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Herbal tea extracts inhibit Cytochrome P450 3A4 in vitro.

The Journal of pharmacy and pharmacology (2014-05-16)
Sophie Dufay, Alan Worsley, Aymeric Monteillier, Charlotte Avanzi, Jaclyn Sy, Ting Fat Ng, Jean-Michel Garcia, Man-Fai Lam, Paul Vanhoutte, Ian C K Wong
ABSTRACT

Ciclosporin and sirolimus, two immunosuppressive agents with narrow therapeutic windows, are mainly metabolized by Cytochrome 3A4 (CYP3A4). A clinical case of toxic blood levels of these drugs after the consumption of a '24-flavours' tea was reported. This study aims to identify the causative ingredients of the 24-flavour herbal tea in the inhibition of CYP3A4 metabolism. Two commercially available 24-flavour tea products purchased in Hong Kong and the six plant constituents were tested for their CYP3A4 inhibitory effects utilizing an in-vitro fluorometric assay. Of the commercially available teas available in Hong Kong, the most potent inhibitory effect was observed with the tea consumed in the initial clinical case. Of the six universal constituents, chrysanthemum exhibited the greatest inhibitory effect, with an IC50 of 95.7 μg/ml. Dandelion, liquorice and bishop's weed have IC50 of 140.6, 148.4 and 185.5 μg/ml, respectively. Field mint and Japanese honeysuckle have weaker inhibitory effect on CYP3A4 with IC50 of 1153.3 and 1466.3 μg/ml. This study confirms the possible implication of herbal tea constituents in the inhibition of ciclosporin and sirolimus' CYP3A4 metabolism. Combined usage of herbal teas with drug should be closely monitored.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(±)-Naringenin, ≥95%
Sigma-Aldrich
Glycyrrhizic acid ammonium salt from glycyrrhiza root (licorice), ≥95.0% (NT)
Sigma-Aldrich
Naringenin, natural (US), 98%
Supelco
Glycyrrhizic acid ammonium salt, analytical standard, suitable for HPLC
Supelco
(±)-Naringenin, analytical standard
Supelco
Quercetin, Pharmaceutical Secondary Standard; Certified Reference Material
Ammonium glycyrrhizate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Quercetin, ≥95% (HPLC), solid
Sigma-Aldrich
Glycyrrhizic acid ammonium salt from glycyrrhiza root (licorice), ≥70% (HPLC)
USP
Quercetin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Hesperidin, ≥80% (HPLC)
Sigma-Aldrich
Ursolic acid, ≥90%
Sigma-Aldrich
Oleanolic acid, ≥97%
Supelco
Ursolic acid, analytical standard
Glycyrrhizate monoammonium, European Pharmacopoeia (EP) Reference Standard
Hesperidin, European Pharmacopoeia (EP) Reference Standard
Supelco
Oleanolic acid, analytical standard
Ursolic acid, primary reference standard
Hesperidin, primary reference standard
Supelco
Hesperidin, analytical standard
Ursolic acid, European Pharmacopoeia (EP) Reference Standard