Liver enzyme-mediated oxidation of Echinacea purpurea alkylamides: Production of novel metabolites and changes in immunomodulatory activity

Planta Medica

Volumn 72, Issue 15, 2006, Pages 1372-1377

  Cech, Nadja B ^a   Tutor, Katrina ^b   Doty, Bethany A ^a   Spelman, Kevin ^a,c   Sasagawa, Masa ^b,d   Raner, Gregory M ^a   Wenner, Cynthia A ^b  

^a UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

^b BASTYR UNIVERSITY   (United States)

^c Tai Sophia Institute   (United States)

^d UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Alkamides; Alkylamides; Asteraceae; Cytochrome P450; Echinacea purpurea; Interleukin 2 (IL 2); Metabolism; T lymphocytes

Indexed keywords

AMIDE; CARBOXYLIC ACID DERIVATIVE; DRUG METABOLITE; ECHINACEA PURPUREA EXTRACT; INTERLEUKIN 2; LIVER ENZYME;

ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DRUG ACTIVITY; DRUG MECHANISM; DRUG METABOLISM; DRUG OXIDATION; DRUG SCREENING; DRUG SYNTHESIS; ECHINACEA PURPUREA; HUMAN; HUMAN CELL; IMMUNOMODULATION; INCUBATION TIME; LEUKEMIA CELL LINE; LIVER MICROSOME; T LYMPHOCYTE;

CELL LINE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; ECHINACEA; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; IMMUNOLOGIC FACTORS; INTERLEUKIN-2; JURKAT CELLS; MICROSOMES, LIVER; OXIDATION-REDUCTION; PHYTOTHERAPY; PLANT EXTRACTS; POLYUNSATURATED ALKAMIDES;

ASTERACEAE; ECHINACEA (ASTERACEAE); ECHINACEA PURPUREA;

EID: 33846241704     PISSN: 00320943     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2006-951718     Document Type: Article

References (20)

1. Blumenthal M. Herb sales down 7.4 percent in mainstream market. Herbalgram 2005; 66: 63
2. Barrett B, Vohmann M, Calabrese C. Echinacea for upper respiratory infection. J Fam Pract 1999; 48: 628-35
3. Bauer R. Echinacea: Biological effects and active principles. In: Lawson LD, Bauer R, editors. Phytomedicines of Europe Washington DC: American Chemical Society, 1998: p 140-57
4. Melchart D, Linde K, Worku F, Sarkady L, Holzmann M, Jurcic K et al. Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea. J Altern Complement Med 1995; 1: 145-60
5. Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in an experimental rhinovirus infection. N Engl J Med 2005; 353: 341-8
6. Gertsch J, Schoop R, Kuenzle U, Suter A. Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Lett 2004; 577: 563-9
7. Chen Y, Fu T, Tao T, Yang J, Chang Y, Wang M et al. Macrophage activating effects of new alkamides from the roots of Echinacea species. J Nat Prod 2005; 68: 649-52
8. Raduner S, Majewska A, Chen J-Z, Xie X-Q, Hamon J, Faller B et al. Alkylamides from Echinacea are a new class of cannabinomimetics. J Biol Chem 2006; 281: 14192-206
9. Goel V, Chang C, Slama JV, Barton R, Bauer R, Gahler R et al. Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats. Int Immunopharmacol 2002; 2: 381-7
10. Sasagawa M, Cech NB, Gray DE, Elmer GW, Wenner CA. Echinacea alkylamides inhibit Interleukin-2 production by Jurkat human T cells. Int Immunopharmacol 2006; 6/7: 1214-21
11. Matthias A, Gillam EM, Penman KG, Matovic NJ, Bone KM, Voss JJD et al. Cytochrome P450 enzyme-mediated degradation of Echinacea alkylamides in human liver microsomes. Chem Biol Interact 2005; 155: 62-70
12. Coker PS, Camper ND. Bioassays of Echinacea extracts and commercial products. In: Miller SC, He-Ci, Y, editors. Echinacea: the genus Echinacea New York: CRC Press, 2004: p 181-99
13. Cech NB, Eleazer MS, Shoffner LT, Davis AC, Crosswhite MR, Mortenson AM. High performance liquid chromatography/electrospray ionization mass spectrometry for simultaneous analysis of alkylamides and caffeic acid derivatives from Echinacea purpurea extracts. J Chromatogr A 2006; 1103: 219-28
14. Matthias A, Addison RS, Penman KG, Dickinson RG, Bone KM, Lehmann RP. Echinacea alkamide disposition and pharmacokinetics in humans after tablet ingestion. Life Sci 2005; 77: 2018-29
15. He X-G, Lin L-Z, Bernart MM, Lian L-Z. Analysis of alkylamides in roots and achenes of Echinacea purpurea by liquid chromatography-electrospray mass spectrometry. J Chromatogr A 1998; 815: 205-11
16. Woelkart K, Xu W, Pei Y, Makriyannis A, Picone R, Bauer R. The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots. Planta Med 2005; 71: 701-5
17. Bouaboula M, Rinaldi M, Carayon P, Carillon C, Delpech B, Shire D et al. Cannabinoid-receptor expression in human leukocytes. Eur J Biochem 1993; 214: 173-80
18. Kaplan BLF, Ouyang Y, Herring A, Yea SS, Razdan R, Kaminski NE. Inhibition of leukocyte function and interleukin-2 gene expression by 2-methylarachidonyl-(2′-fluoroethyl)amide, a stable congener of the endogenous cannabinoid receptor ligand anandamide. Toxicol Appl Pharmacol 2005; 205: 107-15
19. Raitio KH, Salo OMH, Nevalainen T, Poso A, Jaervinen T. Targeting the cannabinoid CB2 receptor: Mutations, modeling and development of CB2 selective ligands. Current Med Chem 2005; 12: 1217-37
20. Woelkart K, Koidl C, Grisold A, Gangemi JD, Turner RB, Marth E et al. Bioavailability and pharmacokinetics of alkamides from the roots of Echinacea angustifolia in humans. J Clin Pharmacol 2005; 45: 683-9