The effect of raspberry leaf extract on biotransformation of fluorogenic cytochrome P450 substrates by adult male rat liver microsomes

Emilija Makaji, Alison Holloway, Denis Crankshaw
McMaster University, Hamilton, Ontario, Canada

Preparations of red raspberry leaf (RRL) are widely promoted for use in pregnancy to facilitate labour. Indeed there is clinical evidence to suggest that RRL taken during pregnancy can shorten the second stage of labour (Simpson et al, 2001). Although RRL is generally considered to be safe, major questions about its pharmacokinetic effects still remain. RRL contains a number of polyphenols, a class of compounds known to affect the activity of drug metabolizing enzymes. Thus there is a potential for interaction with conventional medications and for maternal consumption of RRL to affect the subsequent development of drug metabolizing capabilities in the offspring. Therefore the goal of this study was to obtain baseline information that will help us to answer these questions by quantifying the effect of three different preparations of RRL on biotransformation of fluorogenic substrates in our standard model, adult male rat liver microsomes (Trambitas et al, 2007) and comparing these to the effects of three of the major polyphenolic constituents of RRL, ellagic acid, kaempferol and quercetin.

Raspberry herbal tea, capsules and liquid extract (40% ethanol, hereafter referred to as tincture) were obtained from local sources. Aqueous extracts of tea and capsule contents were prepared and centrifuged to remove particulate matter. These extracts, the tincture, and the pure polyphenols were then tested for effects on the biotransformation of the fluorogenic substrates 7-benzyloxy-4-(trifluoromethyl)-coumarin (BFC), 7-benzyloxyquinoline (BQ), and 7-methoxy-4-(trifuoromethyl)-coumarin (MFC) by cytochromes P450 in adult male rat liver microsomes as we have described (Trambitas et al, 2007). All RRL preparations exhibited autofluorescence at high concentrations which limited the maximum concentrations used to 250 μg/mL.

Results are given in Table 1 where all pIC50 values L are in g/mL, % rem is the per cent of enzyme activity remaining. Values are means ± s.e.mean from three experiments performed in duplicate.

We conclude that RRL has no significant direct effect on the biotransformation of these substrates in rat liver microsomes. The potential for RRL to induce drug metabolizing enzymes remains untested.

Simpson, M. et al (2001) J. Midwifery Women’s Health 46:51-59
Trambitas, C.S. et al (2007) This meeting

Supported by Sick Kids Foundation & CIHR