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PubMed2005

Cytochrome P450 enzyme-mediated degradation of Echinacea alkylamides in human liver microsomes.

Echinacea preparations are widely used herbal remedies for the prevention and treatment of colds. In this study we have investigated the metabolism by human liver microsomes of the alkylamide components from an Echinacea preparation as well as that of pure synthetic alkylamides. No significant degradation of alkylamides was evident in cytosolic fractions. Time- and NADPH-dependent degradation of alkylamides was observed in microsomal fractions suggesting they are metabolised by cytochrome P450 (P450) enzymes in human liver. There was a difference in the susceptibility of 2-ene and 2,4-diene pure synthetic alkylamides to microsomal degradation with (2E)-N-isobutylundeca-2-ene-8,10-diynamide (1) metabolised to only a tenth the extent of (2E,4E,8Z,10Z)-N-isobutyldodeca-2,4,8,10-tetraenamide (3) under identical incubation conditions. Markedly less degradation of 3 was evident in the mixture of alkylamides present in an ethanolic Echinacea extract, suggesting that metabolism by liver P450s was dependent both on their chemistry and the combination present in the incubation. Co-incubation of 1 with 3 at equimolar concentrations resulted in a significant decrease in the metabolism of 3 by liver microsomes. This inhibition by 1, which has a terminal alkyne moiety, was found to be time- and concentration-dependent, and due to a mechanism-based inactivation of the P450s. Alkylamide metabolites were detected and found to be the predicted epoxidation, hydroxylation and dealkylation products. These findings suggest that Echinacea may effect the P450-mediated metabolism of other concurrently ingested pharmaceuticals.

Amides↗
PubMed2004

Effect of Atropa belladonna and Echinacea angustifolia in homeopathic dilution on experimental peritonitis.

Atropa belladonna and Echinacea angustifolia have been used in homeopathy as modulators of inflammatory processes, in simple potency or 'accord of potencies', as recommended by homotoxicology. We evaluated their effects on leukocyte migration and macrophage activity induced by experimental peritonitis in vivo. Mice were injected (i.p.) with LPS (1.0mg/kg) and treated (0.3ml/10g/day, s.c.) with different commercial forms of these medicines. Echinacea angustifolia D4--a simple potency preparation--and Belladonna Homaccord, Belladonna Injeel, Belladonna Injeel Forte, Echinacea Injeel and Echinacea Injeel Forte--all in 'accord of potencies'--were tested. The association of A. belladonna and E. angustifolia in 'accord of potencies' produced an increase of polymorphonuclear cell migration (Kruskal-Wallis, P = 0.03) and a decrease of mononuclear cell percentages (Kruskal-Wallis, P < or = 0.04), when compared with control, mainly in preparations containing low potencies. The proportion of degenerate leukocytes was lower in the treated groups, compared to a control group (P < or = 0.05). The treated groups showed increased phagocytosis (P < or = 0.05), mainly in preparations containing high potencies. Our results suggest that A. belladonna and E. angustifolia, when prepared in 'accord of potencies', modulate peritoneal inflammatory reaction and have a cytoprotective action on leukocytes.

Animals↗
PubMed2002

Anti-inflammatory and cicatrizing activity of Echinacea pallida Nutt. root extract.

Among the different species belonging to the Echinacea family, largely used in traditional medicine, Echinacea pallida, Echinacea purpurea and Echinacea angustifolia were investigated. These different species, due to their difficult identification, were commonly confused in the past and probably used indifferently for the same therapeutic purposes. In fact, the three species have in common, some pharmacological activities, based on the presence of active compounds that act additively and synergistically. Nevertheless, the composition of each species has slight variation in the amount of each active component. In particular, echinacoside, a caffeoyl derivative, is present in E. pallida and only in traces in E. angustifolia. It seems to have protective effects on skin connective tissue and to enhance wound healing. The anti-inflammatory and wound healing activities of echinacoside, compared with the ones of the total root extract of E. pallida and E. angustifolia, were examined in rats, after topical application. The tissues of the treated animals were evaluated after 24, 48 and 72 h treatment and excised for histological observation at the end of the experiment. Results confirm the good anti-inflammatory and wound healing properties of E. pallida and of its constituent echinacoside, with respect to E. purpurea and control. This activity probably resides in the antihyaluronidase activity of echinacoside.

Animals↗
PubMed2000

Studies on the antioxidant activity of Echinacea root extract.

Methanol extracts of freeze-dried Echinacea (E. angustifolia, E. pallida, and E. purpurea) roots were examined for free radical scavenging capacities and antioxidant activities. Root extracts of E. angustifolia, E. pallida, and E. purpurea were capable of scavenging hydroxyl radical. Similar scavenging activities for each variety were found for both 1,1-diphenyl-2-picrylhydrazyl radical and ABTS radical. Meanwhile, antioxidant activities of all three varieties of Echinacea were found to delay the formation of conjugated diene hydroperoxide induced by the thermal decomposition of 2, 2'-azobis(2-amidinopropane) dihydrochloride and extend the lag phase of peroxidation of soybean liposomes. Echinacea root extracts suppressed the oxidation of human low-density lipoprotein, as evaluated by reduced agarose electrophoretic mobility following oxidative modification by Cu(2+). The mechanisms of antioxidant activity of extracts derived from Echinacea roots included free radical scavenging and transition metal chelating.

Antioxidants↗
PubMed2003

Echinacea powder: treatment for canine chronic and seasonal upper respiratory tract infections.

An open multi-centered veterinary clinical trial, comparing conditions before and after treatment with a herbal preparation, containing the powdered root of Echinacea purpurea, was conducted by 6 practicing veterinarians in Switzerland. The plant-based immune stimulant was administered to 41 dogs with manifestations of chronic and seasonal upper respiratory tract infections, including pharyngitis/tonsillitis, bronchitis and kennel cough. Each animal was at an individual stage of the disease, with various symptoms and different severity scores, at start of treatment. There was no control group. Echinacea powder (1:3) was administered with the food at a dose of 1.0 g/10 kg body weight once daily for 8 weeks. Overall efficacy showed significant improvement for 92% of 39 dogs after 4 weeks of treatment and this was confirmed after 8 weeks. Significant reductions of severity and resolution of typical clinical symptoms, of clear nasal secretions, enlargement of lymph nodes, dry cough, dyspnea and dry lung sounds, were evident after 4 weeks. Only two adverse effects, not suspected to be attributable to the study drug, were recorded. Because quality and stability of the Echinacea powder were defined, using an analytical standard and purity tests, these data suggest, that the Echinacea preparation can be recommended as a well tolerated alternative treatment of canine upper respiratory tract infections.

Animals↗
PubMed2001

Recurrent erythema nodosum associated with Echinacea herbal therapy.

We report a case of recurrent erythema nodosum that is temporally and perhaps causally associated with use of echinacea herbal therapy. The genus Echinacea is traditionally used as an immunostimulant in the prophylaxis and treatment of upper respiratory tract infections. In vitro and in vivo studies of echinacea administration in animal and human-derived models suggest a definite stimulatory effect on the cellular immune system, although the clinical impact of echinacea is still unknown. The public's increasing use of alternative and complementary therapies necessitates that dermatologists be familiar with the cutaneous adverse effects of these agents.

Adult↗
PubMed2005

Treatment of the common cold with echinacea: a structured review.

BACKGROUND: Echinacea is a herbal preparation that is frequently used to treat the common cold. Spending on echinacea in the United States has risen to >300 million dollars annually. METHODS: A total of 322 articles related to echinacea and colds, including 9 placebo-controlled clinical trials, were identified using the Medline and PubMed databases. Eleven features of experimental design that affect the accuracy of the measurement of features of interest, the probability of a chance relationship, bias, and blinding were used to evaluate the 9 placebo-controlled studies. The criteria were validated case definition, quantifiable hypothesis, sample-size calculation, randomized assignment, double blinding, proof of blinding, measurement of compliance, measurement of drop-out rate, analysis by intention to treat, description of the methods of analysis, and measurement of probability. Equal weight was given to each criterion, since failure to meet any one of them could potentially invalidate the findings of a clinical trial. RESULTS: Of the 9 studies, 2 met all 11 criteria. The results of both studies were judged to be negative by the people who performed the studies. Of the remaining 7 studies, 6 were judged to have positive results, and 1 was judged to have negative results. The criterion most commonly not met was proof of blinding. CONCLUSIONS: This structured review suggests that the possible therapeutic effectiveness of echinacea in the treatment of colds has not been established.

Common Cold↗
PubMed2005

Echinacea intake induces an immune response through altered expression of leucocyte hsp70, increased white cell counts and improved erythrocyte antioxidant defences.

OBJECTIVE: To study the effect of Echinacea tablets on the expression of leucocyte heat shock protein 70 (hsp70), erythrocyte haemolysis, plasma antioxidant status, serum chemistry, haematological values and plasma alkylamide concentrations. METHOD: Eleven healthy individuals (26-61 years of age) were evaluated at baseline (day 1) and on day 15 after consuming two commercially blended Echinacea tablets daily for 14 days. RESULTS: Echinacea supplementation enhanced the fold increase in leucocyte hsp70 expression after a mild heat shock (P=0.029). White cell counts (WCC) were also increased (P=0.043). We also observed a preventative effect against free radical induced erythrocyte haemolysis (P=0.006) indicative of an antioxidant effect. CONCLUSION: The pilot study suggests that Echinacea may invoke an immune response through altered expression of hsp70 and increased WCC.

Administration, Oral↗
PubMed2003

Immune system effects of echinacea, ginseng, and astragalus: a review.

Traditional herbal medicine provides several remedies for strengthening the body's resistance to illness through effects on immune system components. This review article examines 3 popular herbal immune stimulants that are often of interest to cancer patients. Echinacea, a native of North America, is widely used to prevent, or provide early treatment for, colds. Preclinical studies lend biological plausibility to the idea that echinacea works through immune mechanisms. Numerous clinical trials have been carried out on echinacea preparations: it appears that the extracts shorten the duration and severity of colds and other upper respiratory infections (URIs) when given as soon as symptoms become evident. However, trials of long-term use of echinacea as a preventive have not shown positive results. Ginseng has been studied in some depth as an antifatigue agent, but studies of immune mechanisms have not proceeded so far. Preclinical evidence shows some immune-stimulating activity. There have been several clinical trials in a variety of different diseases. Astragalus is the least-studied agent. There are some preclinical trials that show intriguing immune activity. The herbs discussed appear to have satisfactory safety profiles. Cancer patients may wish to use these botanicals to inhibit tumor growth or to boost resistance to infections. However, passive immunotherapy with herbs, with no mechanism to expose tumor antigens, is unlikely to be effective in inhibiting tumor growth. Although the margin of safety for these herbs is large, more research is needed to demonstrate the clear value of using herbs to improve resistance to infections.

Adjuvants, Immunologic↗
PubMed2000

Immunopharmacological activity of Echinacea preparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells.

We have investigated the immunostimulatory, anti-inflammatory, and antioxidant activities of various Echinacea raw materials and commercially available products on murine macrophages and human peripheral blood mononuclear cells (PBMCs). To emulate oral dosing, a simulated digestion protocol was employed as a means of sample preparation. Echinacea-induced macrophage activation was used as a measure of immunostimulatory activity determined via quantitative assays for macrophage-derived factors including tumor necrosis factor alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, and nitric oxide. Echinacea herb and root powders were found to stimulate murine macrophage cytokine secretion as well as to significantly enhance the viability and/or proliferation of human PBMCs in vitro. In contrast, Echinacea extracts chemically standardized to phenolic acid or echinacoside content and fresh pressed juice preparations were found to be inactive as immunostimulatory agents but did display, to varying degrees, anti-inflammatory and antioxidant properties.

Adjuvants, Immunologic↗
PubMed2001

Can herbal products be used safely during pregnancy? Focus on echinacea.

QUESTION: Many of my patients are now using herbal medicines; some even use them during pregnancy. As we enter the "cold and flu" season, many are inquiring about use of the herb echinacea to prevent these ailments. Is there any evidence to suggest that use of echinacea during pregnancy is safe? ANSWER: Although herbal products have been used in the past during pregnancy and delivery, there is little evidence showing they are safe. Many authoritative reviews of echinacea report that its safety for use during pregnancy has not been established. A recent Motherisk study showed that use of echinacea during the first trimester of pregnancy was not associated with increased risk of major malformations.

Adult↗
PubMed2001

[Qualitative characteristics of selected species of the genus Echinacea Moench].

The paper examined the effect of production-technological conditions in relation to the ontogenetic stage of plants in three different species of the genus Echinacea Moench., comparing the species Echinacea purpurea, Echinacea atrorubens, and Echinacea pallida. It also examined the differences in the content of essential oil in different plant organs and evaluated the representation of individual components in the essential oils of the species under study at the stage of the optimal maturity for collection.

Chromatography, Gas↗
PubMed2003

Echinacea purpurea stimulates cellular immunity and anti-bacterial defence independently of the strain of mice.

One of the major functions of the immune system is anti-bacterial defence mediated among others by non-specific immunity (macrophages, granulocytes). Echinacea purpurea extracts are widely used in prophylaxis and therapy of various infections, mainly the respiratory tract, in animals and humans. The aim of this work was to evaluate the effect of prophylactic use of Echinacea purpurea extract on the development of Pseudomonas aeruginosa infection in various strains of mice and on some parameters of non-specific and also specific cellular immunity. Mice expressed various, depending on the strain used, susceptibility to infection. Echinacea feeding resulted in diminishing of bacteria number in livers of C57Bl/6 (susceptible strain) as well as B6C3F1 (relative resistant strain) mice. Echinacea feeding of the second relative resistant strain (BALB/c x C3H) F1 resulted in stimulation of granulocytes chemiluminescent and lymphocytes proliferative response.

Adjuvants, Immunologic↗
PubMed2004

The effect of Echinacea purpurea extract on sexual glands of male rats.

UNLABELLED: Fifty percent of men over the age of fifty are diagnosed benign prostate hyperplasia. It is caused by disorders in the balance of androgens and estrogens, depending on the activity of sexual glands; therefore it is advisable to examine the functioning of these organs and to determine the pathogenetic mechanism of effect of this pathology. The antiandrogenic effect of Echinacea preparations was examined in our previous study and hypoplasia of histological structures and the mass reduction of prostate were determined. This encouraged more detailed investigation of the effect of the preparation directly to the organs, participating in the synthesis of the male hormone - testosterone. The effect of Echinacea extract on a testicle and epididymis was examined, the mass of these organs was determined, the proportion between the mass of the organ and the mass of a body was calculated, the changes in histological structures were evaluated in this study. MATERIAL AND METHODS: Experiments with the Wistar line 3-month-old male rats were carried out. There were three experimental groups of rats. The first one was control group. The rats of the second group were fed on the usual food enriched with the Echinacea extract additive with the proportion of 50 mg/kg for 4 weeks. The rats in the third group were fed equally to the second one for 8 weeks. The clinical death of the animals was caused by overdosage of the solution of phenobarbital (1 mg/kg). The rats were weighed, the testicles and epididymis were eliminated, and pathohistological examinations were carried out. RESULTS: The average weight of the male rats in the control group was 1530+/-166.37mg, in the second group - 1520+/-164.62mg, and in the third group -1499+/-158.81 mg. Calculations of the relative quantity between the mass of the organs and the body weight were made and it was estimated that the testicles of the rats in the first group made up 0.496+/-0.399% of a body mass, in the second one -0.459+/-0.419%, and in the third one - 0.429+/-0.410%. The epididymis in the control group made up 0.189+/-0.332% of a body mass; in the second one - 0.1733+/-0.328%, and in the third one - 0.1723+/-0.198%. The histological structural changes were traced after 4 weeks of using the preparation, however they became more obvious after 8 weeks. CONCLUSION: Results of the study enabled to determine statistically significant reduction in the percentage of a testicle and the body mass, as well as changes in histological structures after 8 weeks of consuming extract of Echinacea purpurea.

Androgen Antagonists↗
PubMed1996

Cytokine production in leukocyte cultures during therapy with Echinacea extract.

We measured the levels of the cytokines IL-1-alpha, IL-1-beta, IL-2, IL-6, TNF-alpha, and IFN-gamma in culture supernatants of stimulated whole blood cells derived from 23 tumor patients undergoing a 4-week oral treatment with a spagyric extract from Echinacea angustifolia, Eupatorium perfoliatum, and Thuja occidentalis (Echinacea complex). All patients had had curative surgery for a localized solid malignant tumor. Blood was taken before treatment and after 2 and 4 weeks of therapy. Twelve untreated tumor patients at the same clinical stage, also after curative surgery, served as a control group. In the blood cell cultures of all patients, a rather wide range of cytokine levels was found. After therapy with Echinacea complex, no significant alteration in the production of the cytokines could be seen in comparison to the controls, and also the leukocyte populations remained constant. We conclude that at this application and dosage, the therapy with Echinacea complex has no detectable effect on tumor patients' lymphocytes activity as measured by their cytokine production.

Administration, Oral↗
PubMed1999

Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis.

A number of immunomodulatory effects have been attributed to the medicinal plants Echinacea angustifolia and Goldenseal (Hydrastis canadensis); however, little is known about whether treatment with these plants can enhance antigen-specific immunity. We investigated the antigen-specific in vivo immunomodulatory potential of continuous treatment with Echinacea and Goldenseal root extract over a period of 6 weeks using rats that were injected with the novel antigen keyhole limpet hemocyanin (KLH) and re-exposed to KLH after the initial exposure. Immunoglobulin production was monitored via ELISA continuously over a period of 6 weeks. The Echinacea-treated group showed a significant augmentation of their primary and secondary IgG response to the antigen, whereas the Goldenseal-treated group showed an increase in the primary IgM response during the first 2 weeks of treatment. Our results suggest that medicinal plants like Echinacea or Goldenseal may enhance immune function by increasing antigen-specific immunoglobulin production.

Adjuvants, Immunologic↗
PubMed1998

Echinacea-associated anaphylaxis.

A woman with atopy experienced anaphylaxis after taking, among other dietary supplements, a commercial extract of echinacea. Hypersensitivity was confirmed by skinprick and RAST testing. Regular ingestion of echinacea by up to 5% of surveyed patients with atopy, combined with detection of echinacea-binding IgE in atopic subjects (19% by skin testing; 20% with moderate to strong reactivity by RAST testing), raises the possibility of severe allergic reactions, even with first-time use, due to cross-reactivity with other structurally similar allergens. Patients with atopy should be cautioned about the risk of developing life-threatening reactions to complementary medicines, including echinacea.

Adult↗
PubMed2004

Effectiveness of an herbal preparation containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study.

OBJECTIVE: To evaluate the effectiveness and safety of a preparation containing echinacea, propolis, and vitamin C in the prevention of respiratory tract infections in children during a 12-week winter period. DESIGN: Randomized, double-blind, placebo-controlled study. SUBJECTS: Four hundred thirty children, aged 1 to 5 years, were randomized to an herbal extract preparation (n = 215) or a placebo elixir (n = 215). INTERVENTION: Administration of an herbal preparation (Chizukit) containing 50 mg/mL of echinacea, 50 mg/mL of propolis, and 10 mg/mL of vitamin C, or placebo (5.0 mL and 7.5 mL twice daily for ages 1 to 3 years and 4 to 5 years, respectively) for 12 weeks. RESULTS: Significant mean +/- SD reductions of illnesses were seen in the Chizukit group in the number of illness episodes, 138 vs 308 (55% reduction); number of episodes per child, 0.9 +/- 1.1 vs 1.8 +/- 1.3 (50% reduction, P<.001); and number of days with fever per child, 2.1 +/- 2.9 vs 5.4 +/- 4.4) (62% reduction, P<.001). The total number of illness days and duration of individual episodes were also significantly lower in the Chizukit group. Adverse drug reactions were rare, mild, and transient. CONCLUSION: A preventive effect of a product containing echinacea, propolis, and vitamin C on the incidence of respiratory tract infections was observed.

Ascorbic Acid↗