Echinacea species

ECHINACEA PURPUREA (L.) ­MOENCH / ECHINACEA ANGUSTIFOLIA DC. / Rode zonnehoed
monografie uit het cursusboek van de herboristen opleiding 'Dodonaeus' samengesteld door Maurice Godefridi

Algemene en Botanische Informatie

Familie: Asteraceae (Compositae) - Samengesteldbloemi­gen.
Naam: Kegelblume (D.), Coneflower (E.), Rode zonnehoed.
Naamverklaring: Grieks 'echinos' = Egel.
Enkele soorten:
  • E. purpurea,
  • E. purpurea c.v. The King,
  • E. angustifolia var. angustifolia,
  • E. pallida (NULT.) NUTT.
9 soorten en 2 variëteiten volgens Mc. Gregor Univ. Kansas - Sci. Bull. 48/113-142
Ecologie, teelt: Afkomstig uit de USA (o.a. Ohio) gebruikt door de Indianen in Noord Amerika
Vaste plant, gemakkelijk te zaaien en te scheuren.

Materia medica, gebruikte delen van de plant

Echinaceae radix - Echinaceae herba,  De hele bovengrondse bloeiende plant van E. purpurea, E. angustifolia en E. pallida of de wortel van vooral  E. angustifolia
  • Oogst: De wortel in de herfst of het voorjaar. Het kruid tijdens de vroege bloei.
  • Geur: Zwak aromatisch.
  • Smaak: Van zoet tot scherp bitter. Het proeven vermeerdert de speekselsecretie en veroorzaakt een prikkelend effect op de tong (alkylamiden)
  • Vervalsing: Parthenium integrifolium L. (verschil: wortel is zwart gekleurd en heeft knolvormige hoofdwor­tel)
Samenstelling, inhoudstoffen

** Echinacoside (bacteriostatisch werkend glucoside (3)
** Polysacchariden met selectieve werking op macrofagen en granulocyten (1, 2), zetten macrofagen aan tot een grotere cytotoxiteit tegen sommige tumorcellen.
** Cichoreizuur e.a. (immuunmodulerend effect).
* Etherische olie 1,25 %.
** Isobutylamide (o.a. echinaceïn), polyinen (stimuleren de fagocytose)
* Vitamine C
* Inuline 5-9 %, Suikers: glucose 7 %, fructose 4 %
* Betaïne
* Fytosterolen
Nota: Er is veel onderzoek verricht vooral naar de immuunmodulerende eigen­schappen

Farmacologie, algemene fysiologische werking

** Immuunmodulerend effect.
Verhoogt onrechtstreeks de natuur­lijke af­weerkrachten; daaruit volgt een bacteriostatisch en een virussta­tisch effect. Wordt veroor­zaakt door interferon­achtige werking. Interferon ontstaat in het organisme als reactie op een virusin­fectie. Interferon stimuleert de aanmaak van een proteïne tegen virussen.
Inhiberend (remmend) effect op hyaluronidase (4). Hyaluroni­dase ontbindt hyaluronzuur dat het hoofdbestanddeel is van de steunweefsels en capillair­wanden. Hyaluronzuur vormt samen met proteïne een mechanische bescherming tegen het binnen­drin­gen van bacteriën.
Stimulatie aanmaak van leucocyten (witte bloedcellen) en tengevolge daarvan meer fagocy­tose. Stimuleert ook de lymfecircula­tie.
* Speeksel- en transpiratie-opwekkend (vers).
** Wondgenezend (regeneratie gezond granulatieweefsel).
* Afrodisiacum ?

Indicatie, medicinaal gebruik van Echinacea species

Luchtwegen en Infecties
** Virusinfecties (preventief en curatief): verkoudheid, griep, herpes simplex (+ Ravensara aromatica e.o)
** Chronische ontstekingen vooral luchtwegen: na veelvuldig antibioticagebruik, bij gebrek aan weerstand.
       vooral bij keelpijn, amandelontsteking, sinusitis zie ook Salvia, Eucalptus e.a.

Lymfestelsel
* Lymfangitis (bloedvergiftiging)
* Opgezette, verharde lymfeklieren ook Schrophularia nodosa e.a.
* Ziekte van Pfeiffer (klierkoorts)

Klierstelsel
** Prostatitis zie prostaatplanten: Serenoa, Urtica..

Huid (antisepticum)
** Abcessen, steenpuisten (zie R./2)
* Acné zie hormonale planten
* Herpes zoster (gordelroos) zie Lavandula e.o.
** Lippenblaasjes kompres, zalf, lipstick
* Mycosis (schimmelinfecties): Inwendig + uitwendig. ook ter voorkoming van recidieven, vaginale candida-mycose
** Psoriasis Zie R./1
* Wonden, vooral geïnfecteerde.
* Insectensteken, slangenbeten traditioneel Indiaans gebruik

Receptuur en bereidingswijzen


Tinctuur gewichtsverhoudingen 1 op 5:
  • Bij acute aandoeningen: 6 x daags 10 druppels
  • Bij chronische klachten of preventief: kuurmatig bvb één week 3 x daags 10 druppels, 1 week stoppen en terug één week gebruiken
Decoct: Verse wortel 10'
Omslagen: 1/3 tinctuur + 2/3 water of hydrolaat van Matricaria of Calendula
Gorgelmiddel: Eventueel + Phytollaca + Calendu­la + Salvia
Zalf: 10 tot 20 %: tinctuur mengen met lanoline of bijenwas
Handelsprodukten: Echinaforce (kuur), VSM Esberitox, vele combinaties met homeopatische middelen Aconitum D12, Belladonna D12 .....

Volgens USP: Powdered Echinacea purpurea Extract is prepared from dried sample solution: Transfer 60 mg of Powdered Echinacea Echinacea purpurea Root, Echinacea purpurea Aerial Parts, purpurea Extract to a round-bottom flask equipped with or a mixture of them, by extraction with hydroalcoholic mixtures or other suitable solvents. The ratio of the start- a condenser. Add 25 mL of Solvent, and heat under reflux,
while shaking by mechanical means for 15 min. ing crude plant material to Powdered Extract is between Centrifuge, or pass through a membrane filter of 0.45- 2:1 and 8:1. It contains NLT 4.0% of total phenols, calcu- µm or finer pore size. lated as the sum of caftaric acid (C13H12O9), chicoric acid Solution A: Phosphoric acid (0.1 in 100) in water (C22H18O12), and chlorogenic acid (C16H18O9), on the dried Solution B: Acetonitrile basis. It contains NLT 0.025% of dodecatetraenoic acid Mobile phase: See Table 1. isobutylamides (C16H25NO), calculated on the dried basis.

Species: R./
Dulcamara Ø 20 ml
Echinacea purp. Ø 30 ml
Geranium robertianum Ø 40 ml         Dos.: 70 dr. 2 x d. uitwendig
Viola tricolor Ø 40 ml                        Ind.: psoriasis

R./
Bellis perrenis Ø 20 ml
Arctium lappa Ø 20 ml
Calendula Ø 40 ml                                     Dos.: 3 x d. 50 druppels
Echinacea angustifolia Ø q.s.p. 125 ml        Ind.: furunkels

Doseringen vlgs Commmission E
  • Internal: 
  • Succus, in 25% solution (95% ethanol): 6–9 ml (Bauer and Liersch, 1993; Commission E; ESCOP, 1999). 
  • Infusion: 1 g in 150 ml water. 
  • Fluidextract 1:1 (g/ml): 1 ml. 
  • Tincture 1:5 (g/ml): 5 ml. 
External:
Ointment: Semi-solid preparation containing at least 15% pressed juice in a base of petroleum jelly or anhydrous lanolin and vegetable oil applied locally.
Poultice: Semi-solid paste or plaster containing at least 15% pressed juice applied locally. 

Over oplosbaarheid van inhoudsstoffen
Cichoric acid is very sensitive to moisture content during storage. Freeze-drying Echinacea purpurea led to a greater retention of cichoric acid than did air drying; the two drying methods preserved caftaric acid equally (Kim et al., 2000). Both cichoric and caftaric acids are phenylpropanoids.  Freeze-drying preserved more alkamides (alkylamides)in Echinacea purpurea roots than did airdrying but the two methods equally preserved alkamide content in its leaves (Kim et al., 2000). The alkamide content in air-dried Echinacea angustifolia roots was higher than in fresh. However, this may be a result of water entrainment during the carbon dioxide extraction rather than an actual change in content during drying. Freeze-drying and air-drying at 50 °C resulted in similar alkamide contents (Sun et al., 2002).

Wetgeving
Het gebruik van alle plantendelen is toegelaten. De voedingssupplementen waaraan de wortel, de wortelstok van Echinacea angustifolia DC. werd toegevoegd, mogen slechts in de handel gebracht worden onder de volgende voorwaarde: het innemen van de in de etikettering of in de reclame aanbevolen dagelijks te gebruiken portie ervan mag niet voor gevolg hebben dat de daardoor ingenomen hoeveelheid hoger is dan de hoeveelheid equivalent met 2,4 g gedroogde wortel

Geschiedenis en Wetenschappelijk Onderzoek
  •  Noord-Amerikaanse Indianen gebruikten vooral de wortels van E. angustifolia tegen slecht genezende wonden, ontstekingen en slangen­beten.
  • Dr. John King, H.W. Derby en C: Eclectic Dispensatory of the U.S. Cincinnati - 1852.
  • Dr. W.H. Felter maakt melding van "... gestoord evenwicht van de lichaamssappen, resul­terend in weefselver­andering... ... stimulerend, reukverdrijvend en anesthetisch ..."
  • Powel (Engeland): "We hebben ontdekt dat Echinacea (in combinatie met Sabal) een grote af­finiteit heeft met de prostaatklier". Health from herbs, Mag. - okt. 1957.
  • Meyer (Duitsland): "Meyer's Blood Purifier".
  • Firma Dr. Madaus & C: Begon met cultuur en onderzoek in Europa. Biol. Schriftenreihe, Heft 13, Radebeul/Dresden - 1939.
  • Stinson: "... ungiftiges Antisepticum, sondern vor allem ein Aphrodisia­cum (lokaal). E. Merck, Darmstadt - 1900.
  • Prof. Wood (Amerikaanse gynecologe): Bij metritis (als er vererging, ettering te verwachten is).
  • R.P. Labadie, A.D. de Lang: Fytofarmaka en Fytotherapie. Uitg. Lab. Biohorma, Elburg. Congres 31 mei 1985.
  • W. Simonsis: Die unbekannte heilpflanze. V. Klostermann.
  • Overzicht Echinacea: Zeitschrift für Phytoth. 9/151-159 - 1988
  • van den Berg: E. purpureae radix ter versterking van de lichaams­eigen afweer bij griepinfecties. Fytotherapie Nieuwsssbrief 17 - sept. 199
Commission E, Duitse officiële commissie ter beoordeling van de kruidenkwaliteit
approved the internal use of E. purpurea herb as supportive therapy for colds and chronic infections of the respiratory tract and lower urinary tract. The Commission E approved external use for poorly healing wounds and chronic ulcerations.

The WHO supports the findings of Commission E regarding internal and external uses of E. purpurea herb. WHO added "treatment of inflammatory skin conditions" to external use (WHO, 1999).

Samenvatting enkele onderzoeken:

Clinical Study: extract of echinacea showed an increase of 50%-120% in immune function over a 5 day period (Jurcic, et al. 1989).
Clinical Study: an extract of echinacea significantly increased the resistance to flu and reduced the symptoms of lymph gland swelling, inflamed nasal passages and headache (Braunig, et al. 1992).
Clinical Study: Of 4500 patients with inflammatory skin conditions, including psoriasis, 85% were cured with topical applications of echinacea salve (Wacker & Hilbig, 1978).
Laboratory Study: Human white blood cells, stimulated by echinacea extract increased phagocytosis (consumption) of yeast cells by 20-40% compared to controls. (Wagner and Proksch 1985)

Enkele referenties
  1. H. Wagner e.a.: Arzneim. Forsch. 35/1069 - 1985.
  2. N. Beuscher e.a.: Acta Agron. Hung. 34 (suppl.)/89 - 1985.
  3. Stoll e.a.: Helv. Chim. Acta 33/1877 - 1950.
  4. G.W. Korting en W. Born: Arzneim. Forsch. 4/424 - 1954.
  5. H. Wagner e.a.: Z. Phytoth. 8/180 - 1987.
  6. J. Bonadeo e.a.: Riv. Ital. Ess. 53/281 - 1971.
Overzicht wetenschappelijk onderzoek: Echinacea AB document M. Godefridi

Links onderzoek

www.nlm.nih.gov/medlineplus/druginfo/natural/patient-echinacea.html
http://www.ema.europa.eu/pdfs/human/hmpc/echinaceae_purpureae_herba/10494506en.pdf
http://www.thorne.com/altmedrev/.fulltext/6/4/411.pdf 

Pharm Biol. 2017 Dec;55(1):649-656.
Studies on phytochemical, antioxidant, anti-inflammatory, hypoglycaemic and antiproliferative activities of Echinacea purpurea and Echinacea angustifolia extracts.
Aarland RC1, Bañuelos-Hernández AE2, Fragoso-Serrano M3, Sierra-Palacios ED4, Díaz de León-Sánchez F2, Pérez-Flores LJ2, Rivera-Cabrera F2, Mendoza-Espinoza JA4.
Echinacea (Asteraceae) is used because of its pharmacological properties. However, there are few studies that integrate phytochemical analyses with pharmacological effects.
OBJECTIVE:
Evaluate the chemical profile and biological activity of hydroalcoholic Echinacea extracts.
MATERIALS AND METHODS:
Density, dry matter, phenols (Folin-Ciocalteu method), flavonoids (AlCl3 method), alkylamides (GC-MS analysis), antioxidant capacity (DPPH and ABTS methods), antiproliferative effect (SRB assay), anti-inflammatory effect (paw oedema assay, 11 days/Wistar rats; 0.4 mL/kg) and hypoglycaemic effect (33 days/Wistar rats; 0.4 mL/kg) were determined in three Echinacea extracts which were labelled as A, B and C (A, roots of Echinacea purpurea L. Moench; B, roots, leaves, flowers and seeds of Echinacea purpurea; C, aerial parts and roots of Echinacea purpurea and roots of Echinacea angustifolia DC).
RESULTS:
Extract C showed higher density (0.97 g/mL), dry matter (0.23 g/mL), phenols (137.5 ± 2.3 mEAG/mL), flavonoids (0.62 ± 0.02 mEQ/mL), and caffeic acid (0.048 mg/L) compared to A and B. A, B presented 11 alkylamides, whereas C presented those 11 and three more. B decreased the oedema (40%) on day 2 similar to indomethacin. A and C showed hypoglycaemic activity similar to glibenclamide. Antiproliferative effect was only detected for C (IC50 270 μg/mL; 8171 μg/mL; 9338 μg/mL in HeLa, MCF-7, HCT-15, respectively).
DISCUSSION AND CONCLUSION:
The difference in the chemical and pharmacological properties among extracts highlights the need to consider strategies and policies for standardization of commercial herbal extracts in order to guarantee the safety and identity of this type of products.





Complementary and alternative medicine (CAM) use by patients enrolled in phase I clinical trials.


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Arthrobacter sp. EpRS66 and Arthrobacter sp. EpRS71: Draft Genome Sequences from Two Bacteria Isolated from Echinacea purpurea Rhizospheric Soil.
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Onderzoek: Echinacea veilig tijdens zwangerschap

Verkoudheid, voorhoofdsholte-ontsteking en bronchitis komen vaak voor en fytotherapeutica op basis van echinacea worden veelvuldig toegepast bij klachten van deze aard. Ook onder zwangere vrouwen zijn echinaceaproducten zeer populair. Er is echter nog slechts weinig bekend over de veiligheid van echinacea voor het ongeboren kind.

Momenteel is er slechts één prospectieve, observationele studie met betrekking tot dit onderwerp beschikbaar. In deze studie werden 206 vrouwen gevolgd die tijdens de zwangerschap echinace-aproducten hadden geslikt. Van deze vrouwen had 54% alleen in het eerste trimester echinacea gebruikt en 8 % gedurende de gehele zwangerschap. Bereidingen in cap­sule en/of tabletvorm werden gebruikt door 58% en tincturen door 38% van de respondenten. De dosering varieerde bij de capsules en tabletten van 250 tot 1000 mg per dag. De verschillende producten bevatten voor­namelijk de twee echinacea-soorten E. angustifolia DC. en E. purpurea (L.) Moench waarbij echter geen melding werd gemaakt van het gebruikte plantendeel. Slechts één van de vrouwen had een product met E. pallida (Nutt.) gebruikt.

Het overgrote deel van de vrouwen vertelde baat te hebben gehad bij de door hen gebruikte produc­ten (81%) en schatte zelf het risico hiervan als laag in (95%). In de studiegroep traden 13 spontane abortussen op en werd één zwangerschap op medische gronden afgebroken. In totaal werd aan 195 babies het leven geschonken, waarvan drie tweelingen. Zes ernstige aan­geboren afwijkingen werden gevonden, waaronder één van chromosomale aard. In vier van de zes gevallen werd de aangeboren afwijking geconstateerd bij vrouwen die in het eerste trimester van de zwangerschap echinacea hadden gebruikt. De studiegroep bleek echter voor geen enkele van de onderzochte parameters af te wijken van een speciaal geselecteerde, vergelijkbare controlepopula­tie.

De auteurs concludeerden dan ook dat gebruik van echinacea tijdens de zwangerschap, in de periode dat de organen worden gevormd, niet lijkt te kunnen worden geassocieerd met een detecteerbare toename van de kans op aangeboren afwijkingen.

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. Arch Intern Med 2000;160:3141-3.



Echinacea-preparaat onderzocht.

Enkele onderzoekers van de Cardiff School of Biosciences (Verenigd Koninkrijk) hebben een gerandomiseerde gecontroleerde studie uitgevoerd met een gestandaardiseerd Echinacea purpurea preparaat (oertinctuur van 95% herba en 5% radix), dat werd gegeven aan 755 gezonde vrijwilligers gedurende vier maanden (profylactisch 2,4 g/dag en tijdens verkoudheden 4 g/dag). Uiteindelijk konden 673 personen geanalyseerd worden. In de verum-groep kwamen 26% (significant) minder verkoudheidsdagen voor dan in de placebogroep: 672 dagen/149 infecties versus 850 dagen/188 infecties. Bijwerkingen waren op het niveau van de placebo. De betrokken virussen werden geïsoleerd en gedetermineerd.  

Bron: Jawad M, Schoop R, Suter A, Klein P, Eccles R. 2012. Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double-blind, placebo-controlled trial. Evid Based Complement Alternat Med doi:10.1155/2012/841315.



Myths About Echinacea

Misinterpretation of the scientific literature regarding Echinacea's effect on the immune system has led to the development of several myths regarding Echinacea's therapeutic use including: (1) Echinacea is only appropriate for short-term use because it is not desirable to stimulate the immune system continuously, [ 4 ] and (2) Echinacea is an immune stimulator and as such, its use may be contraindicated in "progressive conditions" such as tuberculosis, leukemia, allergies, collagen disorders, multiple sclerosis, HIV/AIDS, and autoimmune disease. [ 5 ] However, the Native Americans' and Eclectics' high-quality, traditional-use data is a result of decades of extensive clinical experience, and does not support the suggested limitations. King [ 2 ] and Ellingwood6 recommended long-term use of Echinacea for a variety of chronic conditions, including tuberculosis and autoimmune-related disorders. Similarly, neither modern research data nor authoritative herbal reference sources support the suggested limitations on Echinacea use. Numerous clinical studies of Echinacea have been conducted over the last 20-30 years that overwhelmingly demonstrate its therapeutic benefit and safety, even in patients with autoimmune disorders. [ 7,8 ] The British Herbal Pharmacopoeia, [ 9 ] The British Herbal Compendium, [ 10 ] and The Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics [ 11 ] list no contraindications for Echinacea. Weiss also suggests Echinacea has an excellent safety profile and no side effects. [ 12 ]
http://www.thorne.com/altmedrev/.fulltext/6/4/411.pdf 



Cultivation Practices of Echinacea species

E. purpurea can be grown almost anywhere within the temperate zones and is being cultivated in most of these areas. It prefers a well-drained alkaline soil in a sunny location.
Recommendations for pH range from 6.0 to 7.0. E. purpurea will tolerate light or dappled shade and can withstand hot and dry conditions. Raised beds are highly recommended, especially for moist or clay soils. Poorly drained soils should be avoided.
Planting
Propagation can be from seed, transplants, or divisions. Divisions can be done from the crowns of mature plants when the plants are dormant, in early spring or in fall. Cut the roots into several pieces making sure buds and fibrous roots are included in each division.
Transplant immediately into well prepared, permanent, planting beds. Space divisions twelve to eighteen inches apart, making rows eighteen to thirty-six inches apart. Weed control is very important, as echinacea does not compete well with weeds. Plants will benefit from the use of straw or shredded bark mulch.
Johnny’s Selected Seed Co., Winslow, Maine, recommends the following guidelines for starting seeds indoors. Echinacea requires light for seed germination. Using deep containers to allow for good root development, fill with a prepared soil mix, and plant seeds in flats or pots, pressing lightly into the soil and barely covering the seed with a sprinkling of soil.
Moisten, cover, and refrigerate at 40-500F. Johnny’s has found that E. purpurea does not need pre-chilling to germinate, but germination will be enhanced if exposed to the cold temperatures for seven days. After chilling, move flats or pots to warmer temperatures (680-770F) to allow for emergence of the seedlings. Germination generally occurs ten to twenty days after seeds are exposed to warm temperatures. When plants are several inches tall (usually eight to twelve weeks after germination), transplant seedlings outdoors in late spring or early summer. Apply mulch to control weeds.
Seeds can be sown directly in the ground in fall or early spring, but a fine seedbed needs to be prepared. Plant seeds just under the soil surface spacing them two inches apart. Keep the bed moist and weed-free. When seedlings emerge, thin plants to the recommended spacing mentioned above.
Insects and Diseases
Diseases that affect echinacea include the leaf spots Cercospora rudbeckii and Septoria lepachydis and can cause blackening of the leaves. A root rot, Phymatotrichum omnivorum, has also been identified. Another disease called “aster yellows disease” is a virus that is transmitted by a leafhopper feeding on echinacea. Other insects that feed on echinacea include Japanese beetles and thrips. Practicing four to five year crop rotations, planting in well-drained soil, and preventing over watering can prevent most disease problems.

Harvesting, Cleaning, and Drying
Echinacea root is harvested in the fall after the plant has gone dormant, usually the second to fourth growing season, depending on which planting method is used. A spading fork or other hand digging tools can be used as well as a mechanized harvester, such as a modified potato digger. Shake the roots free of dirt and carefully remove roots that are not echinacea. It is not acceptable to include foreign material, whether weeds or rock, in with the Echinacea root. (Even echinacea stems are consider foreign material if you are selling the roots.) Put plants in the shade until harvesting is complete. When ready for processing, it is recommended to wash echinacea roots with a pressure hose. Richo Cech, author of Growing At-Risk Medicinal Herbs, recommends cutting the crowns to remove dirt and small stones that get lodged at the base of the crowns. Cech recommends processing the echinacea as soon as possible after washing to minimize oxidation.
Once the roots are cleaned, spread on non-aluminum screens for the drying process. The roots need a warm location with adequate airflow. If a drying unit is not available, a large dehydrator, converted greenhouse, or converted rooms in a barn are areas that can be used for drying. According to Cech, “Dry for one day at 700F, then turn the temperature up to 1100F, drying the roots until they snap.” Cech recommends “storing the dried root in plastic bags in light-proof sacks or drums, in a cool, dark, and dry location for up to one year.”
Reports of estimated yields of the dried root ranged from 1000 to 2500 pounds per acre after
three growing seasons.
Currently, there is a limited market for the aerial parts (above ground) of E. purpurea.
Great care must be taken to minimize the amount of soil that can splash up onto the leaves and stems during wet weather. (This crop will not be saleable if sand or dirt is embedded in the leaves.) With sufficient growth, the leaf can be harvested the first growing season and subsequent years to follow. In areas like the piedmont of North Carolina, two cuttings of the aerial parts are possible the first year if transplants are put into the field in May. Higher temperatures for drying aerial parts are required for E. purpurea if grown in high humidity regions. In the final growing season, the root can be harvested in the fall.




Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double blind, placebo-controlled trial. Evid Based Complement Alternat Med. 2012:841315. Sep 16.
Colds and flu, associated with a variety of viral infections, are characterized by symptoms such as sore throat, cough, and nose irritations, as well as systemic complaints such as headache, malaise, and fever. The common cold alone causes great discomfort and is a major reason for school and work absences, as well as physicians visits.1 Preventative strategies have included antiviral agents or vaccines targeted towards infection prevention or inhibition of viral replication; however, common problems arise with adverse side effects (ASE) and/or the failure to protect certain populations.
Echinacea (Echinacea purpurea, Asteraceae) is used widely as an immune system modulator as well as in common cold prevention strategies.2 Many clinical studies investigating the use of echinacea in cold prevention have shown conflicting results or have had too small a sample size to detect significant effects. However, significant preventive effects were observed when 3 trials on standardized echinacea extracts were combined in a meta-analysis.3 (These studies were conducted by Bioforce AG in cooperation with Sebastian Johnston, MD, PhD, from the Imperial College in London.) Finally, tolerability and safety are critical considerations for therapies designed for long-term, preventive use. The most recent randomized, double-blind, placebo-controlled trial investigated the safety profile and efficacy of the long-term usage of a proprietary echinacea formulation for prevention of colds and flu.

This study took place at the Common Cold Center at Cardiff University in Cardiff, Wales. Healthy subjects were randomized to either echinacea or placebo for 4 months. At the initial clinical visit, subjects received study medication for 1 month in addition to a diary for documenting ASEs, incidences of colds and associated symptoms, and medication use other than given treatments. Subjects brought unused treatments and completed diaries to monthly clinical visits and also were given kits to take nasal swabs for viral identification.
An alcoholic extract of fresh echinacea extract was used in this trial (Echinaforce®, made from E. purpurea, 95% aerial parts and 5% roots, prepared by Bioforce AG; Roggwil, Switzerland). Material was standardized to 5 mg/100 g of dodecatetraenoic acid isobutylamide and tested negative for endotoxin. Placebo was comparable in appearance, smell, and taste, with the same percentage of alcohol and identical packaging. Total dosage was based on Bioforce AG’s instructions and consisted of 0.9 ml of extract or placebo 3 times per day in water; this material was held in the mouth for 10 seconds (2,400 mg of extract daily) in order to achieve maximal local antiviral and anti-inflammatory effects at the pharynx. If subjects had a cold, they were asked to increase dosage to 0.9 ml 5 times per day (4,000 mg of extract). Leftover bottles were weighed for remnant of extract, and diaries were consulted to assess compliance. 
Subjects were recruited on campus, at least 18 years old, and in good health with a recent history of 2 or more colds per year. Those pregnant, who had a chance of becoming pregnant, who were breastfeeding, who had a cold at the time of recruitment, who were on either antiviral or antibacterial medication, who abused drugs or alcohol, or who suffered from psychological diseases or epilepsy were excluded. Exclusion criteria also did not permit subjects with the following: a history of suicide attempts, upcoming surgery, chronic or autoimmune diseases, and asthma or allergies, particularly to members of the Asteraceae plant family. A preliminary study showed blinding to be efficient as approximately half the subjects in both the echinacea and placebo groups guessed that they had the echinacea treatment. Additionally, a power calculation based on a beneficial effect of 25% with the echinacea treatment and a protocol deviation and drop-out rate of 20% yielded an ideal sample size of 750 participants for the efficacy variable (number of days with colds).  
Blood samples were taken from subjects for screening of blood cell counts and hematological and other measurements. Both subjects and physicians were asked to rate echinacea tolerability. Descriptions for ASEs as related to the treatments ranged from “not related” to “certain.” Those ASEs that were “possibly” associated with treatment were considered adverse drug reactions (ADRs). Parameters for colds included the amount of colds, the total number of days with colds, and colds that required addition medication. Characterization of viral infections was also conducted.

Out of 755 subjects included and randomized, 82 subjects dropped out, leaving 673 who finished the study regularly. Reasons for subject dropout included loss of contact (there was no contact post randomization; n=38), withdrawal of consent (n=16), “technical reasons” (n=3), health or ASE problems (n=3), and unknown reasons (n=22). There were no baseline differences between groups with the exception of cold susceptibility; subjects randomized to the echinacea group were, by chance, significantly more susceptible to colds than those in the placebo group (P<0.05). This was expected to bias the efficacy results against the echinacea group.
ADRs were reported by 9.0% of the echinacea group and 10.0% of the placebo group; the echinacea treatment was identified to be non-inferior to placebo treatment in regard to the rate of occurrence, as even fewer ADRs were observed. In the echinacea group, 177 subjects documented 293 ASEs, and 172 subjects in the placebo group mentioned 306 ASEs. Also, in the echinacea group, 4 ASEs resulted in discontinuation of treatment, while 3 ASEs caused discontinuation in the placebo group. One severe ASE was reported in the placebo group while none were reported from the echinacea group. No significant differences were detected in the amount of ASEs between groups. Also, no significant differences were reported in the blood parameters either after echinacea treatment or between groups. Assessment of tolerability by subjects resulted in ratings of “good” or “very good” in 64% of the echinacea group and 71% of the placebo group.
Those in the echinacea group experienced 149 colds lasting a combined total of 672 days, while subjects in the placebo group reported 188 colds with a length of 850 days. The total number of days with colds was significantly fewer in the echinacea group than the placebo group (P<0.05, as measured in the intention-to-treat population). Those in the echinacea group also experienced fewer recurring colds than those in the placebo group (65 vs. 100, respectively; P<0.05). In addition, a greater number of subjects with colds in the placebo group used medication such as aspirin, paracetamol (acetaminophen), and ibuprofen as compared with those in the echinacea group (88 vs. 58, respectively; P<0.05).
Of the nasal swabs collected (n=201), viral infection was identified in 54 samples from the echinacea group and 74 in the placebo group. Significantly fewer samples from the echinacea group contained influenza, corona-, metapneumo-, respiratory syncytial-, and parainfluenza viruses as compared the placebo group (24 vs. 47, respectively; P<0.05). Additionally, in subjects with 100% protocol compliance, 36 colds with a combined total duration of 155 days were reported from the echinacea group (n=88) as compared with 58 colds in 268 days in the placebo group (n=99, P<0.0001).

In summary, preventive therapies for colds and flu should be both well tolerated and efficacious. The echinacea preparation used here exhibited a very “good” safety profile for long-term usage. This study reports that echinacea long-term prevention was associated with fewer cold episodes, fewer days with colds, and fewer colds that required additional medication, suggesting efficacy against infection. The study mentions that these data may have been confounded by the significant difference of cold susceptibly between groups and less use of pain-relieving pharmaceutical drugs in the echinacea group. If an adjustment for these co-variables had been conducted, an even more beneficial preventive effect for the echinacea formulation probably would have been shown.   
This study also characterized viruses. Although the sample size was small, those in the echinacea group had significantly fewer viral infections than those in the placebo group. This may preliminarily indicate clinical antiviral activity as it agrees with the authors’ in vitro results on the same proprietary extract (Echinaforce). In conclusion, this study claims to be not only the largest ever conducted on the clinical effects of echinacea, but the first to employ the detection of specific viruses in this manner. The conclusions from this well-powered, robust clinical trial contribute substantially to the case for the use of echinacea preparations, particularly this specific formulation, in common cold prevention.
 
—Amy C. Keller, PhD
 
References
1. National Institute of Allergy and Infectious Diseases: common cold overview. August 17, 2012. Available at www.niaid.nih.gov/topics/commonCold/Pages/overview.aspx. Accessed September 9, 2012.
2. Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: American Botanical Council; Newton, MA: Integrative Medicine Communications; 2000.
3. Schoop R, Klein P, Suter A, Johnston SL. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis. Clin Ther. February 2006;28(2):174-183.



Geschiedenis van Echinacea sp. in USA

Original Eclectic Preparations and Official Recognition
Dr. H.F.C. Meyer of Nebraska was the first to produce a commercial extract of echinacea. Although usually combined with about one-eighth part each of hops (Humulus lupulus, Cannabaceae) and wormwood (Artemisia spp., Asteraceae) — plant parts not specified — in his Meyer’s Blood Purifier for internal use, he used the tincture of E. angustifolia root for local applications (either externally or internally to mucosa in the nose, mouth, and rectum).1,2 In 1887, Meyer and Dr. John King2 described Meyer’s use of the root for 16 years as an “alterative”† and antiseptic in the Eclectic Medical Journal, claiming that the tincture was effective internally and externally for treatment of boils, carbuncles, ulcers of the throat and extremities, hemorrhoids, and wasp and bee stings. In 613 cases of rattlesnake venom poisoning treated in humans and animals, most recoveries occurred in two to 12 hours.
By 1900, most Eclectic physicians were using Lloyd Brothers Pharmacists’ E. angustifolia extracts, following years of study by J.U. Lloyd.1 After privately supplying a tincture of E. angustifolia root to Eclectic investigators beginning in 1890, in 1894 the Lloyd brothers introduced their commercial Specific Medicine Echinacea to the medical profession.3,4 J.U. Lloyd determined that the characteristic acrid principles of the dried root that produced a tingling and numbness of the tongue required a high-alcohol concentration for extraction.1 By 1906, the use of echinacea as an external and internal remedy had extended to conventionally trained physicians. It also was being used by them for the treatment of infected wounds, septicemia, and poisonous insect bites and stings.5

The Lloyd Brothers Pharmacists manufactured various E. angustifolia preparations. Their Specific Medicine Echinacea with 65% alcohol (ethanol) had the same drug strength as a fluid extract (1:1), but its production involved a proprietary process.6 Other Lloyd brothers preparations included Echafolta, a refined preparation free of sugars and coloring matter and made with 92% alcohol. Considered equivalent to Specific Medicine Echinacea, Echafolta was the preferred choice in surgical cases, where greater cleanliness was desired.1,6 By 1922, a small quantity of iodine tincture had been added to Echafolta, causing it to be reserved for external use only.7 Echafolta Cream provided the active principles in a bland petrolatum base.8 It was used locally as a soothing dressing and as an adjunct to internal medication and surgical measures.1,6 A nonalcoholic extract of E. angustifolia for hypodermic use was given the trade name Subculoyd Echinacea.4 While occasionally specifying the specific type of preparation, most physician reports of E. angustifolia root extracts refer to whatever preparation was used simply as “echinacea.”
The Lloyd brothers emphasized the quality of their product as follows:
Echinacea is made from the carefully selected, prime, dried, cured, and assayed root of E. angustifolia. The quality of but few drugs is more influenced by conditions prevailing in different localities and by treatment during drying, than is Echinacea…. Prime drug from favored geographic regions may be ruined by careless or faulty manipulation…. The famous Lloyd process permits the extraction of delicate and complex botanical therapeutic principles without harm.8
The Lloyd brothers’ ongoing laboratory research led to their 1923 statement that “the therapeutic importance of the acrid constituent emphasized in our former literature constitutes but a part of its qualities, being most pronouncedly supported by less sensible constituents.”3
American Medical Association Condemnation Despite Acceptance by Physicians and the National Formulary
In 1909, a report by the Council on Pharmacy and Chemistry in the Journal of the American Medical Association condemned Dr. Meyer’s “absurd” claims and those “made on no better basis than that of clinical trials by unknown men who have not otherwise achieved any general reputation as acute, discriminating and reliable observers.”9 The report declared that “Echinacea is deemed unworthy of further consideration until more reliable evidence is presented in its favor.”9

Dr. Finley Ellingwood, the Eclectic materia medica professor at Bennett Medical College in Chicago, Illinois, responded to the Council on Pharmacy and Chemistry with the following:
Not a single member was engaged in active medical practice or was in a position to observe the action of drugs in the influence they exercise in the cure of disease…. In view of the fact that 20,000 physicians of the United States are using this remedy with success; and in view of the fact that there is a perfect agreement concerning the observations made by these reliable and trustworthy practitioners, … it seems strange indeed that this half dozen or more men should say that because of the scrutiny (or lack of scrutiny) that had been made, the remedy is deemed unworthy of further consideration.10
Clinicians remained enthusiastic about the usefulness and efficacy of echinacea after the condemnation published in the Journal of the American Medical Association. A survey was sent by the Lloyd brothers to more than 30,000 physicians who graduated from an array of medical schools, asking them to indicate which botanical drugs they used in their practices. More than 10,000 responded, and Echinacea ranked eleventh (listed by 5,065 physicians) in importance among all botanical drugs, as published in 1912 in the Journal of the American Pharmaceutical Association.11
In 1916, the fourth edition of the National Formulary,12 published by the United States Pharmacopeia, established E. angustifolia dried roots and its fluid extract as official remedies. In testing the manufacture of a standard echinacea fluid extract in 1911 for inclusion in the National Formulary, it was concluded that menstruums with less than 67% ethanol did not adequately extract from the dried root those pungent principles responsible for the tingling sensation in the mouth (now known as alkamides).13

Early Scientific Assessments of E. angustifolia Root Extracts
The first major clinical research performed with E. angustifolia was conducted from 1913 to 1916 by Dr. V. von Unruh, a United States Army lieutenant. He used the nonalcoholic injectable medications Subculoyd Echinacea and Inula Compound (1.0 and 1.33 mL, respectively, intramuscularly or intravenously; Inula Compound also contained an extract of the root of elecampane [Inula helenium, Asteraceae]) in the treatment of patients with tuberculosis. Among 150 patients, he described 100% recovery in those with incipient pulmonary disease, 50% arrest in those with moderately advanced disease, but no success in those with advanced disease.14,15 In microscopic research involving more than 500 differential and cell counts carried out over more than four years, he found that injected Echinacea extract raised the opsonic index (making bacteria more susceptible to phagocytosis), increased the phagocytic power of leucocytes (allowing white blood cells to more readily engulf bacteria), improved leukopenia and hyperleukocytosis (helping normalize insufficient and excessive numbers of white blood cells), and normalized the percentage of mature neutrophils (balancing the number of the primary phagocytes for infections).15
Couch and Giltner subsequently tested the major echinacea products in animals.16 Performing injections in relatively small numbers of guinea pigs, they used bacterial toxins to experimentally induce tetanus and botulism, rattlesnake venom to simulate snakebites, and live bacteria to cause tuberculosis, dourine (a type of chronic venereal disease in animals), anthrax, and septicemia. Control animals were untreated or were administered the same alcohol content as in the extracts. Echinacea prepar-ations (Specific Medicine Echinacea, Subculoyd Inula and Echinacea, or Echinacea fluid extract [National Formulary, 4th ed.]) were administered orally or parenterally before and/or after the pathologic injections. The induced diseases were interpreted as essentially the same in the control and treated animals. The authors concluded that the echinacea preparations were not of value in the treatment of diseases produced by microorganisms or biologic toxins.17,18
A 1921 editorial review of these findings published in the Journal of the American Medical Association noted:
“Of course, it will be retorted that the negative results on laboratory animals need not necessarily apply to sick human beings, and that subtle potent effects are not always discovered by research workers… Scientific medicine of today, however, asks for evidence that can be demonstrated by the pharmacologist or can be appreciated and accepted by the critical clinician as well as the quack.”16
The authors argued that the Echinacea fluid extract used in the experiment should be removed from the National Formulary.16
The same year, James Beal19 — director of pharmaceutical research at the University of Illinois, Urbana, and former editor of the Journal of the American Pharmaceutical Association — published a critical response to the laboratory research. He noted that the experiments were too few to be conclusive and that the results were not interpreted from a clinical perspective. Three times the minimum fatal dose of tetanus was administered to 19 animals receiving Specific Medicine Echinacea; 10 times the minimum fatal dose of botulinus was administered. The septicemia and dourine produced by Bacillus bovisepticus and Trypanosoma equiperdum, respectively, were species that were unassociated with human pathologic conditions. He further noted that, in the tuberculosis experiments, the mean weight loss in control animals was 129% that of the treated animals, which survived 36% longer. Of the animals injected with rattlesnake venom, the three controls died, while one of the six echinacea-treated guinea pigs survived.19

Responses of Clinical Empiricists
The Lloyd brothers, as a courtesy to Couch and Giltner and in fairness to all concerned, publicized their experimental results and suspended advertisements of echinacea preparations for one year, despite the fact that echinacea products were their best-selling botanicals from 1885 to 1921.17,18 Following publication of the 1921 negative laboratory research, the Lloyd brothers recorded their best sales of echinacea extracts by even larger margins over other botanicals. In 1922, echinacea sales increased again, almost 25 percent above the previous year’s sales and more than three times more than sales of the second-ranked plant drug, fringe tree (Chionanthus virginicus, Oleaceae), among their 239 different plant remedies.3
In another attempt to assess the value of echinacea, the Lloyd brothers sent a postcard questionnaire to physicians concerning the use of echinacea preparations in their clinical practice in 1921. They asked for the physicians’ prominent indications and uses of echinacea, providing one line for the response and two additional lines for remarks. Physicians were asked to consider whether they would be willing to use a synthetic or other substitute to replace echinacea. In 1923, the responses were published.3 This unparalleled document provides ardent empirical consensus to support prior clinical claims.
In comments received from 701 physicians who used E. angustifolia preparations in their practices, 70.3% (493 respondents) advocated its general use in septic conditions, 22.1% (155 respondents) specified its effectiveness in cases of septicemia or blood poisoning, and 14.3% (100 respondents) noted its efficacy for treatment of typhoid fever (Table 1). Use in cases of blood “dyscrasias” — a morbid imbalance of component elements; as used by Eclectics (see footnote ‘d’ in Table 1), this is considered descriptive of blood disorders, blood perversions, blood trouble, blood diseases, vitiated blood, morbid blood, etc. — by 21.4% (150 respondents), and as an alterative by 11.3% (79 respondents) were cited as other major indications. J.U. Lloyd3 noted that neither tetanus nor botulism was mentioned in any of the survey responses, nor had treatment with echinacea been recommended for these conditions in major Eclectic texts, challenging the pertinence of the findings by Couch and Giltner.17,18 However, a striking feature of the survey results was that most indications mentioned by physicians for E. angustifolia root preparations were for bacterial infections while few mentioned viral or fungal infections.3

Medical Use of E. angustifolia Root Extracts for Respiratory Infections
Notably, when E. angustifolia was first introduced to clinical medicine in the late 19th century, scant mention was made of its use in treating simple upper respiratory tract infections. In 1898, Felter and Lloyd1 noted that E. angustifolia hydroalcoholic extract contributed much to the cure of catarrh of the nose, nasopharynx, and respiratory tract. In a 1919 summary by the Lloyd brothers21 of reports from 1,000 physicians asked to cite the most important flu remedy following the recent influenza pandemic, echinacea was not listed among the nine most useful remedies for influenza or pneumonia, or among the nine best external applications for either of these conditions. Echinacea was noted in passing by some physicians who listed it when certain remedies were most indicated, for example, “where sepsis is marked, Echafolta or Echinacea becomes most important.”21
That same year (1919), when E. angustifolia extracts were recommended by Ellingwood22 for catarrhal conditions, it was cited both as an internal and as a local medication. In the survey responses from 701 physicians published by J.U. Lloyd3 in 1923, 10 respondents mentioned influenza as a prominent indication for use of echinacea, while only two specified its use for catarrh and one specified it for colds.
The use of echinacea extracts for treating influenza was discussed in 1929 by H.T. Cox,23 who believed (as is the general consensus today) that early application of “good-sized doses” from the first day until the body temperature reached normal was the best means of using this remedy. However, even after several days of influenza, echinacea in “large enough dosage” still was used persistently. In patients with purulent expectoration, the dosing continued until the sputum cleared. Echinacea angustifolia was prescribed along with appropriate cough preparations until the pulmonary congestion was entirely resolved. Large doses (the author again referred to “good-sized doses”) were administered to patients with influenza until the cough subsided.

Eclectic Human Research and Decline
Preliminary human research was attempted in 1934, when students at the Eclectic Medical College in Cincinnati, Ohio, volunteered as subjects to study the effects of echinacea by taking therapeutic doses for four days. Specific Medicine Echinacea was administered in water in doses of two-to-15 minims, derived from two-to-15 grains (130-975 mg) of the dried root. Blood samples were drawn at baseline and again after each day of use. Increases in total leukocyte counts were apparent, peaking in two-thirds of the subjects after 24 hours and in the remaining one-third after 48 hours.24 The leukocyte increase was mostly neutrophils after 24 hours and mostly lymphocytes after 48 hours. Total and differential counts were normal after 72 hours. These uncontrolled results, crude by modern standards, suggest that echinacea combats infectious agents acutely, briefly, and indirectly through the blood.
Echinacea angustifolia use diminished after the decline of Eclectic medicine in the late 1930s. This was indicated by the dropping of Echinacea fluid extract from the eighth edition of the National Formulary25 in 1946, although the dried roots entry appeared in this official text that year for the last time. In 1950, in an attempt to identify direct antibacterial activity, German researchers isolated the caffeic acid derivative echinacoside from the root, which demonstrated weak inhibition of streptococcal and Staphylococcus aureus gram-positive bacteria.26

Adoption by Naturopathic Physicians
Echinacea angustifolia was prescribed by early naturopathic physicians for local and internal use in accord with the indications established by the Eclectics. Echinacea was considered one of naturopathy’s most valuable herbs. In 1936, Specific Medicine Echinacea was recommended by naturopathic physicians as an alterative for septic conditions.27 In such cases, 20 drops of Specific Medicine Echinacea in a little water every four hours was suggested for treatment of recurring boils, carbuncles, ulcerations, and lymphangitis (inflamed lymphatic vessels). Septic fevers, typhoid fever, and acute nephritis were treated with 20 drops every two hours until the crisis passed. This preparation was to be administered internally and applied locally as a wet dressing for snakebites, cuts, wounds, and insect stings.
Twenty years later, the Echinacea fluid extract was advocated again in a naturopathic journal as a treatment for septicemia, as an antiseptic for boils, and as a local application for swelling.28 A tincture of the fresh root (one teaspoonful every two-to-four hours) was recommended in patients with diphtheria and puerpural septicemia. It was often combined with other appropriate remedies.28,29
In 1953, the Naturae Medicina and Naturopathic Dispensatory recommended hydroalcoholic extracts of the dried root of E. angustifolia, along with its water-based decoction, as “one of Naturopathy’s most faithful antibiotics and alteratives.”29 Internal use of the tincture or Specific Medicine Echinacea, together with its external application, was emphasized again for insect stings, boils, carbuncles, and certain septicemias. The tincture or decoction was used as a gargle for buccal ulcerations, ulcerative stomatitis, gingivitis, tonsillitis, pharyngitis, and as a retention colonic for ulcerative colitis. In a mixture with glycerin, it was applied on a tampon for eroded cervix and nonspecific vaginitis with leucorrhea.29
Notable natural medicines excluded from this compendium29 were opiates and antibiotics. The absence of antibiotics is particularly noteworthy because their use had been addressed positively by John Bastyr, the renowned naturopathic physician, in an article in the Journal of the American Naturopathic Association in 1950.30 He discussed in detail the use of penicillin, streptomycin, aureomycin, bacitracin, polymyxin, neomycin, terramycin, and others. These products were considered by Dr. Bastyr to be appropriate for use on a selective basis, being derived from lower plant life forms according to the taxonomic classifications of that time.
Naturopathic physicians treated many infectious diseases without modern antibiotic medicines. This was primarily due to the disruptive effects that these powerful medicines had on symbiotic bacteria in the intestines. Natural methods of destroying germs and stimulating natural immunity were used preferentially.31 Dr. Bastyr30 specifically noted the antibacterial efficacy of allicin from garlic (Allium sativum, Liliaceae) and extracts of sagebrush (Artemisia tridentata, Asteraceae), juniper (Juniperus communis, Cupressaceae), and buttercups (Ranunculus spp., Ranunculaceae), when prescription antibiotics were inappropriate or if a change of therapy was required.
Dr. Bastyr also used E. angustifolia root tincture internally for the treatment of septicemia, pyuria (pus in the urine), and gangrene.32 He administered it to treat coughs and colds, and to boost deficient immune function in many infections. For the treatment of infections, echinacea was used frequently in combination with other immune-enhancing and antimicrobial botanicals. A fundamental formula used by Dr. Bastyr combined four parts E. angustifolia root extract, four parts goldenseal (Hydrastis canadensis, Ranunculaceae) rhizome extract, and one part poke (Phytolacca americana, Phytolaccaceae) root extract. He also spoke highly of adding wild indigo (Baptisia tinctoria, Fabaceae) root to this formula. He often would combine five parts echinacea with one part wild indigo for infections, and administer 60 drops three times daily. He used diluted echinacea extract topically to treat decubitus ulcers as well.

A modern E. angustifolia fresh root (1:1) 65% ethanol extract (Specific Echinacea Extract, Eclectic Institute, Inc.; Sandy, Oregon [manufactured using the Lloyd extractor]) administered orally to six male rats in their drinking water for six weeks recently was shown to increase the initial antigen-specific day 0 induction of immunoglobulin G (IgG) antibody response after seven days and subsequent day 10 antigen inductions of IgG on days 14, 21, 24, and 27, in a statistically significant manner compared with four control rats (range, P=0.04 to P=0.002).33 Non-significant IgG increases also occurred on days 10, 18, and 32, but not after the third antigen challenge on day 35. Although increases in antigen-specific immunoglobulin M occurred on all of the aforementioned days, as well as on days 35 and 39, none of these increases were significant compared with control animals. These results suggest that this fresh root extract may enhance subacute immune responses by increasing antigen-specific antibody production.

Introduction of Echinacea purpurea
Other Echinacea species (e.g., E. pallida root in the fourth [1916] and eighth [1946] editions of the National Formulary12,25) sometimes were used as substitutes for E. angus-tifolia.28 Echinacea purpurea was mentioned by Dr. John King in his Eclectic American Dispensatory (1853) as a remedy deserving “a full and thorough investigation from the profession;”1 at that time, E. purpurea also was known by the synonym Rudbeckia purpurea and occasionally was confused with E. angustifolia, although rarely used by the Eclectics.1
Echinacea angustifolia had been introduced into homeopathic practice in Europe in the late 19th century. Because of a severe shortage of this drug in Europe in the 1930s, the German phytopharmaceutical manufacturer Gerhard Madaus went to the United States to obtain seeds of E. angustifolia; however, he mistakenly bought E. purpurea seeds.34,35 Consequently, Madaus decided to extract the juice from the aboveground (aerial) part of the blooming E. purpurea plant.35 Preserved with 22% alcohol, E. purpurea plant juice with cichoric acid and water-soluble arabinoxylan and arabinogalactan polysaccharides is distinct from E. angustifolia root extracts in greater than 50% ethanol with echinacoside and is distinguishable from lipophilic alkamides.36 Because E. purpurea juice previously had not been used clinically, Madaus experimented with its use. Since then, much European research on Echinacea has used this preparation (Echinacin®, Madaus AG; Koln, Germany ) or similar preparations internally and externally.34-36
In the 1950s, the Swiss naturopath Alfred Vogel37 traveled to America and learned the native uses of E. angustifolia from Native Americans of the Lakota (Sioux) tribe in South Dakota. Finding that the related species E. purpurea was effective and easier to harvest, he returned with seeds of this species to cultivate in the Swiss “lowlands” at 4,500 feet above sea level (ca. 1,600 m). After 10 years, when these plants had acclimated sufficiently to produce flowers, he began using the tincture of the whole fresh plant to strengthen the immune response to infectious conditions. Vogel’s E. purpurea extract combines 95% aerial plant with 5% roots in 65% ethanol (Echinaforce®, Bioforce AG; Roggwil, Switzerland).
In 1989, the German Commission E officially approved the fresh-flowering E. purpurea aboveground plant and its preparations for “supportive treatment” of colds and chronic infections of the respiratory and lower urinary tracts, and, externally, for poor wound healing. In 1992, E. pallida fresh or dried root was recognized officially by the Commission E as supportive therapy in influenza-like infections, particularly the 50% alcoholic tincture. However, the roots of E. purpurea and E. angustifolia were not approved, due to lack of adequate clinical data available at the time.38 Echinacea purpurea, E. angustifolia, and E. pallida roots are phytochemically distinctive (Table 2).36 Surprisingly, although water extracts of E. purpurea roots were potent against influenza virus, and although ethanolic fractions and alkamides of E. angustifolia root inhibited rhinovirus in vitro, the E. pallida root water and ethanolic fractions were ineffective against both.39 European experience and clinical research with the cultivated E. purpurea plant led to its popularization in the current American marketplace.

Randomized and Controlled Therapeutic and Prevention Trials With Echinacea Extracts for Upper Respiratory Tract Viral Infections
Recent clinical trials of commercial E. purpurea fresh plant liquid preparations and extracts have been well publicized and consistently demonstrate efficacy against acute upper respiratory tract viral infections. A 2007 meta-analysis40 of 14 studies among various Echinacea products evaluated randomized, controlled trials that studied a total of 1,356 patients for incidence and 1,630 patients for duration of the common cold. It showed that the use of these preparations decreased the chance of developing a cold by 58% and reduced the duration by a mean of 1.4 days. The 14 preparations in the meta-analysis included seven from E. purpurea, four from a combination of E. purpurea and E. angustifolia, one from E. angustifolia only, one from E. pallida, and one from an unidentified species. Significant reductions in occurrence and duration of the common cold were observed based on a subgroup analysis limited to five E. purpurea aerial plant juice investigations.
A 2006 systematic review41 of 16 randomized, controlled trials for the common cold was performed for heterogeneous Echinacea preparations. In two prevention trials, 411 subjects received Echinacea products, while five trials involved self-treatment (1,064 subjects), and nine trials studied clinically treated upper respiratory tract viral infections (1,126 subjects). This review identified no preparation with evidence of benefits for prevention but concluded that preparations based on E. purpurea aerial parts may be effective for early treatment of colds. Because other preparations were not phytochemically comparable, variations in the studies provided no clear evidence of their efficacy.
The single, randomized, placebo-controlled, double-blind study42 of E. angustifolia performed using three noncommercial extracts of two-year-old fresh roots to prevent or treat colds induced by rhinovirus type 39 in 399 volunteers was possibly the most publicized investigation; this study was funded by the US National Institutes of Health (NIH), and results were published in the New England Journal of Medicine. These extracts, made with supercritical carbon dioxide, 60% ethanol, or 20% ethanol, produced no tendency toward improvement when used for one week after virus exposure. For volunteers treated one week before and one week after exposure, clinical colds developed in 50% of participants receiving the 20% ethanol extract, in 57% receiving the 60% ethanol extract, in 62% receiving the supercritical carbon dioxide extract, and in 66% receiving placebo. The mean total symptom score was 12.1 for patients receiving the 20% extract, 13.2 for those receiving the 60% ethanol extract, 15.5 for those receiving the supercritical carbon dioxide extract, and 15.1 for those receiving placebo. However, none of the differences were statistically significant compared with placebo.
This study42 has been criticized for insufficient dosage (900 mg of root extractives vs. recommendations of a daily dose of 3 g by the World Health Organization and the Canadian Natural Health Product Directorate), inadequate validation of species identity, and limitation to one of more than 100 subtypes of rhinovirus.43 However, the daily dose in an E. pallida study44 of 160 patients with flu-like infections was extracted from 900 mg of root, which significantly reduced the illness duration, symptom scores, and clinical scores compared with placebo.
Although two authors of the NIH study42 had previously acknowledged that the geographic location of growing E. angustifolia and the time of its harvest affect the chemical composition,45 neither of these factors was described in the 2005 study42 in characterizing the roots obtained from a German company (presumably cultivated in Europe). While the supercritical carbon dioxide extract contained 74% alkamides and no polysaccharides or caffeic acid derivatives, the 60% ethanol extract had an uncharacteristically high 49% total polysaccharides, 2.3% alkamides, and 0.16% cynarin.42 The 20% ethanolic extract with 42% polysaccharides and 0.1% alkamides contained no caffeic acid derivatives. The polysaccharide content was not profiled on the basis of molecular weight but only on relative monosaccharide content, which is of no real value.
The high polysaccharide content of the 60% ethanol extract and the low or 0% content of caffeic acid derivatives (especially echinacoside) in all three extracts suggest that the roots used were not equivalent to “wild-crafted” roots traditionally favored and now used in some commercial echinacea products sold in North America. However, whether or not the lack of efficacy of these experimental E. angustifolia root extracts against a single rhinovirus subtype is accepted as legitimate evidence of its clinical effect on the common cold, this application is not representative of the traditional empirical use of this species.
On the other hand, success for prevention of the common cold was shown over a four-month period in a large randomized, double-blind, placebo-controlled study published in 2012. A total of 355 patients took a liquid 57% ethanolic extract of the fresh E. purpurea aerial plant (95%) and root (5%) (Echinaforce®, Bioforce; Roggwil, Switzerland) versus 362 taking a placebo. A dose of 0.9 ml, three times daily (from 2,400 mg herb/day) was used, except during acute stage of colds that developed when the dose was increased to five times daily (4,000 mg/day). The extract was diluted in water and held in the mouth for 10 seconds before swallowing. Though the extract group had a history of significantly greater susceptibility to cold infections, it had significantly fewer cold episodes and episode days (each 26% less). Recurrent infections were significantly decreased with echinacea extract (59% less), while use of concurrent pain medications aspirin, acetaminophen, and ibuprofen were also significantly fewer with the extract (52% less). There were no significant differences between adverse effects or tolerability between the two groups over the four-month period, indicating safe long-term use.46

Contraindications and Potential for Drug Interactions
The German Commission E monographs38 for the approved E. purpurea herb and E. pallida root and for the unapproved E. purpurea root, E. pallida herb, and E. angustifolia herb and root, speculate that risks warrant avoidance of use in cases of systemic diseases such as tuberculosis, multiple sclerosis, leukosis, collagenosis, AIDS or HIV infection, and autoimmune diseases. These contraindications remain controversial, as they are theoretical and not based on any actual clinical data. Reactions may occur in allergic individuals, especially when aerial parts are used.47
Legitimate concerns about combining Echinacea species preparations with pharmaceutical drugs are also largely speculative and are based on in vitro research. For example, as a precaution, patients undergoing organ transplantation who take immunosuppressive drugs, such as cyclosporine, should avoid the use of Echinacea preparations or should consider short-term use.46 Echinacea purpurea root extract (oral dose of 1.6 g/day) for eight days increased the clearance and reduced the bioavailability of intravenous midazolam when this cytochrome P450 (CYP) 3A4 substrate was administered to 12 subjects; the same dose of E. purpurea root extract did not alter oral midazolam clearance, suggesting that some extract components inhibit intestinal CYP3A, while other absorbed components induce liver CYP3A.48 In a 15-day open-label trial with 15 HIV patients receiving antiretroviral treatment with darunavir/ritonavir, 500 mg of E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma; Madrid, Spain) given every six hours for 14 days was well tolerated and did not significantly affect the drug pharmacokinetics.49 Echinacea angustifolia root tincture is a potent CYP3A4 inhibitor in vitro, more so than tincture of E. purpurea roots,50 but this has not been verified in human studies.
When an E. purpurea whole plant extract was given orally in a 1.6 gram daily dose to 12 healthy humans for 28 days, no significant effect on oral sedative midazolam was detected.51‡ An 8:1 extract of the whole fresh plant (Echinamide, Natural Factors Nutritional Products, Inc.; Everett, WA) was given in doses of 750 mg daily for 28 days to 16 healthy humans who were taking the antiretroviral combination drug lopinavir-ritonavir for 15 days prior and then 14 days with the extract. After the 14 combination days, there was no change in lopinavir bioavailability. After the extract had been administered for 28 days, single doses of fexofenadine and midazolam were administered; the midazolam bioavailability was significantly reduced, but fexofenadine pharmacokinetics were not significantly altered. This extract was shown to have a modest inducing effect on CYP3A as shown with midazolam, but not enough to counter the CYP3A inhibiting effect of ritonavir. It had no impact on P-glycoprotein efflux of fexofenadine.52
Most conventional pharmaceutical drugs, including the macrolide antibiotics clarithromycin and erythromycin, are metabolized by CYP3A4. A theoretical interaction between CYP3A4 substrates and E. angustifolia root tinctures is limited to in vitro data, while human research on the effects of E. purpurea root and whole plant extracts on this enzyme is equivocal; due to variations in preparations and outcomes, the current body of human research is too limited to predict pharmacokinetic or pharmacodynamic interaction outcomes with certainty, and little evidence exists to support significant clinical interactions with medications.53

Endangerment and Cultivation
The issue of sustainable harvest of wild-crafted E. angustifolia has been raised,54 yet it remains abundant in central Kansas, despite more than 100 years of commercial harvesting and digging booms.55 Because seeding in November yields the highest emergence for E. angustifolia plants in Nebraska,56 harvesting in the autumn and reseeding holes with the dry flower heads is a way to diminish loss from wildcrafting.
Echinacea angustifolia still grows over much of its historical range. Its global conservation status is ranked G4, i.e., “apparently secure.” In Kansas, where several generations of the same families have dug this species since the early 1900s, tagging pick-holes showed a regrowth potential of 36%, and measuring harvest density confirmed that the stands were not significantly diminished; areas that lay fallow for two-to-three years after harvesting allow more growth of the small roots and regrowth from remnants of larger harvested roots.57
Cultivation of Echinacea has increased rapidly because of the demand and its great value. Growth of the three major medicinal species, E. angustifolia, E. pallida, and E. purpurea, has been the most studied.58,59 Echinacea purpurea is easy to grow compared to the other two commercial species.59
Conclusions
The traditional clinical applications of E. angustifolia root hydroalcoholic extracts demonstrate their empirical usefulness. Simultaneous internal and local use was believed to increase efficacy. The historical use of E. angustifolia extracts to treat serious infectious diseases suggests that an advantage could be gained if they were given to complement conventional antibiotics. Clinical studies to investigate this possibility appear warranted, given the increasing incidence of antibiotic resistance.
However, positive evidence from clinical research on E. purpurea fresh plant liquid extracts for the treatment, and recently for the prevention, of upper respiratory tract viral infections has focused most attention in regard to commercial Echinacea species on this important use. Echinacea angustifolia also has been combined with E. purpurea in effective preparations for treating colds. Consequently, the recognition of E. angustifolia use for other infectious conditions has diminished, as conventional medicine inexorably depends on antibiotics.
Although sharing some similarities, selective use of Echinacea species, parts, and their preparations seems most appropriate for conditions established through empirical tradition (e.g., E. angustifolia root high-ethanol extracts internally and locally for treating sepsis, wounds, and bites) or through modern clinical research (e.g., fresh E. purpurea plant products for prevention and/or treatment of upper respiratory tract infections). The safety of Echinacea products is a major advantage, with few theoretical contraindications or individual allergic sensitivities. Echinacea popularity has resulted in regional overharvesting of wild E. angustifolia. Nonetheless, commercial cultivation of E. purpurea and conscientious wildcrafting can continue to provide a sustainable supply of these important botanical medicines.

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HerbalGram 97



Factors Affecting Echinacea Quality
W. Letchamo, L.V. Polydeonny, N.O. Gladisheva, T.J. Arnason, J. Livesey, and D.V.C. Awang

*We thank Jules Janick for his assistance with this manuscript. Herba Medica (Letchamo Naturals International) is thanked for sponsoring the scientific study, presentation, and publication of this manuscript.
Echinacea is a native of North America and traditionally used to combat cold, flu, cough, sore throats and many other ailments. Today, echinacea is among the most frequently utilized medicinal herbs around the world included in supplements and personal care formulations. The consumption of echinacea has significantly increased in Europe and North America, with a market share of about 10% of the herbal industry in the United States (Rawls 1996). In Russia, E. purpurea tops are mixed with animal feeds to improve the natural resistance of cattle to diseases, and improve milk production its quality. Numerous attempts have been underway in some non-traditional Echinacea growing countries, in Africa, Asia, Latin America, and the Middle East to introduce cultivation, processing, and marketing. Today, E. purpurea in the markets originates solely from cultivation, while E. angustifolia, E. pallida, E. paradoxa, E. tenneseensis, and E. sanguinea raw materials are sourced either from partial cultivation or totally collected from the wild.

Investigations of the pharmacological and biological activities of purported echinacea extracts have frequently shown them to be of widely differing character, with products obtained from either adulterated or misidentified species. With the evolution of botanical products, there has been an increasing demand for correctly identified herbal products that originate from cultivation. However, there has been little information on the influence of selected cultivars, various agronomic practices, and the geographical origin of the raw material. The objective of this study was to examine and demonstrate how factors such as growing conditions, geographic origins, diseases and pests, choice of the plant organ, and harvesting age (plant and flower ages) as well as the species contribute to the variations in the quality of different Echinacea species.

METHODOLOGY

Raw materials were obtained from various international and national sources, commercial herb growers and experimental stations. Selected plants were grown under similar field conditions in Trout Lake Washington, US from 1996 to 1998. We compared yield and quality of field- and hydroponically-grown plants. We determined product quality by measuring essential oil and caffeic acid derivatives such as cichoric acid, echinacoside, chlorogenic acid, and alkyl isobutylamides. HPLC chromatographic methods were based on Bauer et al. (1988) and Bauer and Remiger (1989) with slight modification. All plant parts were separated by hand, while seeds were separated using a seed thresher. Essential oil content was determined by subjecting 30 g of dried plant material to the standard hydrodistillation method for 2 hr, using Clevenger type apparatus.

THE WORLD SUPPLY OF ECHINACEA

Commercial cultivation of echinacea is mostly located in North-Western United States, and Western Canada (Table 1). Highest echinacea yields are reported in California (8500 kg/ha) and cichoric acid content of samples (2.29%) indicate an average yield of 195 kg/ha (Table 1). Austria, Germany, Russia, New Zealand, Ukraine, Yugoslavia, the Republic of South Africa (RSA) also have well-established cultivation of echinacea, though mostly E. purpurea or E. pallida. The highest cichoric acid content (4.93%), and calculated yield (276 kg/ha) was obtained from a Russian source, followed by samples grown in New Zealand (3.46%), Germany (2.86%, 212 kg/ha), and Austria (2.65%, 191 kg/ha).

The Russian geneticist N.I. Vavilov introduced E. purpurea from North America to Russia as early as 1924, while the first field production started in southern Russia in 1936 (A. Kodash, pers. commun., 1996). Further improvement and cultivation programs in Russia took shape during the early 1960s (Balabas et al. 1965). A Russian field study from 1971 to 1994 with two different populations (Ukrainian and Samaritan) of E. purpurea under Chernozem soil (black soil with 7%–9% organic matter content) indicates a positive influence of soil fertility on the concentration of cichoric acid (Gladisheva 1995). This may explain the relatively higher cichoric acid content in the Russian samples obtained either from Samara or Krasnodar region. E. purpurea cultivation extends as far as Ural mountains and Altai highlands in Siberia with an increasing tendency in size and processing capacity. Echinacea is widely adapted and can be grown under extremely varying climatic or vegetative conditions varying from 135 days in Siberia to 365 days in tropical/subtropical environments. It is important however that cultivars be selected for different ecological zones.

Brazil, Chile, Argentine, and Costa Rica have established field production of echinacea since 1998 (Table 1). Experimental fields of echinacea have been established in Egypt, Botswana, and Zambia. In Tanzania, echinacea is cultivated for export of off-season cut flowers to Europe. Presently the RSA has commercial production that supplies some of the Western European echinacea raw material, and prepares hydroalcoholic extracts based on cheaper sugarcane-based ethanol of African origin. Extracts are transported from the RSA to Europe and North American markets.

Table 1. Mean yield and content of cichoric acid in three year old Echinacea purpurea tops, cultivated under various ecological conditions, including hydroponically grown E. pupurea.

Country of origin Dry matter yield
(kg/ha) Cichoric acid content
(% dry matter) Calculated cichoric
acid yield
(kg/ha)
US
California 8500 2.29 195
Florida 5900 2.05 121
Montana ND 1.91 ND
Oregon 7080 2.13 151
New Mexico 6860 1.92 132
New York ND 1.72 ND
Washington 6820 2.11 144
Hydroponically grown tops 7840 2.10 165
Hydroponically grown roots 5321 2.21 118
Canada
Alberta 6200 1.87 116
British Columbia 6160 2.03 125
Ontario 6010 2.06 124
Quebec 5680 2.09 119
Europe
Austria 7200 2.65 191
Germany 7400 2.86 212
Finland 6090 2.39 146
Norway ND 1.88 ND
Yugoslavia 5990 2.07 124
Russia 5600 4.93 276
South America
Costa Rica ND 1.98 ND
Chile ND 2.05 ND
Africa
Egypt 5570 2.60 145
Tanzania 4600 2.06 95
South Africa (RSA) 5670 2.01 114
Botswana 4572 ND ND
Pacific
Australia ND 1.12 ND
New Zealand ND 3.46 ND
ND = Not determined

HYDROPONIC CULTIVATION

After 8 months of growth under hydroponic condition, E. purpurea yields were 7840 kg/ha with 2.10% cichoric acid content or 165 kg/ha (Table 1). Root yield was about 2.3 times as high as average of North American field production. This finding suggests that high quality echinacea tops and roots can be harvested from a hydroponic culture system within 6–8 months as compared to 36 months for field cultivation. Roots developed hydroponically were much easier to clean because of the absence of soil, stones, and weeds, had minimum microbial contamination, and few problems with soil born diseases. Fine roots that are known to contain higher cichoric acid concentration can be well maintained in a hydroponics system. During normal commercial root harvesting process from fields, about 12%–15% of the fine roots remain in the ground, while 17%–21% of the harvested thin roots are lost during root washing.

Hydroponic cultivation might prove valuable to reduce loss of chemical constituents, including polysaccharides, essential oils, and other hydrophilic components. Recent research findings suggest that the application of natural elicitors, such as chetosan, with simultaneous root aeration, can enhance the chemical yield compared to conventionally produced root samples (I. Raskin, pers. commun., series of lectures 2001).

DISTRIBUTION OF CICHORIC ACID, ISOBUTYLAMIDES, AND ESSENTIAL OIL

Relative distribution of cichoric acid and isobutylamides in different organs of E. purpurea, E. angustifolia, E. pallida and E. paradoxa is presented in Table 2. Ligulate florets showed the highest concentration of cichoric acid, while endosperm and seed coat had none. In some selected red or pink-flowered E. purpurea clones, cichoric acid content reached 12% but was lower in white-flowered E. purpurea (‘White Swan’) and E. pallida. Among 12 different lines of white-flowered E. purpurea ligulate florets, cichoric acid only reached 2.6%. The highest relative concentration of isobutylamide in all species was in seed coats followed by roots; it was not found in ligulate florets and endosperm. The highest essential oil content in all species was obtained from roots. E. paradoxa followed by E. pallida roots had the highest essential oil concentration; the lowest was obtained in E. purpurea. Results summarized in Table 3 are based on a mean data obtained during the 1996, 1997, and 1998 growing seasons. E. paradoxa and E. pallida roots might be good sources for essential oil production for specialized aromatherapy, personal care, and cosmetic applications. There were differences in the compositional profile of the hydrophilic and lipophilic components among the species investigated.

Table 2. Distribution of cichoric acid, isobutylamides, and essential oil in four different Echinacea spp. cultivated in Trout Lake Washington (1996–1998).

Compound Relative amount
Cichoric acid Ligulate florets>roots�leaves>root crown>tubular florets�stems>seed coat>endosperm
Isobutylamides Seed coat>roots>root crown>stems>tubular florets>leaves>ligulate florets=endosperm
Essential oils Roots>root crown�tubular florets�seed coat>leaves>ligulate florets=endosperm E. paradoxa�E. pallida>E. angustifolia>E. purpurea (results based on dried root samples)
Table 3. Influence of insects and diseases on cichoric acid and essential oil content in various populations of unselected echinacea species under organically certified field-growing conditions in Washington state.

Condition Cichoric acid content
(% of dry matter) Essential oil content
(% of fresh roots)
Echinacea purpurea
Healthy 2.01-2.68 0.12-0.38
Flower head borer infected 1.82 0.09
Root rot infected 1.02 0.01
Mycoplasma infected 0.88 0.00
Echinacea angustifolia
Healthy 0.02-0.49 0.56-1.13
Flower head borer infected 0.03 0.26
Root rot infected 0.02 0.11
Mycoplasma infected 0.00 0.00
Echinacea pallida
Healthy 0.09-0.21 1.78-2.03
Flower head borer infected 0.05 0.46
Root rot infected 0.01 0.23
Mycoplasma infected 0.02 0.63
Echinacea paradoxa
Healthy 0.32-0.57 1.24-2.43
Flower head borer infected 0.03 0.53
Root rot infected 0.02 0.31
Mycoplasma infected 0.00 0.60

DISEASES AND INSECTS

Echinacea was generally considered to have few or no disease or insect problems (Hobbs 1989). However, with increased cultivation practices, numerous diseases and insect problems occur, including cucumber mosaic virus, broad bean wilt, and mosaic diseases with flower phyllody symptoms due presumably to a mycoplasma-like organism (Fig. 1). Some of the diseases include shoot fungus (Cercospora sp.) (Fig. 2), root rot (Phymatotrichum omnivorum) on E. purpurea (Fig. 3), and E. angustifolia. Most of these problems have been identified to be widespread in organically certified commercial field cultivation (Table 3).


Fig. 1. E. purpurea infected by a mycoplasma-like organism in commercial fields.
Fig. 2. A slow but sure death of E. purpurea due to a leaf spot or shoot fungus (Cercospora sp.) infection is common in commercial cultivations.
Fig. 3. Root rot (Phymatotrichum omnivorum) of E. purpurea. Left: the beginning of root infection, see arrow. Right: advanced stage of the infection. Root rot is among the most common causes responsible for low quality commercially produced echinacea products.
Root rot infection on E. angustifolia usually appears during the second year of vegetation. During the first year, the infection does not show up either on shoots or roots. However, as plants age, infection spreads within the roots and invades neighboring plants. The use of susceptible lines, dense planting, and frequent irrigation can increase the incidence of disease.

Mystery of “Green Colored” Extracts

The problem of “green colored” E. angustifolia hydroalcoholic extracts has been a matter of speculation since 1995 in North American herbal industry. In fact, most vendors (bulk suppliers of certified organically grown roots) regarded this feature as a positive attribute and even promoted it as a “uniquely useful property” in their marketing campaigns. In our 1996–1998 field investigations and laboratory analyses, we found that in some organic commercial fields, root rot affected about 55%–60% of the second and third year E. angustifolia, and 30%–38% of E. purpurea plants. As the disease progresses, roots change color to dark brown, while the leaves wilt and die back very slowly (Fig. 4). Though the root may be infected, the plants can still grow beyond the first and second years. In most cases, however, infected roots are harvested and processed for marketing. The problem of “green colored extract” was mostly prevalent in roots originating from the “certified organically produced” echinacea. After the first week following extraction, the green extracts developed an offensive odor. The problem appears to be due to a fungal (bacterial) infection of the roots which contaminates the liquid extracts. Blanching or treatment of the samples with hot steam for 15 minutes before or after extraction did not solve the problem. The green color was not found when extracts were prepared from healthy root samples.

Insects

Sunflower moth (Homoesoma electellum) is one of the most common insects damaging E. purpurea and E. angustifolia flowerheads (Fig. 5). The females lay eggs on the bracts of developing flower buds. The larvae feed on the florets and pollen. Older larvae tunnel through immature seeds and flowerheads, resulting in extensive damage to the head, and creating secondary infections, fungal damage, head rot and attracting other opportunistic diseases to the whole plant. So far about 60% to 65% of the commercially grown E. purpurea and E. angustifolia in North-Western US have been found infected. Echinaceae pallida and E. paradoxa cultivated under experimental “certified organically grown” fields were observed to be infected with the above insects and microorganisms (Table 3). Significant reduction in the content of some of the chemical components indicated the need for resistant cultivars and choosing the right harvesting stage (Fig. 6).

As the number of growers attracted to organic cultivation increases, non-chemical prevention of plant diseases should be increasingly attractive. The selection of disease and pest resistant cultivars, implementing appropriate agronomic practices, including proper crop rotation, soil and water management programs, and establishing early detection and a removal system for infected plants, represent a sensible approach to a clean healthy product. However, as the effect of pathogenic toxins are unknown it is prudent to use approved pesticides and fungicides for disease and pest control.

GENETIC SELECTION AND IMPROVEMENT

Echinacea selection and breeding efforts could develop cultivars with higher root and shoot yield, suitable for mechanical harvesting, uniform growth, flowering, seed ripening, good leaf to stem ratios, and higher content of cichoric acid, isobutylamides, flavonoids, polysaccharides, and essential oil. The effect of genetic improvement on the chemical content of selected clones of E. purpurea ‘Sorgogo’ and E. angustifolia ‘Ergogo’ is shown in Table 4. The identification and development of E. purpurea cv. ‘Magical Ruth’ and the influence of flower developmental stages in its quality has been described earlier (Letchamo et al. 1999).

Table 4. Effects of plant selection and flower developmental stages on chemical content of E. purpurea and E. angustifolia clones under commercial cultivation in the US.

Flower
developmental
stages Content (% dry matter)
Cichoric acid Echinacoside Isobutylamides
Before
selection After
selection Before
selection After
selection Before
selection After
selection
E. purpurea 'Sorgogo'
1 (early) 2.56 3.97 0.002 0.007 0.008 0.011
2 (medium) 1.89 2.35 0.023 0.011 0.004 0.012
3 (mature) 0.39 0.76 0.034 0.081 ND 0.016
4 (overblown) 0.06 0.43 0.048 0.072 ND 0.015
Mean 1.23 1.88 0.027 0.043 0.006 0.014
E. angustifolia 'Ergogo'
1 (early) 0.26 0.65 0.016 0.056 0.038 0.048
2 (medium) 0.14 0.25 0.121 0.130 0.025 0.038
3 (mature) 0.10 0.08 0.245 0.605 0.019 0.039
4 (overblown) 0.07 0.03 0.168 0.587 0.032 0.036
Mean 0.14 0.25 0.135 0.344 0.029 0.040
ND = Not determined

The effect of selection was evaluated for E. purpurea ‘Sorgogo’ and E. angustifolia ‘Ergogo’ for cichoric acid, echinacoside, and isobutylamides (Table 4). Selected clones before and after selection were measured in four stages of flower development. In all cases selection increased the content of measured constituents. Maximum content of cichoric acid was found in stage 1 (early) while the maximum echniacoside echniacoside content was found in stage 3 or 4 (mature and overblown). There was narrow developmental stage based difference for isobutylamides.

Results of four years of field experiments with locally adapted and partially improved E. purpurea seeds in Russia (Moscow region) are presented in Table 5. The highest cichoric acid content in leaves (5.37%), and roots (5.46%) was obtained during the first year at the end of vegetation. During the second, third, and fourth years of vegetation, the highest concentration of cichoric acid in leaves, stems, inflorescence, and roots was found at the massive bud formation stage.

Table 5. Developmental variations in cichoric acid content in E. purpurea grown in Russia.

Developmental stages Cichoric acid content (% of dry matter)
Leaves Stems Inflorescence Roots
1st year of vegetation 1994
1st year leaves 5.14 NA NA 3.55
Stem development 4.69 NA NA 4.00
End of vegetation 5.37 NA NA 5.46
Massive bud formation 5.47 1.79 NA 4.83
2nd year of vegetation 1995
Massive flowering 5.31 1.74 4.50 4.75
Seed ripening 4.52 1.57 NA 3.64
End of vegetation 4.91 NA NA 4.15
Massive bud formation 6.74 2.28 NA 4.37
3rd year of vegetation 1996
Massive flowering 5.68 2.06 2.85 3.26
Seed ripening 4.50 1.27 NA 3.24
End of vegetation NA NA NA 4.00
Massive bud formation 6.41 2.70 NA 3.50
4th year of vegetation 1997
Beginning of flowering 6.34 1.20 3.06 2.92
Massive flowering 5.05 1.37 3.34 3.43
End of vegetation NA NA NA 3.12
NA = Not available

CONCLUSIONS

The chemical composition of echinacea raw material is of interest to both the herbal industry and regulatory agencies as a determinant of product quality and authenticity, with an end towards to protecting consumers from low quality or fraudulent products. The degradation of the chemical constituents during E. purpurea processing has been well known (Bauer 1998; Livesey et al. 2000). Results were obtained from various investigations in 1996–1998 that were conducted with numerous clones, and accessions developed under different agronomic and processing practices (W. Letchamo, unpubl. 1998). Our investigation indicated that unique cultivars with various levels of chemical constituents, resistance, freedom from diseases and pests, and yield can be developed within a short period of time. Based on those findings, we suggest establishing 2.2% cichoric acid content as a minimum standard for any commercial E. purpurea raw material the can be processed for health applications.

So far most of the chemical and clinical studies of echinacea products have been done using plant samples of unknown origin, cultivation, cultivar, health status of plants and questionable agronomic practices. Therefore, it is highly recommended that future medical or clinical studies on efficacy, safety, and toxicity of echinacea be based on known healthy cultivars, standard agronomic practices, specific plant developmental stages, and geographic sources. By doing this, it will be possible to protect consumers from hidden health dangers from microbial and fungal toxic metabolites.

REFERENCES

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