):1499-507.
Fasinu, P. S., Gutmann, H., Schiller, H., Bouic, P. J., & Rosenkranz, B. (2013). The potential of Hypoxis hemerocallidea for herb-drug interaction. Pharmaceutical Biology, 51(12), 1499-507. https://doi.org/10.3109/13880209.2013.796393
Fasinu PS, et al. The Potential of Hypoxis Hemerocallidea for Herb-drug Interaction. Pharm Biol. 2013;51(12):1499-507. PubMed PMID: 23844611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The potential of Hypoxis hemerocallidea for herb-drug interaction. AU - Fasinu,Pius S, AU - Gutmann,Heike, AU - Schiller,Hilmar, AU - Bouic,Patrick J, AU - Rosenkranz,Bernd, Y1 - 2013/07/11/ PY - 2013/7/13/entrez PY - 2013/7/13/pubmed PY - 2014/6/11/medline SP - 1499 EP - 507 JF - Pharmaceutical biology JO - Pharm Biol VL - 51 IS - 12 N2 - 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 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. 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. SN - 1744-5116 UR - https://www.unboundmedicine.com/medline/citation/23844611/The_potential_of_Hypoxis_hemerocallidea_for_herb_drug_interaction_ L2 - https://www.tandfonline.com/doi/full/10.3109/13880209.2013.796393 DB - PRIME DP - Unbound Medicine ER -