Cytochrome P450 inhibitory action of Echinacea preparations differs widely and co-varies with alkylamide content

Echinacea preparations are one of the best selling herbal medicinal products with a well established therapeutic use in the prophylaxis of upper respiratory tract infections. Their consumption is increasing, but information about their ability to inhibit cytochrome P450 enzymes (CYP) is fragmentary. The picture is further complicated by a lack of phytochemical characterization of previously tested preparations. Due to its well characterized immunomodulatory activity, the standardized Swiss registered Echinacea purpurea (L.) Moench Echinaforce extract was selected for detailed study. With the single baculovirus-expressed CYP isoforms 1A2, 2C19, 2D9 and 3A4, inhibitory actions were measured by monitoring fluorescent metabolites derived from enzyme substrates (supersome assay). The Echinaforce extract induced mild inhibition of all these isoforms, with CYP 3A4 being the most, and CYP 2D6 the least sensitive enzyme. To assess whether CYP inhibition might be a general feature of Echinacea preparations, an additional nine commercially available preparations were screened using CYP 3A4. All tested preparations were able to inhibit CYP 3A4, but inhibitory potencies (expressed as median inhibitory concentration, IC50) varied by a factor of 150. The alkylamides are thought to be responsible for the immunomodulatory activity of Echinacea, and so the concentration of 2E,4E,8Z,10E/Z-tetranoic acid isobutylamide (1) and total alkylamide content were determined in all preparations, and the latter was found to be associated with their CYP 3A4 inhibitory potency. The chemically pure alkylamides dodeca-2E,4E,8Z,10E/Z-tetranoic acid isobutylamide (1) and dodeca-2E,4E-dieonoic acid isobutylamide (2) showed inhibitory activity on CYP 2C19, 2D6 and 3A4. However, unlike the Echinaforce extract, the alkylamides did not induce CYP 1A2 inhibition. Thus, other, as yet unidentified constituents also contribute to the overall weak inhibitory effects seen with Echinacea preparations in-vitro.

A description of the Burmese Empire

comp. chiefly from native documents by the Rev. Father Sangermano and transl. from his Ms. by William Tandy

Quarterly Journal of Science, Literature and the Arts.

1829 (July - Dec.)

Great Britain's share,

Mode of access: Internet.

[Pamphlets on banks and banking law in Great Britain.

[1] Committee of Private Country Banks. Reasons against legislative interference. 1844.--[2] Drummond, Henry. Causes which lead to a bank restriction bill. 1839.--[3] Dun, John. The English bankers' grievance and its proper remedy. 1874.--[4] Greig, J.K. Bank note and banking reform. 1880.--[5] Holdsworth, A.H. A letter to a friend in Devonshire. 1818.--[6] Kinnear, George. Banks and exchange companies. 1847.--[7] A letter to the Right Hon. the Viscount Althorp on his proposed interference with the present system of country banking. 1833.--[8] LLoyds Bank Limited. Permanent staff training. 1919.--[9] [Maclean, A.W.] Additional considerations, addressed to all classes, on the necessity and equity of a national system of deposit-banking and paper currency. 1835.--[10] Nicholson, N.A. The controversy on free banking. 1868.--[11] Steele, F.E. On changes in the bank rate. [1891]--[12] Stirling, James. Practical considerations on banks and bank management. 1865.--[13] Thoughts upon the principles of banks, and the wisdom of legislative interference. 1837.--[14] Watt, Peter. The theory and practice of joint-stock banking. 1836.

Some notes upon pharmacy as a career, including a review of the revised regulations of the Pharmaceutical Society.

Mode of access: Internet.

The physical foundation of music; being an exposition of the acoustical researches of Dr. Rudolph Kœnig of Paris.

Mode of access: Internet.

Catalogue. Supplement. Newspapers published in Great Britain and Ireland. 1801-1900.

Cover-title.

The early court of Queen Victoria,

Printed in Great Britain.

Prince consort,

Mode of access: Internet.

Queen Alexandra; a study in royalty,

Mode of access: Internet.

Report from the Select Committee on the affairs of the East India company.

Includes first-fifth reports and appendices.

Histoire de la?dministration de Lord North, ministre des finances en Angleterre, depuis 1770 jusque?n 1782, et de la guerre de l'Amérique septentrionale, jusqu'a la paix : suivie du tableau historique des finances d'Angleterre, depuis Guillaume III jusqu'en 1784.

Mode of access: Internet.

Journal of the North-China Branch of the Royal Asiatic Society for the year ...

Mode of access: Internet.

The order of keeping a court leet & court baron, with the charges appertaining to the same (1650 ed.)

By John Kitchin. - cf. Dictionary of anonymous and pseudonymous English literature, by S. Halkett and J. Laing.