Download PDF
Planta Med 2011; 77(17): 1883-1889
DOI: 10.1055/s-0031-1279990
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Chemically Characterized Fractions from Aerial Parts of Echinacea purpurea and E. angustifolia on Myelopoiesis in Rats

Sindhura Ramasahayam1 , Hany N. Baraka2 , Fatma M. Abdel Bar2 , Bilal S. Abuasal2 , Mark P. Widrlechner3 , Khalid A. El Sayed2 , Sharon A. Meyer1
  • 1Department of Toxicology, University of Louisiana at Monroe, Monroe, LA, USA
  • 2Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, Monroe, LA, USA
  • 3North Central Regional Plant Introduction Station, U. S. Department of Agriculture–Agricultural Research Service, Iowa State University, Ames, IA, USA
Further Information

Publication History

received August 11, 2010 revised January 8, 2011

accepted May 15, 2011

Publication Date:
25 August 2011 (online)

Also available at
    Permissions and Reprints

Abstract

Echinacea species are used for beneficial effects on immune function, and various prevalent phytochemicals have immunomodulatory effects. Using a commercial E. purpurea (L.) Moench product, we have evaluated the myelopoietic effect on bone marrow of rats treated with various extracts and correlated this with their chemical class composition. Granulocyte/macrophage-colony forming cells (GM-CFCs) from femurs of female Sprague-Dawley rats were assessed at 24 h after 7 daily oral treatments. A 75 % ethanolic extract at 50 mg dried weight (derived from 227 mg aerial parts) per kg body weight increased GM-CFCs by 70 % but at 100 mg/kg was without effect. Ethanolic extracts from aerial parts of E. angustifolia DC. var. angustifolia and E. purpurea from the USDA North Central Regional Plant Introduction Station increased GM-CFCs by 3- and 2-fold, respectively, at 200 mg/kg (∼ 1400 mg/kg plant material). Extract from another USDA E. angustifolia was inactive. Proton and APT NMR, MS, and TLC indicated alkylamides and caffeic-acid derivatives (CADs) present in ethanolic extracts of both the commercial and USDA-derived material. Cichoric and caftaric acids were prominent in both E. purpurea ethanolic extracts but absent in E. angustifolia. Aqueous extract of the commercial material exhibited polysaccharide and CAD signatures and was without effect on GM-CFCs. A methanol-CHCl3 fraction of commercial source, also inactive, was almost exclusively 1 : 4 nonanoic : decanoic acids, which were also abundant in commercial ethanolic extract but absent from USDA material. In conclusion, we have demonstrated an ethanol-extractable myelostimulatory activity in Echinacea aerial parts that, when obtained from commercial herbal supplements, may be antagonized by medium-chain fatty acids presumably derived from a non-plant additive.

Key words

Echinacea angustifolia - Echinacea purpurea - Asteraceae - immune function - herbal supplement - medium-chain triglyceride additive

Supporting Information

References

  • 1 Wills R B H, Bone K, Morgan M. Herbal products: active constituents, modes of action and quality control.  Nutrition Res Rev. 2000;  13 47-77
    PubMedGoogle Scholar
  • 2 Barnes J, Anderson L A, Gibbons S, Phillipson J D. Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt., Echinacea purpurea (L.) Moench): a review of their chemistry, pharmacology and clinical properties.  J Pharm Pharmacol. 2005;  57 929-954
    CrossrefPubMedGoogle Scholar
  • 3 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;  577 563-569
    CrossrefPubMedGoogle Scholar
  • 4 Chen Y, Fu T, Tao T, Yang J, Chang Y, Wang M, Kim L, Qu L, Cassady J, Scalzo R, Wang X. Macrophage activating effects of new alkamides from the roots of Echinacea species.  J Nat Prod. 2005;  68 773-776
    CrossrefPubMedGoogle Scholar
  • 5 Matthias A, Banbury L, Stevenson L M, Bone K M, Leach D N, Lehmann R P. Alkylamides from Echinacea modulate induced immune responses in macrophages.  Immunol Invest. 2007;  36 117-130
    CrossrefPubMedGoogle Scholar
  • 6 Birt D F, Widrlechner M P, Lalone C A, Wu L, Bae J, Solco A K, Kraus G A, Murphy P A, Wurtele E S, Leng Q, Hebert S C, Maury W J, Price J P. Echinacea in infection.  Am J Clin Nutr. 2008;  87 488S-492S
    PubMedGoogle Scholar
  • 7 Woelkart K, Bauer R. The role of alkamides as an active principle of Echinacea.  Planta Med. 2007;  73 615-623
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Luettig B, Steinmuller C, Gifford G E, Wagner H, Lohmann-Matthes M L. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea.  J Natl Cancer Inst. 1989;  81 669-675
    CrossrefPubMedGoogle Scholar
  • 9 Brovelli E A, Rua D, Roh-Schmidt H, Chandra A, Lamont E, Noratto G D. Human gene expression as a tool to determine horticultural maturity in a bioactive plant (Echinacea purpurea L. Moench).  J Agric Food Chem. 2005;  53 8156-8161
    CrossrefPubMedGoogle Scholar
  • 10 Hinz B, Woelkart K, Bauer R. Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells.  Biochem Biophys Res Commun. 2007;  360 441-446
    CrossrefPubMedGoogle Scholar
  • 11 Zhai Z, Solco A, Wu L, Wurtele E S, Kohut M L, Murphy P A, Cunnick J E. Echinacea increases arginase activity and has anti-inflammatory properties in RAW 264.7 macrophage cells, indicative of alternative macrophage activation.  J Ethnopharmacol. 2009;  122 76-85
    CrossrefPubMedGoogle Scholar
  • 12 Delorme D, Miller S C. Dietary consumption of Echinacea by mice afflicted with autoimmune (type I) diabetes: effect of consuming the herb on hemopoietic and immune cell dynamics.  Autoimmunity. 2005;  38 453-461
    CrossrefPubMedGoogle Scholar
  • 13 Miller S C, Sun L Z- Y. Effect of dietary administration of Echinacea on immune and hemopoietic cell lineages in murine spleen and bone marrow.  FASEB J. 1998;  12 A874
    PubMedGoogle Scholar
  • 14 Binns S E, Livesey J F, Arnason J T, Baum B R. Phytochemical variation in Echinacea from roots and flowerheads of wild and cultivated populations.  J Agric Food Chem. 2002;  50 3673-3687
    CrossrefPubMedGoogle Scholar
  • 15 Wu L, Dixon P M, Nikolau B J, Kraus G A, Widrlechner M P, Wurtele E S. Metabolic profiling of Echinacea genotypes and a test of alternative taxonomic treatments.  Planta Med. 2009;  75 178-183
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Raduner S, Majewska A, Chen J Z, Xie X Q, Hamon J, Faller B, Altmann K H, Gertsch J. Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects.  J Biol Chem. 2006;  281 14192-14206
    CrossrefPubMedGoogle Scholar
  • 17 Christensen K B, Petersen R K, Petersen S, Kristiansen K, Christensen L P. Activation of PPARgamma by metabolites from the flowers of purple coneflower (Echinacea purpurea).  J Nat Prod. 2009;  72 933-937
    CrossrefPubMedGoogle Scholar
  • 18 Spelman K, Iiams-Hauser K, Cech N B, Taylor E W, Smirnoff N, Wenner C A. Role for PPARgamma in IL-2 inhibition in T cells by Echinacea-derived undeca-2E-ene-8,10-diynoic acid isobutylamide.  Int Immunopharmacol. 2009;  9 1260-1264
    CrossrefPubMedGoogle Scholar
  • 19 Jiang S, Fu Y, Williams J, Wood J, Pandarinathan L, Avraham S, Makriyannis A, Avraham H K. Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.  PLoS ONE. 2007;  2 e641
    CrossrefPubMedGoogle Scholar
  • 20 Valk P, Verbakel S, Vankan Y, Hol S, Mancham S, Ploemacher R, Mayen A, Lowenberg B, Delwel R. Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells.  Blood. 1997;  90 1448-1457
    PubMedGoogle Scholar
  • 21 Patinkin D, Milman G, Breuer A, Fride E, Mechoulam R. Endocannabinoids as positive or negative factors in hematopoietic cell migration and differentiation.  Eur J Pharmacol. 2008;  595 1-6
    CrossrefPubMedGoogle Scholar
  • 22 Prost S, Le Dantec M, Auge S, Le Grand R, Derdouch S, Auregan G, Deglon N, Relouzat F, Aubertin A M, Maillere B, Dusanter-Fourt I, Kirszenbaum M. Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef/PPARgamma/STAT5 signaling pathway in macaques.  J Clin Invest. 2008;  118 1765-1775
    PubMedGoogle Scholar
  • 23 Woelkart K, Linde K, Bauer R. Echinacea for preventing and treating the common cold.  Planta Med. 2008;  74 633-637
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Turner R B, Bauer R, Woelkart K, Hulsey T C, Gangemi J D. An evaluation of Echinacea angustifolia in experimental rhinovirus infections.  N Engl J Med. 2005;  353 341-348
    CrossrefPubMedGoogle Scholar
  • 25 Barrett B, Brown R, Rakel D, Mundt M, Bone K, Barlow S, Ewers T. Echinacea for treating the common cold.  Ann Intern Med. 2010;  153 769-777
    CrossrefPubMedGoogle Scholar
  • 26 Heydinger J A. Physical properties of medium-chain triglycerides and application in food. In: Widlak N, editor Physical properties of fats, oils, and emulsifiers. Champaign, Il: AOCS Press; 1999: 220-225
    Google Scholar
  • 27 Frédérich M, Jansen C, de Tullio P, Tits M, Demoulin V, Angenot L. Metabolomic analysis of Echinacea spp. by 1H nuclear magnetic resonance spectrometry and multivariate data analysis technique.  Phytochem Anal. 2010;  21 61-65
    CrossrefPubMedGoogle Scholar
  • 28 Politi M, Zloh M, Pintado M, Castro P, Heinrich M, Prieto J. Direct metabolic fingerprinting of commercial herbal tinctures by nuclear magnetic resonance spectroscopy and mass spectrometry.  Phytochem Anal. 2009;  20 328-334
    CrossrefPubMedGoogle Scholar
  • 29 Tamta H, Pugh N D, Balachandran P, Moraes R, Sumiyanto J, Pasco D S. Variability in in vitro macrophage activation by commercially diverse bulk Echinacea plant material is predominantly due to bacterial lipoproteins and lipopolysaccharides.  J Agric Food Chem. 2008;  56 10552-10556
    CrossrefPubMedGoogle Scholar
  • 30 Reich E, Schibli A, DeBatt A. Validation of high-performance thin-layer chromatographic methods for the identification of botanicals in a cGMP environment.  J AOAC Intl. 2008;  91 119S-150S
    PubMedGoogle Scholar
  • 31 Kraus G A, Bae J, Wu L, Wurtele E. Synthesis and natural distribution of anti-inflammatory alkamides from Echinacea.  Molecules. 2006;  11 758-767
    CrossrefPubMedGoogle Scholar
  • 32 CAMAG .Application notes F-24A and F-24B-HPTLC. Identification of Echinacea-phenolics and alkylamides. Available at http://www.camag.com/downloads/protected/herbals/F-24a_echinacea_phenolics.pdf and /F24B_echinacea_alkylamides.pdf Accessed January 7, 2011
    Google Scholar
  • 33 Matovic N, Matthias A, Gertsch J, Raduner S, Bone K M, Lehmann R P, Devoss J J. Stereoselective synthesis, natural occurrence and CB(2) receptor binding affinities of alkylamides from herbal medicines such as Echinacea sp.  Org Biomol Chem. 2007;  5 169-174
    CrossrefPubMedGoogle Scholar
  • 34 Kale V M, Aycock M M, Wilbanks M S, Perkins E, Inouye L S, Meyer S A. Hematotoxicity of munitions compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and environmental degradation product MNX.  The Toxicologist. 2007;  96 35
    PubMedGoogle Scholar

Sharon A. Meyer, Ph.D.

Department of Toxicology
University of Louisiana at Monroe

1800 Bienville Dr

Monroe, LA 71201

USA

Phone: +1 318 3 42 16 85

Fax: +1 318 3 42 30 37

Email: meyer@ulm.edu