Echinacea angustifolia
Synonyms
No documentation
Vernacular Name
Purple coneflower, blacksamson, snakeroot, narrow-leaved purple coneflower, black susans[1],[2],[3]
Description
Echinacea angustifolia is one of several species of Echinacea and is identifiable by the sunflower-like appearance of its lavender-colored flowers and narrow leaves. E. angustifolia belongs to the Asteraceae family and is native to the United States of America and Canada.[1] Historically, E. angustifolia roots were used by indigenous North Americans to treat infections and wounds.[4] E. angustifolia has been employed as an immunomodulatory agent due to its ability to enhance the body’s natural defenses against pathogens. As a result, E. angustifolia is marketed commercially for the treatment of viral infections including, but not limited to, the common cold and upper respiratory tract infections.
E. angustifolia is a member of the Asteraceae family also known as coneflowers. The plant grows from a taproot to about up to 150cm. in height and produces a large head of composite flowers during summer season. These flowers range from purple to pinkish-purple. This erect plant is not branched and has alternate lanced leaves that are hairy and rough in texture.
Origin / Habitat
E. angustifolia is native to North America and is cultivated as a perennial for gardens and grown for its medicinal use. They grow in moist to dry conditions with full sun and can easily winter over in the colder regions. Native growth includes prairies and lightly wooded areas.
Chemical Constituents
Caffeic acid derivatives (e.g. echinacoside), Alkylamides (e.g. dodeca-2Z,4E,10Z-trien-8-ynoic acid isobutylamide), Polysaccharides (e.g. inulin), Polyynes (e.g. trideca-1-en-3,5,7,9,11-pentaine), Glycoproteins (arabinogalactan proteins).[3],[6],[7],[8]
Plant Part Used
Medicinal preparations are made from the root and rhizome; E. angustifolia preparations may be found in the form of teas, tablets, capsules, and powders.[3],[5]
Medicinal Uses
General
Prophylaxis and treatment of upper respiratory infections (URIs) and additional infections of varying etiologies.[3],[4],[9],[10]
Analgesic and treatment of inflammatory conditions, chemotherapy adjunct, and enhanced wound healing by external application to wounds.[11],[12],[13]
Most Frequently Reported Uses
Prophylaxis and treatment of upper respiratory infections (URIs) and additional infections of varying etiologies.[3],[4],[9],[10]
Dosage
Dosage Range
Quantity dried equivalent of root/rhizome for adults: 1.0g per day to 3.0 g per day.[5] Some clinicians recommend a dosing cycle. For example, use Echinacea for 3 weeks, refrain from use for 1 week and begin again. Alternatively, use for 8 weeks followed by 1 week off.
Most Common Dosage
Acute use: 500 mg (standardized extract) taken 3 times a day for the first day; from the second day onward, 250mg taken 4 times a day. For prevention: 250mg (standardized extract) taken 2 times a day; a dosing cycle may be employed as discussed above.
Standardization Dosage
E. angustifolia is standardized to 4% echinacosides
Pharmacology
Pre-clinical
The Ethnomedicinal practices have employed E. angustifolia preparations in the treatment of a variety of immune-related illnesses. Recent laboratory investigations that have utilized animal models in experimental studies designed to assess immunomodulatory activity have provided support for the use of E. angustifolia and/or its constituents as immunomodulatory agents. It is theorized that the Echinacea species produces its effects through modulation of multiple immunological parameters, e.g. through production of increased phagocytosis, in order to ultimately produce enhanced nonspecific cellular immunity. The ethanol extract of E. angustifolia has been shown to modulate macrophage function through its ability to attenuate the production of nitric oxide and tumor necrosis factor-alpha in lipopolysaccharide-activated RAW 264.7 murine peritoneal macrophages.[14]
A controversy amongst researchers regarding the potential for nonspecific responses of immunocompetent cells led to an investigation utilizing a standardized hydroethanolic extract from E. angustifolia roots that was lipopolysaccharide-free; the study affirmed the ability of E. angustifolia to enhance cell-mediated immune function through its observed actions on T-lymphocyte proliferation and interferon-gamma production.[15] In vivo studies have demonstrated that extracts of E. angustifolia possess immune stimulating activity in the murine model; treatment with extract of E. angustifolia reduced Candida albicans-induced mortality in healthy and cyclosporine-A treated mice.[15] Equine in vivo studies established E. angustifolia extract as an agent capable of stimulating immunocompetence through modulation of nonspecific cellular immunological parameters; treatment with E. angustifolia root extract for six weeks increased phagocytic activity, elevated peripheral lymphocyte counts, increased the size and concentration of peripheral red blood cells whilst also increasing hemoglobin concentration in healthy horses.[16] A human study assessing an E. angustifolia intravenous homeopathic complex preparation demonstrated an enhancement in the phagocytic activity of polymorphonuclear neutrophil granulocytes when compared to placebo and adverse effects could not be detected.[17]
Analysis of ethanol extracts taken from E. angustifolia, E. pallida, and E. purpurea has shown variability between the species with regard to concentrations of hydrophilic caffeic acid derivatives and lipophilic amides.[18] These differences have physiological relevance as the constituent concentration impacts the observed magnitude of an Echinacea-induced biological action; for example, it was found that ethanol extracts of E. angustifolia, E. pallida, and E. purpurea all enhanced interferon-gamma production by mouse splenocytes stimulated in vitro by Concanavalin A whilst only E. angustifolia and E. pallida increased interleukin-4 and interleukin-10 in splenocytes by 3 to 4-fold.[18] It appears that the effects of E. angustifolia on macrophages may be multifaceted; E. angustifolia has been shown to increase arginase activity of macrophage cells stimulated with 8-bromo-cAMP whilst suppressing nitric oxide production thereby maintaining biological balance whilst producing an enhancement in nonspecific cellular immune function.[14] Further investigation revealed that the polar fraction of E. angustifolia containing the caffeic acid derivatives produced the enhancement of arginase activity, whilst the lipophilic fraction containing the alkamides suppressed nitric oxide production.[14] This finding is consistent with earlier research that has demonstrated the ability of alkamides isolated from E. angustifolia to mediate anti-inflammatory activity.[6] In vivo studies with mice have shown a polysaccharidic fraction of E. angustifolia to inhibit carrageenan-induced paw edema and croton oil-induced ear edema indicating that the anti-inflammatory effect of E. angustifolia is likely attributable to its multiple constituents.[12]
It appears that the immunomodulatory activity associated with Echinacea use is likely attributable to multiple mechanisms of action. Echinacea-induced increases in anti-inflammatory cytokines and the Echinacea-induced decrease in tumor necrosis factor-alpha observed in activated splenocytes indicate that Echinacea may act as an immunomodulatory agent by altering the ratio of anti-inflammatory cytokines to pro-inflammatory cytokines.[18] In vitro assays with human neuroglioma cells (H4) have demonstrated that E. angustifolia extract suppressed cyclooxygenase-2 dependent prostaglandin-E2 formation at sites of inflammation; alkamides isolated from E. angustifolia root extract are important constituents for contributing to the Echinacea-induced pharmacological anti-inflammatory effects as they have been shown to interfere with cyclooxygenase-2 activity.[11] As the alkamides have been shown to exhibit affinity for cannabinoid receptors, especially cannabinoid receptor subtype 2, the interactions between alkamides from E. angustifolia, the endocannabinoid system, and its associated cascades, may contribute to the immunomodulatory effects of E. angustifolia.[19] In vivo studies utilizing rats have indicated that E. angustifolia -enhanced immune function may be attributable to Echinacea-induced antigen-specific immunoglobulin production as treatment with Echinacea augments rat primary and secondary immunoglobulin-G response in antigen-challenge experiments.[20]
The studies completed in ruminants have shown that incubation of a standardized extract of E. angustifolia with bovine peripheral blood mononuclear cells increases proliferation in a dose-dependent manner and extracts of E. angustifolia produce concentration-dependent inhibition of adhesion and superoxide production whilst stimulating production of interleukin-8 in ovine neutrophils.[21],[22] Furthermore, ovine neutrophils preincubated with E. angustifolia extract have shown E. angustifolia to reduce spontaneous apoptosis, when compared to control apoptotic rates.[22] This finding is of clinical importance with regard to use of Echinacea as an adjunct to chemotherapy; a study investigating concomitant E. angustifolia root extract with doxorubicin chemotherapy demonstrated manifestation of both proliferative and antiproliferative activity in cervical and breast cancer cells dependent upon the specific cell line and treatment with E. angustifolia or its phenolic constituents.[23] These results may be an indication that standardized extracts could be useful adjuncts to chemotherapy but their ability to interfere with chemotherapy necessitates further study.
E. angustifolia extract has been shown to be cytotoxic in human pancreatic and colon cancer cell lines (MIA PaCa-2 and COLO320, respectively) thereby providing additional support for the use of Echinacea in oncology.[24] Murine and bovine (HC11 and BME-UV, respectively) cell lines have also been employed to assess the biological effect of E. angustifolia treatment upon normal cell viability and differentiation.[25] The results indicate that treatment with E. angustifolia produces an enhancement in cell viability; further experiments indicate that the proposed mechanisms by which the stimulation of mammary epithelial cell physiology occurs may be through increased MAPK and AKT activation or through the dose-dependent reduction of caspase 3 activities that ensures following E. angustifolia treatment.[25] Taken together, the effects of E. angustifolia may have therapeutic implications in the treatment of inflammation-related pathologies, oncology and autoimmune disorders.
One constituent of E. angustifolia, echinacoside, has been investigated for its role in the wound healing properties of Echinacea reported in ethnomedicinal studies. One such study utilized unilateral vocal fold stripping to induce porcine vocal fold injury with the uninjured vocal fold serving as control.[13] A standardized extract of Echinacea was employed to evaluate the effects of echinacoside and its established anti-hyaluronidase properties on wound healing by topically applying the extract to the injured vocal fold; when compared to control, topical application of the standardized extract of Echinacea improved vocal economy and phonation threshold pressure.[13] The resulting improvements served to support the traditional practice of using Echinacea for enhanced wound healing.
The preclinical studies provide support for the immunostimulatory effects associated with Echinacea use; clinical trials assessing Echinacea preparations in the prophylaxis and treatment of upper respiratory infections have demonstrated favorable differences in the treatment versus control groups.[26],[27] The conflicting conclusions of these studies may be attributable to varying factors within the experimental designs, such as the use of different doses and/or preparations of Echinacea, different animal models employed, and/or differing parameters measured to evaluate outcome in patients. The discrepancy in findings may also be due to failure of Echinacea products to meet recognized pharmaceutical quality standards.[26] The immunostimulatory activity of Echinacea preparations has been found to vary significantly by preparation and even raw material obtained from the same supplier varied greatly by lot when examined for immunostimulatory activity.[28] This occurrence may explain why some studies have shown immunostimulatory activity to be specific to Echinacea herb and root powder preparations whilst others have demonstrated that the extracts display immunostimulatory activity.[28],[17] Indeed, product variation with regard to species of Echinacea and formulation utilized was found to vary greatly between ten commercially available preparations of E. angustifolia or Echinacea purpurea when assessed by phytochemical analysis.[29] These variations produced differences in constituent content; E. angustifolia products derived from ethanolic extracts displayed a low polysaccharide profile and high levels of alkamides, echinacoside, and cynarin. This constituent profile was consistent amongst ethanol-derived preparations of Echinacea and associated with high antiviral activity but limited immunostimulatory activity.[29] On the contrary, products derived from aqueous extractions displayed high levels of polysaccharides, low levels of other constituents, and immunostimulatory activity in a mouse macrophage model.[29]
Clinical
Reviews of available literature detail the clear controversy regarding the clinical effectiveness of Echinacea; several studies have shown Echinacea to be effective in the prophylaxis and/or attenuation of illnesses such as the common cold, while several other studies have reported no clinical benefits.[30],[31],[32],[33]
Interaction and Depletions
Interaction with other Herbs
No documentation
Interaction with Drugs
Agents with potential or established hepatotoxicity (e.g. alcohol, methotrexate,
acetaminophen/paracetamol, naltrexone, phenothiazines, black cohosh etc.)
Immunosuppressive agents (e.g. corticosteroids, cyclosporine)
Non-steroidal anti-inflammatory agents (e.g. aspirin, ibuprofen)
Chemotherapeutic agents
Interferon preparations
Antimicrobial agents
Antiplatelet agents
Anticoagulant agents
Agents with antioxidant activity
Precautions and Contraindications
Side effects
Patients possessing allergies to members of the Asteraceae family (e.g. sunflower, safflower, ragweed, chamomile and mugwort) should use E. angustifolia with caution due to an established cross-reactivity between members within this family. Allergic reactions have been documented in individuals with sensitivities to other members of the Asteraceae family following use of Echinacea; following exposure to Echinacea, allergic patients present with symptoms that range in severity from localized symptoms (rhinitis and/or urticaria) to acute asthma attack to generalized, life-threatening anaphylaxis.[26],[37],[38],[39] As with all allergies, incidence of allergic reactions is higher in patient populations where asthma or atopy are already present and patients should consult their medical practitioner/seek medical attention if allergic symptoms manifest. [37],[38]
Parental administration of Echinacea preparations has produced adverse reactions, including but not limited to urticaria, pyrexia and muscle weakness.[45] Patients suffering from kidney, liver, immunosuppressive or chronic diseases should not begin any medicinal therapy without a consultation with their medical practitioner. Echinacea is theoretically contraindicated in patients suffering from autoimmune diseases although there is a paucity of scientific evidence available to support this theory.[27],[44] Echinacea preparations have produced transient lymphopenia in patients afflicted with infections of various etiologies and so should not be used in patients with active infections.[45] Patients should always inform their medical practitioner about any herbal supplements and/or vitamins that the patient is taking and consult with their medical practitioner before beginning any novel treatment.
Pregnancy
Patients planning to become pregnant, who are pregnant or breastfeeding should not use Echinacea supplements without first consulting their medical practitioner due to the lack of information concerning the use of supplements during pregnancy and lactation.[40] A review of available literature assessing information regarding the safety and efficacy of Echinacea species supplements during pregnancy and lactation concluded that oral consumption of Echinacea during the first trimester did not appear to increase the risk for major malformations but preparations should be used with caution during lactation due to insufficient information.[37],[41]
Age limitation
E. angustifolia supplements should not be used in pediatric patients without first consulting a medical practitioner due to the insufficiency of scientific studies specific to the pediatric population. Echinacea (purpurea) treatment demonstrated no difference in duration of URI, severity of URI symptoms, or number of days where fever was present during the URI for pediatric patients aged 2-11 when compared to placebo.[42] Importantly, the investigation found an increased incidence of rash in the pediatric patients treated with Echinacea (purpurea) when compared to those receiving placebo; therefore, caution is recommended if using Echinacea supplements in a pediatric patient.[42]
Adverse reaction
A clinical study that showed continuous therapy with Echinacea produced greater immune reactivity with longer duration of use, i.e. immune reactivity was greatest after 10 weeks of use when compared to levels at 2 weeks of use, has been cited in support of increased immune reactivity with longer durations of use.[43],[44] A double-blind, placebo-controlled randomized trial assessed the use of E. angustifolia extract over a period of 12 weeks and concluded that oral administration of Echinacea for a period up to but not exceeding 12 weeks produced no significant increase in adverse effects when compared to the number of adverse effects reported by the placebo group.[9] Similarly, there was no difference in the number of reported adverse events between E. angustifolia treatment groups and placebo during a 7-day prophylaxis or 5-day treatment study employing challenge with rhinovirus type 39.[4] The long term use of Echinacea, i.e. durations of use that exceed 12 weeks, has not been evaluated to date and clinical studies that have assessed E. angustifolia are few in number.
Oral preparations of Echinacea are generally regarded as safe due to the minimal calculated risk short-term use of quality products pose to consumers when factors such as the number of patients using Echinacea and the number of doses consumed annually are compared to the low numbers of reported adverse events.[27],[34],[35]
Echinacea species appear to have low potential to produce cytochrome P450 drug-herb interactions; and adverse effects, when they manifest, are typically transient and reversible.[7],[34],[36],[37] However, the use of Echinacea for extended periods of time is a matter of debate and conflicting studies are found in the literature with regard to this topic.
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References
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