The effects of herbals for women on the biotransformation of fluorogenic substrates by human cytochromes P450

Mohini Singh, Alison C Holloway, Denis J Crankshaw

McMaster University, Hamilton, ON, Canada

Herbal preparations of Black Cohosh root (Actaea racemosa, BC), Chaste Tree Berry (Vitex agnus-castus, CTB), Crampbark (Viburnum opulus, CBK) and False Unicorn (Chamaelirium luteum, FU) are widely promoted as a natural method to relieve menopausal and premenstrual symptoms. Natural products are often thought to be a safe alternative to pharmaceuticals, yet many women take both herbals and prescription medications at the same time. Some herbal preparations have the ability to inhibit the drug metabolizing enzymes, cytochromes P450 (CYP), and the simultaneous administration of herbals and pharmaceuticals can lead to adverse drug reactions (Fugh-Berman & Ernst, 2001). To test for the possibility of herb/drug interactions we have quantified the effect of one preparation each of BC, CTB, CBK and FU on the biotransformation of fluorogenic substrates by recombinant human CYPs.

Commercial liquid extracts of BC and CTB (Gaia Herbs) and CBK and FU (St Francis Farms) were obtained from local sources. These extracts were then tested for effects on the biotransformation of 7-ethoxyresorufin by CYP1A1, 3-cyano-7-ethoxycoumarin by CYP1A2 & CYP2C19, 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin by CYP2D6, and 7-benzyloxyquinoline by CYP3A4, as described by Ho et al (2007). Incubations of human CYPs with substrates were performed under linear conditions at 37ºC in the presence of an NADPH regenerating system in black 96-well plates. The formation of product was monitored kinetically by measurement of fluorescence intensity at the appropriate wavelengths. All four herbals exhibited either autofluorescence or fluorescence quenching which limited the maximum concentrations that could be used. Effects were expressed as the negative log of the concentration in g/mL that produced 50% inhibition (pIC50).

Results are given in Table 1, where values are means ± s.e.mean of 3 - 6 experiments performed in triplicate. None of the preparations affected the activity of CYP1A1.

We conclude that all of the four herbals are poor to moderate inhibitors of some of the CYPs that we investigated. Depending on the bioavailability of the active components, moderate consumption may provoke adverse drug reactions by inhibiting biotransformations involving these particular enzymes.

Supported by SickKids Foundation & Canadian Institutes of Health Research

Fugh-Berman, A & Ernst, E (2001) Br.J.Clin.Pharmacol 52:587

Ho, S. et al (2007) BPS winter meeting http://www.pa2online.org/abstracts/Vol5Issue2abst083P.pdf