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Planta Med 2016; 82(01/02): 17-31
DOI: 10.1055/s-0035-1558096
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Review and Assessment of Medicinal Safety Data of Orally Used Echinacea Preparations

Karin Ardjomand-Woelkart
Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Graz, Austria
,
Rudolf Bauer
Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Graz, Austria
› Institutsangaben
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Publikationsverlauf

received 08. Februar 2015
revised 05. August 2015

accepted 14. August 2015

Publikationsdatum:
05. Oktober 2015 (online)

Auch verfügbar auf
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Abstract

Echinacea purpurea, Echinacea angustifoli and Echinacea pallida are frequently used as medicinal plants. Besides asking for evidence on their efficacy, there is an increasing interest for safety data. This review systematically presents the available literature on drug interactions, contraindications, adverse events, duration of use, and safety of use in pregnant and nursing women, and assesses the safety profile of corresponding Echinacea preparations. It is noteworthy that all safety data reported are as product specific as the pharmacological or efficacy data are. In pharmacokinetic herb-drug interaction studies performed in vivo, no significant inhibitions of human CYP2D6 and CYP3A4 isoforms have been found after the administration of standardized E. purpurea preparations. However, contradictory results exist in studies using liver microsomes. Adverse events reported during clinical trials following administration of Echinacea spp. mono-preparations were generally mild and mostly without causality. Due to published long term studies with continuous ingestion of different Echinacea preparations up to 6 month with no reported toxicological concerns, Echinacea can be recommended also for long-term use. Moreover, the contraindications in cases of autoimmune diseases and immune-suppression are questionable, since lipophilic Echinacea preparations containing alkamides suppress cellular immune responses, and beneficial effects in autoimmunity were reported. The same applies for the use during pregnancy. Although there has been some impact reported on embryonic angiogenesis in mice, no association with an increased risk for major or minor malformations during organogenesis was found in a literature review. Altogether, the different evaluated Echinacea preparations are well-tolerated herbal medicines in the management in children and adults alike.

Key words

Echinacea spp. - Asteraceae - safety
 

  • References

  • 1 Barnes J, Anderson LA, Gibbons S, Phillipson JD. 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
  • 2 Woelkart K, Bauer R. The role of alkamides as an active principle of Echinacea . Planta Med 2007; 73: 615-623
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 3 European Medicines Agency. Assessment Report on Echinacea purpurea (L.) Moench, herba recens. EMA/HMPC/557979/2013. London: European Medicines Agency; 2015
    Google Scholar
  • 4 European Medicines Agency. European Union Herbal Monograph on Echinacea purpurea (L.) Moench., herba recens. EMA/HMPC/48704/2014. London: European Medicines Agency; 2015
    Google Scholar
  • 5 European Medicines Agency. Community Herbal Monograph on Echinacea pallida (Nutt.) Nutt., radix. EMA/HMPC/332350/2008. London: European Medicines Agency; 2009
    Google Scholar
  • 6 European Medicines Agency. Community Herbal Monograph on Echinacea purpurea (L.) Moench., radix. EMA/HMPC/577784/2008. London: European Medicines Agency; 2011
    Google Scholar
  • 7 European Medicines Agency. Community List Entry on Echinacea purpurea (L.) Moench., herba recens. EMA/HMPC/189629/2007. London: European Medicines Agency; 2007
    Google Scholar
  • 8 Matthias A, Banbury LK, Stevenson LM, Bone KM, Leach DN, Lehmann RP. Alkylamides from Echinacea modulate induced immune responses in macrophages. Immunol Invest 2007; 36: 117-130
    CrossrefPubMedGoogle Scholar
  • 9 Currier NL, Miller SC. Echinacea purpurea and melatonin augment natural-killer cells in leukemic mice and prolong life span. J Altern Complement Med 2001; 7: 241-251
    CrossrefPubMedGoogle Scholar
  • 10 Currier NL, Sicotte M, Miller SC. Deleterious effects of Echinacea purpurea and melatonin on myeloid cells in mouse spleen and bone marrow. J Leukoc Biol 2001; 70: 274-276
    PubMedGoogle Scholar
  • 11 Khaksary Mahabady M, Ranjbar R, Arzi A, Papahn AA, Najafzadeh H. A comparison study of effects of Echinacea extract and levamisole on phenytoin-induced cleft palate in mice. Regul Toxicol Pharmacol 2006; 6: 163-166
    PubMedGoogle Scholar
  • 12 Mohammed Abdul MI, Jiang X, Williams KM, Day R, Roufogalis BD, Liauw WS, Xu H, Matthias A, Lehmann RP, McLachlan AJ. Pharmacokinetic and pharmacodynamic interactions of Echinacea and policosanol with warfarin in healthy subjects. Br J Clin Pharmacol 2010; 69: 508-515
    CrossrefPubMedGoogle Scholar
  • 13 Bossaer JB, Odle BL. Probable etoposide interaction with echinacea. J Diet Suppl 2012; 9: 90-95
    CrossrefPubMedGoogle Scholar
  • 14 Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000; 7: 273-282
    CrossrefPubMedGoogle Scholar
  • 15 Gorski JC, Huang S, Pinto AG, Hamman MA, Hilligoss JK, Zaheer NA, Desai MP, Miller MA, Hall SD. The effect of Echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo . Clin Pharmacol Ther 2004; 75: 89-100
    CrossrefPubMedGoogle Scholar
  • 16 Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Carrier JC, Khan IA, Edwards DJ, Shah AK. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004; 76: 428-440
    CrossrefPubMedGoogle Scholar
  • 17 Yale SH, Glurich IE. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005; 11: 433-439
    CrossrefPubMedGoogle Scholar
  • 18 Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone GW, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. Johnʼs wort, and Echinacea . Mol Nutr Food Res 2008; 52: 755-763
    CrossrefPubMedGoogle Scholar
  • 19 Moltó JM, Valle M, Miranda C, Cedeño S, Negredo E, Barbanoj MJ, Clotet B. Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother 2011; 55: 326-330
    CrossrefPubMedGoogle Scholar
  • 20 Moltó JM, Valle M, Miranda C, Cedeño S, Negredo E, Clotet B. Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients. Antimicrob Agents Chemother 2012; 56: 5328-5331
    CrossrefPubMedGoogle Scholar
  • 21 Penzak SR, Robertson SM, Hunt JD, Chairez CL, Malati CY, Alfaro RM, Stevenson JG, Kovacs JA. Echinacea purpurea significantly induces cytochrome P450 3 A activity but does not alter Lopinavir-Ritonavir exposure in healthy subjects. Pharmacotherapy 2010; 30: 797-805
    CrossrefPubMedGoogle Scholar
  • 22 Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol 2007; 100: 23-30
    CrossrefPubMedGoogle Scholar
  • 23 Hellum BH, Nilsen OG. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol 2008; 102: 466-475
    CrossrefPubMedGoogle Scholar
  • 24 Modarai M, Gertsch JÜ, Suter A, Heinrich MM, Kortenkamp A. Cytochrome P450 inhibitory action of Echinacea preparations differs widely and co-varies with alkylamide content. J Pharm Pharmacol 2007; 59: 567-573
    CrossrefPubMedGoogle Scholar
  • 25 Modarai M, Yang M, Suter A, Kortenkamp A, Heinrich MM. Metabolomic profiling of liquid Echinacea medicinal products with in vitro inhibitory effects on cytochrome P450 3A4 (CYP3A4). Planta Med 2010; 76: 378-385
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 26 Mrozikiewicz PM, Bogacz A, Karasiewicz M, Mikołajczak PL, Ozarowski M, Seremak-Mrozikiewicz A, Czerny B, Bobkiewicz-Kozłowska T, Grześkowiak E. The effect of standardized Echinacea purpurea extract on rat cytochrome P450 expression level. Phytomedicine 2010; 17: 830-833
    CrossrefPubMedGoogle Scholar
  • 27 Raner GM, Cornelious S, Moulick K, Wang Y, Mortenson AM, Cech NB. Effects of herbal products and their constituents on human cytochrome P4502E1 activity. Food Chem Toxicol 2007; 45: 2359-2365
    CrossrefPubMedGoogle Scholar
  • 28 Hansen TS, Nilsen OG. In vitro CYP3A4 metabolism: Inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition. Basic Clin Pharmacol Toxicol 2008; 103: 445-449
    CrossrefPubMedGoogle Scholar
  • 29 Kortenkamp A, Modarai M, Silva E, Suter A, Heinrich MM. Safety of herbal medicinal products: Echinacea and selected alkylamides do not induce CYP3A4 mRNA expression. Evid Based Complement Alternat Med 2011; 2011: 213021
    PubMedGoogle Scholar
  • 30 Ardjomand-Woelkart K, Kollroser M, Li L, Derendorf H, Butterweck V, Bauer R. Development and validation of a LC-MS/MS method based on a new 96-well Hybrid-SPE™-precipitation technique for quantification of CYP450 substrates/metabolites in rat plasma. Anal Bioanal Chem 2011; 400: 2371-2381
    CrossrefPubMedGoogle Scholar
  • 31 Ardjomand-Woelkart K, Kollroser M, Derendorf H, Bauer R, Butterweck V. Herb-drug interactions: effects of Echinacea preparations on cytochrome P450 activities in rats. Planta Med 2012; 78: PH10
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 32 Gertsch J. Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system. Planta Med 2008; 74: 638-650
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 33 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; 77: 563-569
    PubMedGoogle Scholar
  • 34 Raduner S, Majewska A, Chen JZ, Xie XQ, Hamon J, Faller B, Altmann KH, 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
  • 35 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
  • 36 Sasagawa M, Cech NB, Gray DE, Elmer GW, Wenner CA. Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells. Int Immunopharmacol 2006; 6: 1214-1221
    CrossrefPubMedGoogle Scholar
  • 37 Woelkart K, Marth E, Suter A, Schoop R, Raggam RB, Koidl C, Kleinhappl B, Bauer R. Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system. Int J Clin Pharmacol Ther 2006; 44: 401-408
    CrossrefPubMedGoogle Scholar
  • 38 Bauer R. Echinacea containing drugs: effects and active constituents. Z Arztl Fortbild (Jena) 1996; 90: 111-115
    PubMedGoogle Scholar
  • 39 Bauer R. Plant immunostimulating agents in self medication. Pharm Unserer Zeit 1998; 27: 144-157
    CrossrefPubMedGoogle Scholar
  • 40 Bauer VR, Jurcic K, Puhlmann J, Wagner H. [Immunological in vivo and in vitro examinations of Echinacea extracts]. Arzneimittelforschung 1988; 38: 276-281
    PubMedGoogle Scholar
  • 41 Goel V, Chang C, Slama JV, Barton R, Bauer R, Gahler R, Basu TK. Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats. Int Immunopharmacol 2002; 2: 381-387
    CrossrefPubMedGoogle Scholar
  • 42 Goel V, Chang C, Slama JV, Barton R, Bauer R, Gahler R, Basu TK. Echinacea stimulates macrophage function in the lung and spleen of normal rats. J Nutr Biochem 2002; 13: 487-492
    CrossrefPubMedGoogle Scholar
  • 43 Bodinet C, Willigmann I, Beuscher N. Host-resistance increasing activity of root extracts from Echinacea species. Planta Med 1993; 59: A672-A673
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 44 Ritchie MR, Gertsch JÜ, Klein PM, Schoop R. Effects of Echinaforce ® treatment on ex vivo-stimulated blood cells. Phytomedicine 2011; 18: 826-831
    CrossrefPubMedGoogle Scholar
  • 45 Huntley AL, Coon JT, Ernst EE. The safety of herbal medicinal products derived from Echinacea species: A systematic review. Drug Saf 2005; 28: 387-400
    CrossrefPubMedGoogle Scholar
  • 46 Miller LG. Herbal medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998; 158: 2200-2211
    CrossrefPubMedGoogle Scholar
  • 47 Ellingwood F. American materia medica, therapeutics and pharmacognosy: Ellingwoodʼs therapeutist. Chicago: Eclectic Medical Publications; 1919
    Google Scholar
  • 48 Lee AN, Werth VP. Activation of autoimmunity following use of immunostimulatory herbal supplements. Arch Dermatol 2004; 140: 723-727
    PubMedGoogle Scholar
  • 49 Logan JL, Ahmed J. Critical hypokalemic renal tubular acidosis due to Sjögrenʼs syndrome: association with the purported immune stimulant echinacea [3]. Clin Rheumatol 2003; 22: 158-159
    CrossrefPubMedGoogle Scholar
  • 50 Christensen KB, Minet AD, Svenstrup H, Grevsen K, Zhang H, Schräder EM, Rimbach GH, Wein S, Wolffram SJ, Kristiansen K, Christensen LP. Identification of plant extracts with potential antidiabetic properties: effect on human peroxisome proliferator-activated receptor (PPAR), adipocyte differentiation and insulin-stimulated glucose uptake. Phytother Res 2009; 23: 1316-1325
    CrossrefPubMedGoogle Scholar
  • 51 Christensen KB, Petersen RK, Petersen S, Kristiansen K, Christensen LP. Activation of PPARγ by metabolites from the flowers of purple coneflower (Echinacea purpurea). J Nat Prod 2009; 72: 933-937
    CrossrefPubMedGoogle Scholar
  • 52 Bone K. Echinacea: quality, uses, and immunomodulating activity from a phytotherapistʼs perspective. In: Miller SC, Yu H, editors Echinacea: the genus Echinacea . Boca Raton: CRC Press; 2004: 203-213
    Google Scholar
  • 53 See D, Broumand N, Sahl L, Tilles JG. In vitro effects of Echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology 1997; 35: 229-235
    CrossrefPubMedGoogle Scholar
  • 54 See D, Cimoch PJ, Chou S, Chang J, Tilles JG. The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Integr Physiol Behav Sci 1998; 33: 280-287
    CrossrefPubMedGoogle Scholar
  • 55 Bielory L. Adverse reactions to complementary and alternative medicine: Ragweedʼs cousin, the coneflower (Echinacea), is “a problem more than a sneeze”. Ann Allergy Asthma Immunol 2002; 88: 7-9
    CrossrefPubMedGoogle Scholar
  • 56 Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. Johnʼs wort, ginseng, Echinacea, saw palmetto, and kava. Ann Intern Med 2002; 136: 42-53
    CrossrefPubMedGoogle Scholar
  • 57 Mullins RJ. Echinacea-associated anaphylaxis. Med J Aust 1998; 168: 170-171
    PubMedGoogle Scholar
  • 58 Jeschke E, Ostermann T, Lüke C, Tabali M, Kröz M, Bockelbrink A, Witt CM, Willich SN, Matthes H. Remedies containing Asteraceae extracts: a prospective observational study of prescribing patterns and adverse drug reactions in German primary care. Drug Saf 2009; 32: 691-706
    CrossrefPubMedGoogle Scholar
  • 59 Liatsos GD, Elefsiniotis IS, Todorova R, Moulakakis AM. Erratum: Severe thrombotic thrombocytopenic purpura (TTP) induced or exacerbated by the immunostimulatory herb Echinacea . Am J Hematol 2006; 81: 722
    CrossrefPubMedGoogle Scholar
  • 60 Kemp DE, Franco KN. Possible leukopenia associated with long-term use of Echinacea . J Am Board Fam Pract 2002; 15: 417-419
    PubMedGoogle Scholar
  • 61 Goel V, Lovlin RE, Barton R, Lyon MR, Bauer R, Lee T, Basu TK. Efficacy of a standardized echinacea preparation (Echinilin™) for the treatment of the common cold: A randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther 2004; 29: 75-83
    CrossrefPubMedGoogle Scholar
  • 62 Maskatia ZK, Baker K. Hypereosinophilia associated with echinacea use. South Med J 2010; 103: 1173-1174
    CrossrefPubMedGoogle Scholar
  • 63 Lee Soon S, Crawford RI. Recurrent erythema nodosum associated with echinacea herbal therapy. J Am Acad Dermatol 2001; 44: 298-299
    CrossrefPubMedGoogle Scholar
  • 64 Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden. Pharmacoepidemiol Drug Saf 2009; 18: 1039-1047
    CrossrefPubMedGoogle Scholar
  • 65 Kocaman O, Hülagü S, Şentürk Ö. Echinacea-induced severe acute hepatitis with features of cholestatic autoimmune hepatitis. Eur J Intern Med 2008; 19: 148
    PubMedGoogle Scholar
  • 66 Barski L, Rabaev E, Sztarkier I, Delgado J, Porath A, Jotkowitz AB. Autoimmune hepatitis and hypergammaglobulinemic purpura associated with herbal medicine use. Isr Med Assoc J 2008; 10: 390-391
    PubMedGoogle Scholar
  • 67 Rusu MA, Tamaş M, Puica CD, Roman IC, Sabadas M. The hepatoprotective action of ten herbal extracts in CCl4 intoxicated liver. Phytother Res 2005; 19: 744-749
    CrossrefPubMedGoogle Scholar
  • 68 Mengs U, Clare CB, Poiley JA. Toxicity of Echinacea purpurea. Acute, subacute and genotoxicity studies. Arzneimittelforschung 1991; 41: 1076-1081
    PubMedGoogle Scholar
  • 69 Ondrizek RR, Chan P, Patton WC, King A. An alternative medicine study of herbal effects on the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid. Fertil Steril 1999; 71: 517-522
    CrossrefPubMedGoogle Scholar
  • 70 Ondrizek RR, Chan P, Patton WC, King A. Inhibition of human sperm motility by specific herbs used in alternative medicine. J Assist Reprod Genet 1999; 16: 87-91
    CrossrefPubMedGoogle Scholar
  • 71 Barcz E, Sommer E, Nartowska J, Bałan BJ, Chorostowska-Wynimko J, Skopińska-Róźewska EW. Influence of Echinacea purpurea intake during pregnancy on fetal growth and tissue angiogenic activity. Folia Histochem Cytobiol 2007; 45: 35-39
    PubMedGoogle Scholar
  • 72 Skopińska-Róźewska EW, Makuch K. Use of diet supplements, synthetic drugs and herbal remedies with immunotropic activity during pregnancy. I. Echinacea . Centr Eur J Immunol 2010; 35: 183-185
    PubMedGoogle Scholar
  • 73 Wasiutyñski AJ, Bałan BJ, Skopińska-Róźewska EW, Siwicki AK, Skurzak HM, Chorostowska-Wynimko J, Sommer E, Mazurkiewicz MX. The effect of Echinacea purpurea on the morphology, angiogenic activity and vascular endothelial growth factor (VEGF) concentration of murine L-1 sarcoma tumors. Centr Eur J Immunol 2009; 34: 38-41
    PubMedGoogle Scholar
  • 74 Perri D, Dugoua JJ, Mills EJ, Koren G. Safety and efficacy of Echinacea (Echinacea augustafolia, E. purpurea and E. pallida) during pregnancy and lactation. Can J Clin Pharmacol 2006; 13: e262-e267
    PubMedGoogle Scholar
  • 75 Gallo M, Koren G. Can herbal products be used safely during pregnancy? Focus on Echinacea . Can Fam Physician 2001; 47: 1727-1728
    PubMedGoogle Scholar
  • 76 Gallo M, Sarkar M, Au W, Pietrzak K, Comas B, Smith M, Jaeger TV, Einarson A, Koren G. Pregnancy outcome following gestational exposure to Echinacea: A prospective controlled study. Arch Intern Med 2000; 160: 3141-3143
    CrossrefPubMedGoogle Scholar
  • 77 Nordeng HM, Havnen GC. Use of herbal drugs in pregnancy. A survey among 400 Norwegian women. Pharmacoepidemiol Drug Saf 2004; 13: 371-380
    CrossrefPubMedGoogle Scholar
  • 78 Götte K, Roschke I. A supportive measure in the treatment of acute infections of the respiratory tract in children with recurring infections of the upper respiratory tract. PÄD Praktische Pädiatrie 2001; 7: 1-7
    PubMedGoogle Scholar
  • 79 Du Y, Wolf IK, Zhuang W, Bodemann S, Knöß W, Knopf H. Use of herbal medicinal products among children and adolescents in Germany. BMC Complement Altern Med 2014; 14: 218
    CrossrefPubMedGoogle Scholar
  • 80 Taylor JA, Weber WJ, Standish LJ, Quinn HC, Goesling J, McGann M, Calabrese C. Efficacy and safety of Echinacea in treating upper respiratory tract infections in children: a randomized controlled trial. JAMA 2003; 290: 2824-2830
    CrossrefPubMedGoogle Scholar
  • 81 Weber WJ, Taylor JA, Vander Stoep AV, Weiss N, Standish LJ, Calabrese C. Echinacea purpurea for prevention of upper respiratory tract infections in children. J Altern Complement Med 2005; 11: 1021-1026
    CrossrefPubMedGoogle Scholar
  • 82 Saunders PR, Smith F, Schusky RW. Echinacea purpurea L. in children: Safety, tolerability, compliance, and clinical effectiveness in upper respiratory tract infections. Can J Physiol Pharmacol 2007; 85: 1195-1199
    CrossrefPubMedGoogle Scholar
  • 83 ESCOP Monographs. The scientific foundation for herbal medicinal products. 2nd. edition. Exeter: ESCOP; 2003
    Google Scholar
  • 84 Mills S, Bone K. The essential guide to herbal safety. St. Louis, MO: Elsevier Churchill Livingstone; 2005
    Google Scholar
  • 85 Coeugniet EG, Kühnast R. [Recurrent candidiasis. Adjuvant immunotherapy with several Echinacin formulations] Rezidivierende Candidiasis. Adjuvante Immuntherapie mit verschiedenen Echinacin®-Darreichungsformen. Therapiewoche 1986; 36: 3352-3358
    PubMedGoogle Scholar
  • 86 Melchart DV, Walther E, Linde K, Brandmaier R, Lersch C. Echinacea root extracts for the prevention of upper respiratory tract infections: a double-blind, placebo-controlled randomized trial. Arch Fam Med 1998; 7: 541-545
    CrossrefPubMedGoogle Scholar
  • 87 Vonau BU, Chard S, Mandalia S, Wilkinson DM, Barton SE. Does the extract of the plant Echinacea purpurea influence the clinical course of recurrent genital herpes?. Int J STD AIDS 2001; 12: 154-158
    CrossrefPubMedGoogle Scholar
  • 88 Parnham MJ. Benefit-risk assessment of the squeezed sap of the purple coneflower (Echinacea purpurea) for long-term oral immunostimulation. Phytomedicine 1996; 3: 95-102
    CrossrefPubMedGoogle Scholar
  • 89 Jawad MS, Schoop R, Suter A, Klein PM, Eccles R. Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: A randomized, double-blind, placebo-controlled trial. Evid Based Complement Altern Med 2012; 2012
    PubMedGoogle Scholar
  • 90 Schapowal AG. Efficacy and safety of Echinaforce® in respiratory tract infections. Wien Med Wochenschr 2013; 163: 102-105
    CrossrefPubMedGoogle Scholar
  • 91 Chicca A, Pellati F, Adinolfi B, Matthias A, Massarelli I, Benvenuti S, Martinotti E, Bianucci AM, Bone K, Lehmann R, Nieri P. Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida . Br J Pharmacol 2008; 153: 879-885
    CrossrefPubMedGoogle Scholar
  • 92 Ernst E. Herbal medicinal products. Br J Gen Pract 2002; 52: 410
    PubMedGoogle Scholar
  • 93 Chow G, Johns TA, Miller SC. Dietary Echinacea purpurea during murine pregnancy: effect on maternal hemopoiesis and fetal growth. Biol Neonate 2006; 89: 133-138
    CrossrefPubMedGoogle Scholar
  • 94 Currier NL, Miller SC. The effect of immunization with killed tumor cells, with/without feeding of Echinacea purpurea in an erythroleukemic mouse model. J Altern Complement Med 2002; 8: 49-58
    CrossrefPubMedGoogle Scholar
  • 95 Sun LZ, Currier NL, Miller SC. The American coneflower: A prophylactic role involving nonspecific immunity. J Altern Complement Med 1999; 5: 437-446
    CrossrefPubMedGoogle Scholar
  • 96 Croy BA, Gambel P, Rossant J, Wegmann TG. Characterization of murine decidual natural killer (NK) cells and their relevance to the success of pregnancy. Cell Immunol 1985; 93: 315-326
    CrossrefPubMedGoogle Scholar
  • 97 De Fougerolles AR, Baines MG. Modulation of the natural killer cell activity in pregnant mice alters the spontaneous abortion rate. J Reprod Immunol 1987; 11: 147-153
    CrossrefPubMedGoogle Scholar
  • 98 Gendron RL, Baines MG. Infiltrating decidual natural killer cells are associated with spontaneous abortion in mice. Cell Immunol 1988; 113: 261-267
    CrossrefPubMedGoogle Scholar
  • 99 Lala PK, Scodras JM, Graham CH, Lysiak JJ, Parhar RS. Activation of maternal killer cells in the pregnant uterus with chronic indomethacin therapy, IL-2 therapy, or a combination therapy is associated with embryonic demise. Cell Immunol 1990; 127: 368-381
    CrossrefPubMedGoogle Scholar
  • 100 Holst L, Havnen GC, Nordeng HM. Echinacea and elderberry-should they be used against upper respiratory tract infections during pregnancy?. Front Pharmacol 2014; 5: 31
    PubMedGoogle Scholar
  • 101 Morazzoni P, Cristoni A, Di Pierro F, Avanzini C, Ravarino D, Stornello SL, Zucca M, Musso T. In vitro and in vivo immune stimulating effects of a new standardized Echinacea angustifolia root extract (Polinacea™). Fitoterapia 2005; 76: 401-411
    CrossrefPubMedGoogle Scholar
  • 102 EMA. Guideline on the Investigation of Drug Interactions. European Medicines Agency – Science Medicines Health. Committee for Human Medicinal Products (CHMP); 2012
    Google Scholar
  • 103 FDA. Drug Interaction Studies – Study Design, Data Analysis Implications for Dosing, and Labeling Recommendations. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). 2012
    Google Scholar
  • 104 Schapowal AG, Berger DS, Klein PM, Suter A. Echinacea/sage or chlorhexidine/lidocaine for treating acute sore throats: a randomized double-blind trial. Eur J Med Res 2009; 14: 406-412
    CrossrefPubMedGoogle Scholar
  • 105 Hill LL, Foote JC, Erickson BD, Cerniglia CE, Denny GS. Echinacea purpurea supplementation stimulates select groups of human gastrointestinal tract microbiota. J Clin Pharm Ther 2006; 31: 599-604
    CrossrefPubMedGoogle Scholar
  • 106 See D, Berman S, Justis J, Broumand N, Chou S, Chang J, Tilles J. A phase I study on the safety of Echinacea angutifolia and its effect on viral load in HIV infected individuals. J Am Nutr Assoc (JANA) 1998; 1: 14-17
    PubMedGoogle Scholar
  • 107 Grimm W, Müller HH. A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infections. Am J Med 1999; 106: 138-143
    CrossrefPubMedGoogle Scholar
  • 108 Brinkeborn RM, Shah DV, Degenring FH. Echinaforce® and other Echinacea fresh plant preparations in the treatment of the common cold: a randomized, placebo controlled, double-blind clinical trial. Phytomedicine 1999; 6: 1-6
    CrossrefPubMedGoogle Scholar
  • 109 Gallo MA, Sarkar M, Au W, Pietrzak K, Comas B, Smith MJ, Jaeger TV, Einarson AR, Koren G. Pregnancy outcome following gestational exposure to echinacea: a prospective controlled study. Arch Intern Med 2000; 160: 3141-3143
    CrossrefPubMedGoogle Scholar
  • 110 Schulten B, Bulitta M, Ballering-Brühl B, Köster U, Schäfer M. Efficacy of Echinacea purpurea in patients with a common cold: A placebo-controlled, randomised, double-blind clinical trial. Arzneimittelforschung 2001; 51: 563-568
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 111 Rostock M, Mumm A, Unger C. [Application of medicinal plants in oncology] Die Anwendung von Arzneipflanzen in der Onkologie. Z Allgemeinmed 1998; 74: 1163-1168
    PubMedGoogle Scholar
  • 112 Kim L, Waters RF, Burkholder PM. Immunological activity of larch arabinogalactan and Echinacea: A preliminary, randomized, double-blind, placebo-controlled trial. Altern Med Rev 2002; 7: 138-149
    PubMedGoogle Scholar
  • 113 Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, DʼAlessio DJ. Treatment of the common cold with unrefined Echinacea: A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2002; 137: 939-946
    CrossrefPubMedGoogle Scholar
  • 114 Lindenmuth GF, Lindenmuth EB. The efficacy of Echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: A randomized, double-blind placebo-controlled study. J Altern Complement Med 2000; 6: 327-334
    CrossrefPubMedGoogle Scholar
  • 115 Turner RB, Riker DK, Gangemi JD. Ineffectiveness of Echinacea for prevention of experimental rhinovirus colds. Antimicrob Agents Chemother 2000; 44: 1708-1709
    CrossrefPubMedGoogle Scholar
  • 116 Sperber SJ, Shah LP, Gilbert RD, Ritchey TW, Monto AS. Echinacea purpurea for prevention of experimental rhinovirus colds. Clin Infect Dis 2004; 38: 1367-1371
    CrossrefPubMedGoogle Scholar
  • 117 Yale SH, Liu K. Echinacea purpurea therapy for the treatment of the common cold: A randomized, double-blind, placebo-controlled clinical trial. Arch Intern Med 2004; 164: 1237-1241
    CrossrefPubMedGoogle Scholar
  • 118 Goel V, Lovlin RE, Chang C, Slama JY, Barton R, Gahler RJ, Bauer R, Goonewardene LA, Basu TK. A proprietary extract from the Echinacea plant (Echinacea purpurea) enhances systemic immune response during a common cold. Phytother Res 2005; 19: 689-694
    CrossrefPubMedGoogle Scholar
  • 119 Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med 2005; 353: 341-348
    CrossrefPubMedGoogle Scholar
  • 120 Hall HL, Fahlman MM, Engels HJ. Echinacea purpurea and mucosal immunity. Int J Sports Med 2007; 28: 792-797
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 121 OʼNeil J, Hughes SM, Lourie A, Zweifler JA. Effects of Echinacea on the frequency of upper respiratory tract symptoms: a randomized, double-blind, placebo-controlled trial. Ann Allergy Asthma Immunol 2008; 100: 384-388
    CrossrefPubMedGoogle Scholar
  • 122 Barrett BP, Brown RL, Rakel DP, Rabago DP, Marchand LR, Scheder J, Mundt MP, Thomas GR, Barlow SK. Placebo effects and the common cold: A randomized controlled trial. Ann Fam Med 2011; 9: 312-322
    CrossrefPubMedGoogle Scholar
  • 123 Tiralongo E, Lea RA, Wee S, Hanna M, Griffiths LR. Randomised, double blind, placebo-controlled trial of Echinacea supplementation in air travellers. Evid Based Complement Alternat Med 2012; 2012: 417267
    PubMedGoogle Scholar