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PubMed2002

Genetic relationships and diversity of commercially relevant Echinacea species.

The genus Echinacea is comprised of nine species, which are perennial herbs indigenous to North America and which have been traditionally used as medicinal plants for centuries. Three Echinacea species, E. angustifolia, E. purpurea, and E. pallida, are currently being traded internationally in the natural products market. Echinacea products constitute a significant portion of this growing, multi-billion dollar industry. The increasing popularity of Echinacea products has led to the expansion of wildcrafting and commercial cultivation to meet the growing demand for plant material. Echinacea is considered of value as a nonspecific immune stimulant, and claims of its efficacy have been tentatively supported by both laboratory and clinical studies. This study used random amplified polymorphic DNA (RAPD) markers to determine the genetic relationships of the three Echinacea species of commercial interest, to evaluate the level of diversity present within germplasm of each of the three species, and to compare accessions of each species available from different sources. A total of 101 RAPD markers were generated for the 76 individuals of four species included in the analysis. NTSYS-pc was used to evaluate the genetic relationships of the three species and to determine the general level of overall diversity. Analysis of molecular variance (AMOVA) was performed using pruned marker sets corrected for the dominant nature of RAPD markers. AMOVA revealed that most of the variation occurred within accessions of the same species, though some accessions of both E. pallida and E. angustifolia were found to be significantly different from other accessions of the same species.

Journal Article↗
PubMed1997

Echinacea-induced cytokine production by human macrophages.

Echinacea purpurea, a plant originally used by native Americans to treat respiratory infections, was evaluated for its ability to stimulate the production of cytokines by normal human peripheral blood macrophages in vitro. Commercial preparations of echinacea fresh pressed juice and dried juice were tested at concentrations ranging from 10 micrograms/ml to 0.012 microgram/ml and compared to endotoxin stimulated and unstimulated controls. Cytokine production was measured by ELISA after 18 h of incubation for IL-1 and 36 and 72 h for TNF-alpha, IL-6, and IL-10. Macrophages cultured in concentrations of echinacea as low as 0.012 microgram/ml produced significantly higher levels of IL-1, TNF-alpha, IL-6 and IL-10 (P < 0.05) than unstimulated cells. The high levels of IL-1, TNF-alpha, and IL-10 induced by very low levels of echinacea are consistent with an immune activated antiviral effect. Echinacea induced lower levels of IL-6 in comparison to the other cytokines measured. These results demonstrate the immune stimulatory ability of the unpurified fresh pressed juice of Echinacea purpurea and offer some insight into the nature of the resulting immune response as compared to endotoxin.

Adjuvants, Immunologic↗
PubMed2005

Changes in immunomodulatory properties of Echinacea spp. root infusions and tinctures stored at 4 degrees C for four days.

BACKGROUND: Phytomedicinal preparations from members of the genus Echinacea are popular worldwide and frequently used to treat upper respiratory infections. With the increasing popularity of herbal medicines, many people are making their own Echinacea extracts at home and storing them at refrigerator (4 degrees C) temperatures. We tested the hypothesis that Echinacea extracts made using homemade methods change in immunomodulatory efficacy with storage at 4 degrees C over a 4-day period. METHODS: Three extract types (50% ethanol tincture, cold water infusion, hot water infusion) from 5 different species (Echinacea angustifolia, E. pallida, E. purpurea, E. sanguinea, E. tennesseensis) were prepared. Four in vitro immune assays (monocyte secretion of TNF-alpha, IL-10, and IL-12; and peripheral blood mononuclear cell proliferation) using human blood were used to test extract efficacy at Days 1 and 4 post-extraction. Two statistical analyses, traditional ANOVA and several statistical models that account for endotoxin effects, were used. RESULTS: Endotoxin was found to significantly impact immune outcomes only in 4-day old cold water infusions and not in all assays. Extracts showed the greatest stimulation in TNF-alpha assays. By extract type, 50% ethanol tinctures produced the most immune stimulation. By species, extracts from E. angustifolia extracts were the most efficacious in our assays; extracts from E. sanguinea showed the least activity overall. CONCLUSIONS: Taken together, these results suggest that: (1) homemade Echinacea extracts are efficacious in modulating immune cell activity in vitro but that their properties change with time during storage at 4 degrees C; and (2) endotoxin effects from extracts may be important considerations in the analysis of immunobiological data.

Cell Proliferation↗
PubMed2006

Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells.

Alkylamides present in Echinacea species have reported immunomodulatory actions, yet their direct effects on T lymphocytes, key mediators of antiviral immunity, are poorly understood. We hypothesized that constituents present in ethanolic extracts of Echinacea species exert direct immunomodulatory effects on human Jurkat T cells. Modulation of IL-2 production by submaximally stimulated Jurkat cells was determined in response to treatment with extracts prepared from dried aerial parts of Echinacea purpurea. Cells were treated with the extracts, with alkylamides or caffeic acid derivatives isolated from Echinacea species, or with corresponding ethanol vehicle, in the absence or presence of phytohemagglutinin and phorbal ester. E. purpurea extracted in a solvent mixture of 95:5 ethanol/water dose-dependently inhibited IL-2 production. This IL-2 inhibitory activity correlated with the presence of alkylamides but not caffeic acid derivatives, as determined by high performance liquid chromatography/electrospray ionization-mass spectrometry analysis. Simultaneous measurement of secreted IL-2 by ELISA and cell viability by the XTT assay showed that the 95:5 ethanol/water extract of E. purpurea was both IL-2 suppressive and cytotoxic at 50 and 100 microg/mL. Lower concentrations from 6.25 to 25 microg/mL significantly decreased IL-2 production but not cell viability. Alkylamides at concentrations found in a 50 microg/mL extract decreased IL-2 production by approximately 50%. Two Echinacea-derived alkylamides significantly depressed IL-2 production but not cell viability in a dose-dependent manner. Thus, alkylamides present in E. purpurea suppress the ability of activated Jurkat T cells to produce IL-2 independently of direct, cytotoxic effects.

Amides↗
PubMed2000

Light-mediated antifungal activity of Echinacea extracts.

This study demonstrated that plant extracts containing acetylenic isobutylamides and polyacetylenes, previously reported as occurring in Echinacea, have phototoxic antimicrobial activity against fungi, including clinically relevant pathogenic fungi. Results show that hexane extracts of Echinacea variably inhibit growth of yeast strains of Saccharomyces cerevisiae, Candida shehata, C. kefyr, C. albicans, C. steatulytica and C. tropicalis under near UV irradiation (phototoxicity) and to a lower extent without irradiation (conventional antifungal activity). The presence of polyacetylenes and alkylamides in extracts of different organs was confirmed in Echinacea purpurea by HPLC in agreement with previously reported data in the literature, and was related to phototoxic activity. Two representative pure compounds, undeca-2E,4Z-diene-8,10-diynoic acid isobutylamide and dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide, were isolated from Echinacea purpurea root extracts, and compared in a disk assay (5 micrograms/disk) with the highly conjugated trideca-1-ene-3,5,7,9,10-pentayne (previously isolated in our laboratory and found here in E. purpurea). Significant phototoxicity was demonstrated by pure trideca-1-ene-3,5,7,9,10-pentayne, while only minor phototoxicity was induced by the other two acetylenic compounds. Phototoxic activity of Echinacea spp. is primarily attributed to the ketoalkenes and ketoalkynes abundantly present in the roots.

Antifungal Agents↗
PubMed2004

Monoclonal antibodies against an arabinogalactan-protein from pressed juice of Echinacea purpurea.

Pressed juices of the aerial parts of Echinacea purpurea are used as non-specific immunostimulants, and arabinogalactan-proteins (AGPs) have been shown to be part of the active principle. Monoclonal antibodies against an AGP from pressed juice of Echinacea purpurea with complement-stimulating activity have been established by means of hybridoma techniques. To test the specificity of the antibodies, several other arabinogalactan-proteins from suspension cultures of Echinacea purpurea, the roots of Echinacea pallida, the aerial parts of Rudbeckia hirta, the roots of Baptisia tinctoria and gum arabic as well as an arabinogalactan from larch wood were tested in a competitive ELISA for cross reactivities. Chemical modifications at the periphery of the AGP molecules either by reduction of uronic acids or by dearabinosylation had no influence on the reactivity of the molecules towards the antibodies. For further characterization of the epitope, different Ara-Gal-oligosaccharides were used as antigens. A hexasaccharide consisting of a backbone of four molecules of 6-linked beta- D-Gal p, the second and the fourth of them branched at O-2 to an alpha- L-Ara f residue showed weak but reproducible cross reactivity, indicating that the antibodies may be at least in part directed to the carbohydrate moiety of the AGP. Testing of anti-AGP antibodies JIM 8 and LM 2 revealed good reactivity of LM 2 with the Echinacea AGP, whereas Jim 8 showed only very weak interaction.

Animals↗
PubMed2006

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

The medicinal plant Echinacea is widely used to treat upper respiratory infections and is reported to stimulate the human immune system. A major constituent class of Echinacea, the alkylamides, has immunomodulatory effects. Recent studies show that alkylamides are oxidized by cytochrome P450 enzymes, but the immunomodulatory activity of these products is unknown. The objectives of this study were to characterize the products formed by incubation of an Echinacea extract and an isolated alkylamide with human liver microsomes, and to evaluate the influence of Echinacea alkylamides and metabolites on cytokine production by Jurkat human T cells. A novel class of carboxylic acid alkylamide metabolites was identified and shown to be the major constituents present after 2-h incubation of alkylamides with human liver microsomes. Echinacea alkylamides suppressed IL-2 secretion by stimulated T cells, and this effect was significantly lessened upon oxidation of the alkylamides to carboxylic acids and hydroxylated metabolites. These findings highlight the importance of considering the influence of liver enzyme metabolism when evaluating the immunomodulatory effects of alkylamides.

Cell Line↗
PubMed2005

An evaluation of Echinacea angustifolia in experimental rhinovirus infections.

BACKGROUND: Echinacea has been widely used as an herbal remedy for the common cold, but efficacy studies have produced conflicting results, and there are a variety of echinacea products on the market with different phytochemical compositions. We evaluated the effect of chemically defined extracts from Echinacea angustifolia roots on rhinovirus infection. METHODS: Three preparations of echinacea, with distinct phytochemical profiles, were produced by extraction from E. angustifolia roots with supercritical carbon dioxide, 60 percent ethanol, or 20 percent ethanol. A total of 437 volunteers were randomly assigned to receive either prophylaxis (beginning seven days before the virus challenge) or treatment (beginning at the time of the challenge) either with one of these preparations or with placebo. The results for 399 volunteers who were challenged with rhinovirus type 39 and observed in a sequestered setting for five days were included in the data analysis. RESULTS: There were no statistically significant effects of the three echinacea extracts on rates of infection or severity of symptoms. Similarly, there were no significant effects of treatment on the volume of nasal secretions, on polymorphonuclear leukocyte or interleukin-8 concentrations in nasal-lavage specimens, or on quantitative-virus titer. CONCLUSIONS: The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it.

Adult↗
PubMed2004

Echinacea purpurea for prevention of experimental rhinovirus colds.

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the ability of Echinacea purpurea to prevent infection with rhinovirus type 39 (RV-39). Forty-eight previously healthy adults received echinacea or placebo, 2.5 mL 3 times per day, for 7 days before and 7 days after intranasal inoculation with RV-39. Symptoms were assessed to evaluate clinical illness. Viral culture and serologic studies were performed to evaluate the presence of rhinovirus infection. A total of 92% of echinacea recipients and 95% of placebo recipients were infected. Colds developed in 58% of echinacea recipients and 82% of placebo recipients (P=.114, by Fisher's exact test). Administration of echinacea before and after exposure to rhinovirus did not decrease the rate of infection; however, because of the small sample size, statistical hypothesis testing had relatively poor power to detect statistically significant differences in the frequency and severity of illness.

Adolescent↗
PubMed2000

The efficacy of echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: a randomized, double-blind placebo-controlled study.

OBJECTIVES: The aim of this study was to determine the efficacy of an echinacea compound herbal tea preparation (Echinacea Plus) given at early onset of cold or flu symptoms in a random assignment double-blind placebo-controlled study. DESIGN AND SUBJECTS: A total of 95 subjects with early symptoms of cold or flu (runny nose, scratchy throat, fever) were randomly assigned to receive Echinacea Plus tea five to six cups per day titrating to 1 over 5 days or placebo in a double-blind situation. Each participant completed a questionnaire 14 days after beginning the program. The efficacy, number of days the symptoms lasted, and number of days for change were measured with a self scoring questionnaire. RESULTS: The study period was 90 days (January 1, 1999 to March 30, 1999). There was a significant difference between the experimental group (Echinacea Plus) and control group (placebo) for all 3 questions measured: p < 0.001. There were no negative effects reported by any of the subjects in either group. CONCLUSIONS: Treatment with Echinacea Plus tea at early onset of cold or flu symptoms was effective for relieving these symptoms in a shorter period of time than a placebo.

Adult↗
PubMed2000

Evaluation of echinacea for treatment of the common cold.

Considered to have immunostimulating activity, echinacea is a widely used phytomedicinal for treatment of the common cold and upper respiratory tract infections (URTIs). We reviewed the literature from the MEDLINE database (January 1966-July 1999), International Pharmaceutical Abstracts (IPA) online database, Cambridge Scientific Abstracts Biological Sciences online database, Alt-Health Watch online database, EMBase CD-ROM database, and references from published articles, reviews, and letters to evaluate evidence from clinical trials of echinacea's purported efficacy for treating or preventing URTIs. Twelve clinical studies published from 1961-1997 concluded that echinacea was efficacious for treating the common cold, but the results are unclear due to inherent flaws in study design. Five trials were published since 1997; two showed that echinacea lacked efficacy for treating and preventing URTI symptoms, and three concluded that it was effective in reducing the frequency, duration, and severity of common cold symptoms. Again, these results are unclear because of methodologic uncertainties, such as small populations and use of noncommercially available, nonstandardized dosage forms. Although evidence for echinacea's efficacy is inconclusive, it appears to be safe. Patients without contraindications to it may not be dissuaded from using an appropriate preparation to treat the common cold.

Clinical Trials as Topic↗
PubMed2004

[Applied fundamental research of echinacea species].

Echinacea is a most famous "immune herb" in western countries, and continues to be the best selling herb for many years. For the last five years, our research group has cooperated with Institute of Medicinal Plants in Huairou District of Beijing, carrying out studies on Echinacea purpurea, which involved botany, cultivation, pharmacognosy, phytochemistry, quality control, pharmacology and toxicology of the species. Two other species introduced from Canada, Echinacea angustifolia and Echinacea pallida, were also included in the taxonomic, cultivated and pharmacognostic studies. The results acquired have opened up the path to introduce Echinacea species into Traditional Chinese Medicine, thus established the possibility of developing more promising drugs from them.

Animals↗
PubMed2006

The effect of Echinacea on upper respiratory infection symptom severity and quality of life.

We reviewed the current body of evidence supporting the use of Echinacea to reduce URI symptoms and improve QoL. Different Echinacea species have been administered either alone or in combination with other herbals and in various doses and dosage forms. Studies depicting Echinacea's effect on URI symptoms and QoL are contradictory. Despite some positive effects on symptom severity and QoL, given the current data available it would be inappropriate to attribute QoL benefit to Echinacea. The possibility that various facets of QoL may be improved with Echinacea cannot be ruled out. Further research into this compound is warranted.

Echinacea↗
PubMedDate not supplied

Echinacea root extracts for the prevention of upper respiratory tract infections: a double-blind, placebo-controlled randomized trial.

OBJECTIVE: To investigate the safety and efficacy of 2 extracts of echinacea for preventing upper respiratory tract infections. DESIGN: Three-armed, randomized, double-blind, placebo-controlled trial. SETTING: Four military institutions and 1 industrial plant. PARTICIPANTS: Three hundred two volunteers without acute illness at time of enrollment. INTERVENTIONS: Ethanolic extract from Echinacea purpurea roots, Echinacea angustifolia roots, or placebo, given orally for 12 weeks. MAIN OUTCOME MEASURE: Time until the first upper respiratory tract infection (time to event). Secondary outcome measures were the number of participants with at least 1 infection, global assessment, and adverse effects. RESULTS: The time until occurrence of the first upper respiratory tract infection was 66 days (95% confidence interval [CI], 61-72 days) in the E angustifolia group, 69 days (95% CI, 64-74 days) in the E purpurea group, and 65 days (95% CI, 59-70 days) in the placebo group (P = .49). In the placebo group, 36.7% had an infection. In the treatment groups, 32.0% in the E angustifolia group (relative risk compared with placebo, 0.87; 95% CI, 0.59-1.30) and 29.3% in the E purpurea group (relative risk compared with placebo, 0.80; 95% CI, 0.53-1.31) had an infection. Participants in the treatment groups believed that they had more benefit from the medication than those in the placebo group (P = .04). Adverse effects were reported by 18 subjects in the E angustifolia group, 10 in the E purpurea group, and 11 in the placebo group. CONCLUSION: In this study a prophylactic effect of the investigated echinacea extracts could not be shown. However, based on the results of this and 2 other studies, one could speculate that there might be an effect of echinacea products in the order of magnitude of 10% to 20% relative risk reduction. Future studies with much larger sample sizes would be needed to prove this effect.

Adult↗
PubMed2002

Echinacea stimulates macrophage function in the lung and spleen of normal rats.

Echinacea plant extract has been used for immunostimulation for many years but the evidence supporting its therapeutic potential is still controversial. Using male Sprague-Dawley rats (425-475 g), an in vivo study was conducted to examine the immunomodulatory effects of preparations of Echinacea containing its components cichoric acid, polysaccharides and alkylamides in different concentrations. The rats were gavaged orally with these preparations, two times/day for 4 days. Phagocytic activity of alveolar macrophage was increased with increasing concentrations of the Echinacea components. A trend of increase in TNF-alpha and nitric oxide release by the alveolar macrophages following an in vitro stimulation with LPS was also evident. An enhanced release of cytokines (such as TNF-alpha and IFN-gamma) in response to Echinacea components, was also apparent in rat's spleen macrophage, but at higher concentrations. These results suggest that the Echinacea preparations containing optimal concentrations of cichoric acid, polysaccharides and alkylamides are potentially effective in stimulating an in vivo, non-specific immune response in normal rats.

Journal Article↗
PubMed1999

Echinacea for upper respiratory infection.

OBJECTIVES: To review the evidence regarding the effectiveness of orally ingested Echinacea extracts in reducing the incidence, severity, or duration of acute upper respiratory infections (URIs). SEARCH STRATEGIES: Information from a wide range of sources was used as background material. More than 100 articles, books, and book chapters were reviewed for content and further references. Database searches, bibliographic reviews, and conversations with experts were carried out iteratively from January 1997 to February 1999. SELECTION CRITERIA: Published or unpublished reports of all blinded placebo-controlled randomized trials of any Echinacea formulation used as a treatment or for the prevention of URIs. DATA COLLECTION AND ANALYSIS: Review considerations included randomization, blinding, power, validity and clinical relevance of outcome measurements, inclusion and exclusion criteria, indistinguishability of treatment and placebo, and appropriateness of conclusions for the data presented. MAIN RESULTS. Nine treatment trials and 4 prevention trials fitting the selection criteria were found. Eight of the treatment trials reported generally positive results, and 3 of the prevention trials reported marginal benefit. Methodologic quality of the majority of the trials was modest. CONCLUSIONS: Evidence from published trials suggests that Echinacea may be beneficial for the early treatment of acute URIs. The influence of publication bias on those results is unknown. Echinacea preparations vary widely in composition, and are often found in combination with other potentially active constituents, making specific dose recommendations problematic. There is very little evidence supporting the prolonged use of Echinacea for the prevention of URIs.

Acute Disease↗
PubMed2005

The effect of seed source, light during germination, and cold-moist stratification on seed germination in three species of Echinacea for organic production.

Organic production of one of the most popular botanical supplements, Echinacea, continues to expand in the U.S. Echinacea seeds typically show a high degree of dormancy that can be broken by ethephon or gibberelic acid (GA), but these methods are currently disallowed in organic production. In order to determine the efficacy of non-chemical seed treatments, we evaluated the effect of varying seed source and supplying light, with and without cold-moist stratification, on seed germination of the three most important medicinal species of Echinacea, E. angustifolia DC, E. purpurea (L) Moench, and E. pallida (Nutt.) Nutt. Treatments included cold-moist stratification under 24 h light, 24 h dark, and 16/8 h light/dark to break seed dormancy. We found that germination was greater in the E. purpurea and E. pallida seeds from a commercial organic seed source compared to a public germplasm source. When seeds were not cold-moist stratified, 16-24 h light increased germination in E. angustifolia only. Echinacea angustifolia, E. purpurea, and E. pallida seeds that were cold-moist stratified under 16-24 h of light for 4 wk had a significantly greater percentage and rate of germination compared to seeds germinated in the dark. Therefore, cold-moist stratification under light conditions is recommended as a method to break seed dormancy and increase germination rates in organic production of Echinacea.

Journal Article↗
PubMed1987

[Experimental studies on the action of extracts of herba recens Echinaceae purpureae on skin flaps].

In animal experiments the effects of Echinacin, a sap made from Herba recens Echinaceae purpureae, on the rate of necrosis of skin flaps were studied in comparison with NaCl and pentoxifylline. The fluoresceine test was used as an indicator of peripheral circulation. The noncirculated area of the skin flap was significantly smaller in Herba Echinaceae treated animals than in control animals (p less than 0.01). On the day of the operation the size of the noncirculated flap area was only 56.0%, whereas it was 77.8% in the NaCl group and 67.4% in the pentoxifylline group. Until the 5th postoperative day the ratios changed to 47.4% (Herba Echinaceae), 76.6% (NaCl) and 50.4% (pentoxifylline). While more than two thirds of the skin flap area were to become necrotic in the NaCl group, less than half of the skin flap was so in the Herba Echinaceae group. Thus Herba Echinaceae significantly decreased the rate of necrosis of skin flaps in animal experiments.

Animals↗