Planta Med 2006; 72 - P_290
DOI: 10.1055/s-2006-950090

Echinacea and its alkamides – an assessment of potential CYP-P450 enzyme inhibition?

M Modarai 1, J Gertsch 2, A Suter 3, A Kortenkamp 1, M Heinrich 1
  • 1The School of Pharmacy University of London29/39 Brunswick Square London WC1N 1AX United Kingdom
  • 2Department of Chemistry and Applied Biosciences, Office HCI H494.4, Wolfgang-Pauli-Str. 10, ETH Hönggerberg CH-8093 Zürich Switzerland
  • 3Bioforce AG, 9325 Roggwil, Switzerland

Echinacea is a top selling HMP, yet there is still limited and unclear information regarding possible interactions between Echinacea and other concurrent medicines. The objective was to analyse the inhibitory potential of the standardised Echinacea extract (Echinaforce®) and two alkamides: dodeca 2E,4E,8Z,10E/Z tetraenoic acid isobutylamide (TAI) and dodeca 2E,4E-dienoic acid isobutylamide (DAI) on single baculovirus expressed Cytochrome P450 isoforms – CYP1A2, CYP2C19, CYP2D6 and CYP3A4 as stipulated by the German regulatory authority BfArM (Bundesinstitut fur Arzneimittel und Medizinprodukte) [1].

In a modified fluorometric 96-well plate assay enzyme activity was measured by detecting the fluorescent metabolite produced from the reaction of the substrate with the CYPs [2]. The substrates used were 7-BFC (CYP3A4), CEC (CYP1A2, CYP2C19) and AMMC (CYP2D6). Control reactions were also set up to account for intrinsic fluorescence of the extract and the effect of ethanol on the enzyme.

The extract and its alkamides showed moderate inhibitory activity against CYP enzymes, but these effects are unlikely at the doses of Echinaforce® normally encountered in clinical setting (Table). The lowest IC50 value recorded in our study was 1.96µg/mL for TAI. Based upon a recent bioavailability study, these values would be 4900 folds higher than the anticipated maximal concentration in hepatocytes, assuming that there are no potential losses of the alkamide via distribution, uptake etc [3]. With these IC50 values it is unlikely that inhibitory concentrations will be reached within the liver.

Table: Median inhibitory concentrations (IC50) and the upper and lower 95% confidence limits (depicted in brackets) for Echinaforce® and alkamides against CYP isoforms.

CYP1A2

CYP2C19

CYP2D6

CYP3A4

Echinaforce®(µg/mL)

26.54 (23.81–29.57)

53.47 (32.30–88.79)

60.97 (50.29–73.91)

19.49 (18.80–20.20)

DAI (µg/mL)

No inhibition

23.35 (17.37–31.40)

10.10 (7.209–14.151)

5.17 (4.11–6.52)

TAI (µg/mL)

No inhibition

18.91 (14.86–24.05)

6.76 (5.21–8.77)

1.91 (1.74–2.09)

Acknowledgements: Bioforce UK for funding this project.

References: 1. http://www.bfarm.de/cln_042/nn_424630/DE/Arzneimittel/besTherap/amPflanz/

ampflanz-node.html. 2. Crespi, C.L. et al. (1997) Analytical Biochemistry 248: 188–190. 3. Bauer, R. et al. (2005) Presentation, GA conference, Florence.