Abstract
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 2
E
,4
E
,8
Z
,10
E
/
Z
tetraenoic acid isobutylamide (TAI) and dodeca 2
E
,4
E
-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 IC
50
values it is unlikely that inhibitory concentrations will be reached within the liver.
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.