Metabolomic profiling of liquid Echinacea medicinal products with in vitro inhibitory effects on cytochrome P450 3A4 (CYP3A4).

Modarai, M., Yang, M., Suter, A., Kortenkamp, A. and Heinrich, M. (2010) Metabolomic profiling of liquid Echinacea medicinal products with in vitro inhibitory effects on cytochrome P450 3A4 (CYP3A4). Planta Medica, 76 (4). pp. 378-385. 10.1055/s-0029-1186152.

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DOI: 10.1055/s-0029-1186152

Abstract

ECHINACEA is a popular and widely used herbal medicinal product and consequently, studies of its interactions with conventional drugs are of particular importance. We have shown that ECHINACEA preparations and some common alkylamides weakly inhibit several cytochrome P450 (CYP) isoforms, with considerable variation in potency. We now report a detailed analysis of six commercial ECHINACEA liquid preparations, with emphasis on the metabolomic characterisation of the ECHINACEA compounds responsible for inhibiting CYP3A4. We separated each preparation into its ethanol- and water-soluble components, and then used (1)H-NMR together with multivariate data analysis and partial least square regression analysis to investigate the nature of the compounds responsible for CYP3A4 inhibition. The results implicated alkylamides in the CYP3A4 inhibitory activity of ECHINACEA. One of the commercial preparations (Echinaforce(R)) was further fractionated using solid phase extraction. Analysis by (1)H-NMR and mass spectroscopy (LC/MS, tandem MS, accurate mass) identified dodeca-2 E,4 E,8 Z,10 E/Z-tetraenoic acid (alkylamide 1) and a new compound (putative molecular formula C (18)H (36) NO (+)) as major components of the inhibitory fractions. In addition, the alkylamide content of all six preparations was determined by reverse phase HPLC. Levels of alkylamides 1 and 3 (undeca-2 E,4 E/ Z-diene-8,10-diynoic acid isobutylamide), correlated well with CYP3A4 inhibition. The acetylene tetradeca-8 Z-ene-11,13-diyn-2-one was shown to be present in the E. PURPUREA as well as the E. PALLIDA extracts. E. PURPUREA unlike E. PALLIDA was thought to not contain significant amounts of acetylenes. Our results directly confirm the role of alkylamides in the inhibition of CYP3A4 by ECHINACEA and uncovered a new compound which may also be involved. Extensive differences in the composition of the commercially available preparations were found. This will inevitably impact on the product efficacy, safety and pharmacological effects, especially since the differences involve alkylamides, an important class of ECHINACEA's active constituents. The metabolomic approach presented here may prove valuable as a screening or quality control tool.

Item Type:Article
Additional Information:Full text available in print from the School of Pharmacy Library.
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Centre for Pharmacognosy and Phytotherapy
ID Code:1539
Journal or Publication Title:Planta Medica
Deposited By:Library Staff
Deposited On:16 Apr 2010 09:55
Last Modified:07 Oct 2011 15:56

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