Echinacea Preparations Research Articles

Echinacea Reduces Antibiotics by Preventing Respiratory Infections: A Meta-Analysis (ERA-PRIMA).

Respiratory tract infections (RTIs) are the leading cause of antibiotic prescriptions, primarily due to the risk for secondary bacterial infections. In this study, we examined whether Echinacea could reduce the need for antibiotics by preventing RTIs and their complications, and subsequently investigated its safety profile. A comprehensive search of EMBASE, PubMed, Google Scholar, Cochrane DARE and clinicaltrials.gov identified 30 clinical trials (39 comparisons) studying Echinacea for the prevention or treatment of RTIs in 5652 subjects. Echinacea significantly reduced the monthly RTI occurrence, risk ratio (RR) 0.68 (95% CI 0.61-0.77) and number of patients with ≥1 RTI, RR = 0.75 [95% CI 0.69-0.81] corresponding to an odds ratio 0.53 [95% CI 0.42-0.67]. Echinacea reduced the risk of recurrent infections (RR = 0.60; 95% CI 0.46-0.80), RTI complications (RR = 0.44; 95% CI 0.36-0.54) and the need for antibiotic therapy (RR = 0.60; 95% CI 0.39-0.93), with total antibiotic therapy days reduced by 70% (IRR = 0.29; 95% CI 0.11-0.74). Alcoholic extracts from freshly harvested Echinacea purpurea were the strongest, with an 80% reduction of antibiotic treatment days, IRR 0.21 [95% CI 0.15-0.28]. An equal number of adverse events occurred with Echinacea and control treatment. Echinacea can safely prevent RTIs and associated complications, thereby decreasing the demand for antibiotics. Relevant differences exist between Echinacea preparations.

A standardized extract of Echinacea purpurea containing higher chicoric acid content enhances immune function in murine macrophages and cyclophosphamide-induced immunosuppression mice

Context Preparations of Echinacea have been used by herbalists to boost the immune system. Objective In this study, Echinacea purpurea (L.) Moench (Asteraceae) extract with enriched chicoric acid content was investigated for immunomodulation. Materials and methods The standardized hydroalcoholic extract (4% chicoric acid) was prepared from the aerial parts of E. purpurea (SEP). The extract was screened for in vitro antioxidant activities, and immunomodulation in RAW 264.7 cells, at 200 and 400 µg/mL. Further, the male BALB/c mice (20-25 g) were divided into 4 groups (n = 6 per group). All the groups except control, were intraperitoneally injected with 70 mg/kg/day of cyclophosphamide (CTX) for 4 consecutive days. The treatment groups received SEP extract (100 and 200 mg/kg body weight) p.o. from day 5 to 14. Results The SEP extract inhibited DPPH (IC50 = 106.7 µg/mL), ABTS+ (IC50 = 19.88 µg/mL) and nitric oxide (IC50 = 120.1 µg/mL). The SEP extract’s ORAC (oxygen radical absorbance capacity) value was 1931.63 µM TE/g. In RAW 264.7 cells, SEP extract increased the nitric oxide production by 30.76- and 39.07-fold at 200 and 400 µg/mL, respectively, compared to the untreated cells. SEP extract significantly increased phagocytosis and cytokine release (TNF-α, IL-6, and IL-1β) in the cells. Further, the extract improved immune organ indices, lymphocyte proliferation and serum cytokine levels in CTX-induced mice. The extract at 200 mg/kg significantly increased the natural killer cell activity (24.6%) and phagocytic index (28.03%) of CTX mice. Conclusion Our results strongly support SEP extract with 4% chicoric acid as a functional ingredient for immunomodulation.

Study of phenol carboxylic acids in echinacea grass and echinacea tablets in order to develop a technique for their quantitative determination using high-performance liquid chromatography (HPLC)

Echinacea herb and preparations based on it have the immunomodulatory and anti-inflammatory properties necessary for today, which is due to the presence of phenolcarboxylic acids in their composition. At the moment, the quantitative determination of phenolcarboxylic acids in echinacea tablets requires time-consuming sample preparation and determination by a spectrophotometric method that does not have sufficient specificity. In this regard, it is proposed to standardize the quantitative determination of phenolcarboxylic acids in echinacea tablets by HPLC, which will effectively separate the components of the mixture to study its composition, establish the dominant of chicory acid in the water-ethanol extract, and also reduce the time spent on analysis.

Echinacea in hepatopathy: A review of its phytochemistry, pharmacology, and safety

BackgroundEchinacea, one of the most popular herbs with double function of immunity and anti-inflammatory activity, has now attracted much interest for a possible alternative for the treatment of hepatopathy. This review is aimed at providing a comprehensive overview of Echinacea regarding its chemical composition, pharmacological action against various hepatopathy, and safety. MethodsA comprehensive search of published articles was conducted to focus on original publications related to Echinacea and hepatopathy till the end of 2020 using various literature databases, including China National Knowledge Infrastructure, PubMed, and Web of Science database. ResultsEchinacea exhibited excellent activities in resisting a variety of hepatopathy induced by different causes in preclinical experiments and clinical trials by regulating cell proliferation and apoptosis, antioxidant defense mechanism, voltage-gated sodium channels, lipid metabolism, circadian rhythm, p38 MAPK signaling pathway, JNK signaling pathway, Nrf2/HO-1 signaling pathway, PI3K/AKT signaling pathway, and Akt/GSK3 beta signaling pathways. The high efficacy of Echinacea is related to its immunomodulatory and anti-inflammatory activities. The main ingredients of Echinacea include caffeic acid derivatives, alkylamides, and polysaccharides, which have been well established in preclinical studies of liver diseases. Studies on acute and subacute toxicity show that Echinacea preparations are well-tolerated herbal medicines. ConclusionEchinacea may offer a novel potential strategy for clinical prevention and treatment of liver diseases and related diseases. Extensive studies are necessary to identify the underlying mechanisms and establish future therapeutic potentials of this herb. Well-designed clinical trials are still warranted to confirm the safety and effectiveness of Echinacea for hepatopathy.

Prevention of Infections of the Upper Respiratory Tract

Because of its high prevalence acute respiratory diseases have a significant impact on the population. The focus of this review was the current state of knowledge for the prophylactic efficacy of: zinc, vitamin C, Echinacea preparations, garlic and carrying out physical measures. Furthermore, the benefits of pneumococcal and influenza vaccine were elicited. In the synopsis, the physical measures proved to be the most effective, cost-effective method to prevent infections. The intake of zinc, Echinacea preparations (for example: E. purpurea), vitamin C and garlic showed moderate success in the prevention of infection and must be elicited individually. Pneumococcal and annual influenza vaccines in family practice should be given furthermore accordingly topical STIKO-recommendation. Nevertheless, the prophylactic effect from influenza vaccines on usual cold illnesses is unsettled.

Prevention of Infections of the Upper Respiratory Tract

Because of its high prevalence acute respiratory diseases have a significant impact on the population. The focus of this review was the current state of knowledge for the prophylactic efficacy of: zinc, vitamin C, Echinacea preparations, garlic and carrying out physical measures. Furthermore, the benefits of pneumococcal and influenza vaccine were elicited. In the synopsis, the physical measures proved to be the most effective, cost-effective method to prevent infections. The intake of zinc, Echinacea preparations (for example: E. purpurea), vitamin C and garlic showed moderate success in the prevention of infection and must be elicited individually. Pneumococcal and annual influenza vaccines in family practice should be given furthermore accordingly topical STIKO-recommendation. Nevertheless, the prophylactic effect from influenza vaccines on usual cold illnesses is unsettled.

ARGUMENTATION OF ACUTE RESPIRATORY VIRAL INFECTIONS NONSPECIFIC PREVENTION IN GROUPS OF CHILDREN

Acute respiratory viral infections (ARVI) and influenza are among the topical problems of healthcare. The children’s morbidity index in preschool educational institutions in Krasnoselsky district of St. Petersburg in 2008–2014 varied from 1359.6 to 1768.5 per 1000 children attending these institutions. In general educational schools the morbidity index in the aforesaid period were 422.6–521.6 (p 0.001). From 49.3 to 55.4% of children were vaccinated against influenza; from 3600 to 4700 children annually stayed unimmunized due to medical contraindications and parents’ refusals from prophylactic immunization. The research objective is clinical-epidemiological substantiation of effectiveness of application of Echinacea botanical medicine to reduce the ARVI morbidity and the rate of complications after the disease among children attending educational institutions. As a result of the research it was established that the ARVI morbidity index in the group of the children who received the Echinacea preparation was 76.8; in the comparison group it was 94.2 per 100 people (p 0.01; RR = 0.80; CI = 0.7–0.9). The rate of complications (bronchitis, otitis, adenoiditis, pneumonia, sinusitis) among the children who received the preparation was 2–4.8 times lower.

Assessing the Effect of Orally Administered <I>Echinacea purpurea</I> Extracts vs. Placebo on Pro-Inflammatory Cytokine Responses <I>Ex Vivo</I>

Objective: To determine if aqueous, polysaccharide-containing Echinacea purpurea extracts taken orally increase pro-inflammatory cytokine responses ex vivo. Design: In two separate studies, the levels of TNF-alpha (TNF), interleukins 2 and 6 (IL-2 and IL-6) and interferon gamma (IFN-γ) secreted by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from healthy adults randomized to take one of three E. purpurea formulations or placebo orally for 10 consecutive days were measured. Blood was obtained from participants at baseline and on days 2, 3, 7, and 10 while on study medication. PBMC were isolated and stimulated with PHA for 24 h, and supernatants collected for measurement of pro-inflammatory cytokine levels.Outcome Measures: Primary outcomes were peak concentrations of PHA-induced TNF, IL-2, IL-6, and IFN-γ from PBMC isolates collected while on study medication. Cytokine responses of PBMC from participants randomized to one of the Echinacea formulations were compared with those of placebo recipients by regression analysis.Results: Cytokine levels were obtained from mitogen-activated PBMC from 86 participants, collected while on study medication. No significant differences in the peak levels of PBMC-secreted TNF, IL-2, IL-6 and IFN-γ were observed between PBMC from those taking active Echinacea preparation vs. a placebo. After adjusting for age, a trend toward increased IL-6 secreted by PHA-stimulated PBMC isolated on day 3 of oral administration was observed for the group taking one of the E. purpurea formulations compared with placebo (P=0.064).Conclusions: Oral administration of E. purpurea did not significantly enhance peak pro-inflammatory cytokine responses in mitogen-stimulated PBMC.

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

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

Echinacea complex – chemical view and anti-asthmatic profile

Ethnopharmacological relevanceEchinacea purpurea (L.) Moench is one of the mostly used herbs in the traditional medicine for the treatment of respiratory diseases. Modern interest in Echinacea is directed to its immunomodulatory activity. Recent studies have shown that secretion of asthma-related cytokines in the bronchial epithelial cells can be reversed by Echinacea preparations. Aim of the studyTo examine the pharmacodynamics profile of Echinacea active principles, a complex has been isolated from its flowers by alkaline extraction and has been tested using an animal model of allergic asthma. Material and methodsThe structural features of Echinacea purpurea complex was determined using chemical and spectroscopic methods. Allergic inflammation of the airways was induced by repetitive exposure of guinea pigs to ovalbumin. Echinacea complex was then administered 14 days in 50mg/kg b.w. daily dose perorally. Bronchodilatory effect was verified as decrease in the specific airway resistance (sRaw) in vivo and by reduced contraction amplitude (mN) of tracheal and pulmonary smooth muscle to cumulative concentrations of acetylcholine and histamine in vitro. The impact on mucociliary clearance evaluated measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software. Anti-inflammatory effect of Echinacea complex was verified by changes in exhaled NO levels and by Bio-Plex® assay of Th2 cytokine concentrations (IL-4, IL-5, IL-13 and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF). ResultsChemical and spectroscopic studies confirmed the presence of carbohydrates, phenolic compounds and proteins, as well as the dominance of rhamnogalacturonan and arabinogalactan moieties in Echinacea complex. The significant decrease in sRaw values and suppressed histamine and acetylcholine-induced contractile amplitude of isolated airways smooth muscle that were similar to effects of control drug salbutamol confirmed Echinacea complex bronchodilatory activity. The anti-inflammatory effect was comparable with that of control agent budesonide and was verified as significantly reduced exhaled NO levels and concentration of Th2 cytokines in serum and BALF. The values of CBF were changed only insignificantly on long-term administration of Echinacea complex suggested its minimal negative impact on mucociliary clearance. ConclusionPharmacodynamic studies have confirmed significant bronchodilatory and anti-inflammatory effects of Echinacea complex that was similar to effects of classic synthetic drugs. Thus, results provide a scientific basis for the application of this herb in traditional medicine as a supplementary treatment of allergic disorders of the airways, such as asthma.

Ethanolic Echinacea purpurea Extracts Contain a Mixture of Cytokine-Suppressive and Cytokine-Inducing Compounds, Including Some That Originate from Endophytic Bacteria.

Echinacea preparations, which are used for the prevention and treatment of upper respiratory infections, account for 10% of the dietary supplement market in the U.S., with sales totaling more than $100 million annually. In an attempt to shed light on Echinacea's mechanism of action, we evaluated the effects of a 75% ethanolic root extract of Echinacea purpurea, prepared in accord with industry methods, on cytokine and chemokine production from RAW 264.7 macrophage-like cells. We found that the extract displayed dual activities; the extract could itself stimulate production of the cytokine TNF-α, and also suppress production of TNF-α in response to stimulation with exogenous LPS. Liquid:liquid partitioning followed by normal-phase flash chromatography resulted in separation of the stimulatory and inhibitory activities into different fractions, confirming the complex nature of this extract. We also studied the role of alkylamides in the suppressive activity of this E. purpurea extract. Our fractionation method concentrated the alkylamides into a single fraction, which suppressed production of TNF-α, CCL3, and CCL5; however fractions that did not contain detectable alkylamides also displayed similar suppressive effects. Alkylamides, therefore, likely contribute to the suppressive activity of the extract but are not solely responsible for that activity. From the fractions without detectable alkylamides, we purified xanthienopyran, a compound not previously known to be a constituent of the Echinacea genus. Xanthienopyran suppressed production of TNF-α suggesting that it may contribute to the suppressive activity of the crude ethanolic extract. Finally, we show that ethanolic extracts prepared from E. purpurea plants grown under sterile conditions and from sterilized seeds, do not contain LPS and do not stimulate macrophage production of TNF-α, supporting the hypothesis that the macrophage-stimulating activity in E. purpurea extracts can originate from endophytic bacteria. Together, our findings indicate that ethanolic E. purpurea extracts contain multiple constituents that differentially regulate cytokine production by macrophages.

Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway

1. This study investigated the mechanism underlying Echinacea-mediated induction of CYP1A2, CYP3A4 and MDR1 in terms of human pregnane X receptor (PXR) activation.2. Crude extracts and fractions of Echinacea purpurea were tested for PXR activation in HepG2 cells by a reporter gene assay. Quantitative real-time PCR was carried out to determine their effects on CYP1A2 and CYP3A4 mRNA expressions. Capsules and fractions were risk ranked as high, intermediate and remote risk of drug-metabolizing enzymes induction based on EC50 values determined for respective CYPs.3. Fractions F1, F2 and capsule (2660) strongly activated PXR with 5-, 4- and 3.5-fold increase in activity, respectively. Echinacea preparations potentiated up-regulation of CYP1A2, CYP3A4 and MDR1 via PXR activation.4. Thus E. purpurea preparations cause herb–drug interaction by up-regulating CYP1A2, CYP3A4 and P-gp via PXR activation.

Echinacea and elderberry—should they be used against upper respiratory tract infections during pregnancy?

This review evaluates the safety of echinacea and elderberry in pregnancy. Both herbs are commonly used to prevent or treat upper respiratory tract infections (URTIs) and surveys have shown that they are also used by pregnant women. The electronic databases PubMed, ISI Web of Science, AMED, EMBASE, Natural Medicines Comprehensive Database, and Cochrane Library were searched from inception to November 2013. Relevant references from the acquired articles were included. No clinical trials concerning safety of either herb in pregnancy were identified. One prospective human study and two small animal studies of safety of echinacea in pregnancy were identified. No animal- or human studies of safety of elderberry in pregnancy were identified. Twenty clinical trials concerning efficacy of various echinacea preparations in various groups of the population were identified between 1995 and 2013. Three clinical trials concerning efficacy of two different elderberry preparations were identified between 1995 and 2013. The results from the human and animal studies of Echinacea sp. are not sufficient to conclude on the safety in pregnancy. The prospective, controlled study in humans found no increase in risk of major malformations. The efficacy of Echinacea sp. is dubious based on the identified studies. Over 2000 persons were given the treatment, but equal amounts of studies of good quality found positive and negative results. All three clinical trials of Elderberry concluded that it is effective against influenza, but only 77 persons were given the treatment. Due to lack of evidence of efficacy and safety, health care personnel should not advice pregnant women to use echinacea or elderberry against upper respiratory tract infection.

Echinacea for preventing and treating the common cold.

Echinacea plant preparations (family Asteraceae) are widely used in Europe and North America for common colds. Most consumers and physicians are not aware that products available under the term Echinacea differ appreciably in their composition, mainly due to the use of variable plant material, extraction methods and the addition of other components. To assess whether there is evidence that Echinacea preparations are effective and safe compared to placebo in the prevention and treatment of the common cold. We searched CENTRAL 2013, Issue 5, MEDLINE (1946 to May week 5, 2013), EMBASE (1991 to June 2013), CINAHL (1981 to June 2013), AMED (1985 to February 2012), LILACS (1981 to June 2013), Web of Science (1955 to June 2013), CAMBASE (no time limits), the Centre for Complementary Medicine Research (1988 to September 2007), WHO ICTRP and clinicaltrials.gov (last searched 5 June 2013), screened references and asked experts in the field about published and unpublished studies. Randomized controlled trials (RCTs) comparing mono-preparations of Echinacea with placebo. At least two review authors independently assessed eligibility and trial quality and extracted data. The primary efficacy outcome was the number of individuals with at least one cold in prevention trials and the duration of colds in treatment trials. For all included trials the primary safety and acceptability outcome was the number of participants dropping out due to adverse events. We assessed trial quality using the Cochrane 'Risk of bias' tool. Twenty-four double-blind trials with 4631 participants including a total of 33 comparisons of Echinacea preparations and placebo met the inclusion criteria. A variety of different Echinacea preparations based on different species and parts of plant were used. Evidence from seven trials was available for preparations based on the aerial parts of Echinacea purpurea. Ten trials were considered to have a low risk of bias, six to have an unclear risk of bias and eight to have a high risk of bias. Ten trials with 13 comparisons investigated prevention and 15 trials with 20 comparisons investigated treatment of colds (one trial addressed both prevention and treatment).Due to the strong clinical heterogeneity of the studies we refrained from pooling for the main analysis. None of the 12 prevention comparisons reporting the number of patients with at least one cold episode found a statistically significant difference. However a post hoc pooling of their results, suggests a relative risk reduction of 10% to 20%. Of the seven treatment trials reporting data on the duration of colds, only one showed a significant effect of Echinacea over placebo. The number of patients dropping out or reporting adverse effects did not differ significantly between treatment and control groups in prevention and treatment trials. However, in prevention trials there was a trend towards a larger number of patients dropping out due to adverse events in the treatment groups. Echinacea products have not here been shown to provide benefits for treating colds, although, it is possible there is a weak benefit from some Echinacea products: the results of individual prophylaxis trials consistently show positive (if non-significant) trends, although potential effects are of questionable clinical relevance.

Quantification of Phenylpropanoids in Commercial Echinacea Products Using TLC with Video Densitometry as Detection Technique and ANN for Data Modelling

Echinacea preparations are among the most popular herbal remedies worldwide. Although it is generally assigned immune enhancement activities, the effectiveness of Echinacea is highly dependent on the Echinacea species, part of the plant used, the age of the plant, its location and the method of extraction. The aim of this study was to investigate the capacity of an artificial neural network (ANN) to analyse thin-layer chromatography (TLC) chromatograms as fingerprint patterns for quantitative estimation of three phenylpropanoid markers (chicoric acid, chlorogenic acid and echinacoside) in commercial Echinacea products. By applying samples with different weight ratios of marker compounds to the system, a database of chromatograms was constructed. One hundred and one signal intensities in each of the TLC chromatograms were correlated to the amounts of applied echinacoside, chlorogenic acid and chicoric acid using an ANN. The developed ANN correlation was used to quantify the amounts of three marker compounds in Echinacea commercial formulations. The minimum quantifiable level of 63, 154 and 98 ng and the limit of detection of 19, 46 and 29 ng were established for echinacoside, chlorogenic acid and chicoric acid respectively. A novel method for quality control of herbal products, based on TLC separation, high-resolution digital plate imaging and ANN data analysis has been developed. The method proposed can be adopted for routine evaluation of the phytochemical variability in Echinacea formulations available in the market.

Anti-Influenza Virus Activities of Commercial Oregano oils and their Carriers

Commercial Oregano oils with high concentrations of carvacrol have been vigorously promoted as antiviral agents effective against colds and ‘flu, including the pandemic H1N1 virus. However there seems to be no evidence to support these claims. Furthermore, since carvacrol itself is known to be toxic, so-called “carrier oils”, such as olive oil, have been included in formulations to ameliorate the potential toxic effects. We compared the antiinfluenza virus activity of several preparations, with and without “carriers”, and pure olive oil and carvacrol, by means of quantitative assays for H1N1 influenza virus, and for cytotoxicity in human lung epithelial cells. A range of concentrations was evaluated, including those relevant to consumer applications. All five Oregano oils showed significant antiviral activity, as did olive oil by itself, although their potencies were not comparable to a standardized preparation of Echinacea purpurea. Carvacrol was also very active, but it was also strongly cytotoxic. In addition all the Oregano oils were more cytotoxic than Echinacea purpurea. Thus certain commercial Oregano oils do possess anti-influenza virus activities, although these are less than a potent standardized Echinacea preparation, and furthermore the toxicity of the oils to lung epithelial cells, at doses relevant to consumer applications, is a limiting factor in their usefulness for oral applications.

Herb-Drug Interactions: Effects of Echinacea preparations on cytochrome P450 activities in rats

Herb-Drug Interactions: Effects of Echinacea preparations on cytochrome P450 activities in rats

Effect of Echinacea alone or in combination with silymarin in the carbon-tetrachloride model of hepatotoxicity

Echinacea preparations are widely used in the prevention or treatment of upper respiratory tract infections. The present study aimed to investigate the effect of a standardized Echinacea extract in experimentally induced liver toxicity and whether this herb would have a modulating effect on the silymarin-induced hepatoprotection in rats. Liver damage was induced by the administration of carbon tetrachloride (CCl4). Echinacea extract (18 or 36 mg/kg) alone or combined with silymarin (25 mg/kg), silymarin only (25 mg/kg), or saline (control) was given once daily orally simultaneously with CCl4 and for 1 week thereafter. Serum alanine aminotransferase (ALT) or aspartate aminotransferase were not significantly changed by treatment with Echinacea, but alkaline phosphatase (ALP) in serum decreased by 23.6% by the extract at 36 mg/kg. Silymarin given in combination with either dose of Echinacea resulted in 34.9% and 57.8% reduction in AST, 42.7% and 58% reduction in ALT and 41% and 60% reduction in ALP, compared with CCl4 control group. Silymarin alone reduced ALT, AST, and ALP levels by 58.8%, 61.2%, and 62.2%, respectively. Histopathological examination revealed a mild decrease in degenerated hepatocytes after treatment with 36 mg/kg of Echinacea. Noticeable improvement in the liver damage was observed upon the addition of silymarin to Echinacea. A marked decrease of intracellular protein and glycogen staining was evident after the administration of CCl4. Slight improvement in protein and glycogen staining was noted after 36 mg/kg of Echinacea. Increased hepatic protein and glycogen staining intensity was observed after silymarin and Echinacea co-treatment compared with Echinacea-only treated groups. Silymarin only treatment resulted in more or less normal histopathological and histochemical findings. The present results suggest that administration of Echinacea extract reduces the hepatoprotective effect of silymarin. Such finding is likely to have important clinical significance in patients with hepatic disease on silymarin treatment.

Effects of Echinaforce® treatment on ex vivo-stimulated blood cells

The herb Echinacea purpurea, also called purple coneflower, is regarded as an immune modulator. This study examined changes in cytokine production in blood samples from 30 volunteers before and during 8-day oral administration with an ethanolic extract of fresh Echinacea purpurea (Echinaforce(®)). Daily blood samples were ex vivo stimulated by LPS/SEB or Zymosan and analysed for a series of cytokines and haematological and metabolic parameters. Treatment reduced the proinflammatory mediators TNF-α and IL-1β by up to 24% (p<0.05) and increased anti-inflammatory IL-10 levels by 13% (p<0.05) in comparison to baseline. This demonstrated a substantial overall anti-inflammatory effect of Echinaforce(®) for the whole group (n=28). Chemokines MCP-1 and IL-8 were upregulated by 15% in samples from subjects treated with Echinaforce(®) (p<0.05). An analysis of a subgroup of volunteers who showed low pre-treatment levels of the cytokines MCP-1, IL-8, IL-10 or IFN-γ (n=8) showed significant stimulation of these factors upon Echinaforce(®) treatment (30-49% increases; p<0.05), whereas the levels in subjects with higher pre-treatment levels remained unaffected. We chose the term "adapted immune-modulation" to describe this observation. Volunteers who reported high stress levels (n=7) and more than 2 colds per year experienced a significant transient increase in IFN-γ upon Echinaforce(®) treatment (>50%). Subjects with low cortisol levels (n=11) showed significant down-regulation of the acute-phase proteins IL1-β, IL-6, IL-12 and TNF-α by Echinaforce(®) (range, 13-25%), while subjects with higher cortisol levels showed no such down-regulation. This is the first ex vivo study to demonstrate adapted immune-modulation by an Echinacea preparation. While Echinaforce(®) did not affect leukocyte counts, we speculate that the underlying therapeutic mechanism is based on differential multi-level modulation of the responses of the different types of leukocytes. Echinaforce(®) thus regulates the production of chemokines and cytokines according to current immune status, such as responsiveness to exogenous stimuli, susceptibility to viral infection and exposure to stress.

The Effects of an Echinacea Preparation on Synaptic Transmission and the Firing Properties of CA1 Pyramidal Cells in the Hippocampus

Traditionally, Echinacea preparations are used as antiinflammatory agents and immune-enhancers. In addition to these effects, their anxiolytic potency has been recognized recently in laboratory tests. Our aim in this study was to uncover the potential effects of an Echinacea preparation on neuronal operations in the hippocampus, a brain region that is involved in anxiety and anxiety-related behaviors. Using in vitro electrophysiological techniques, we observed that excitatory synaptic transmission in hippocampal slices was significantly suppressed by an Echinacea extract found to be effective in anxiety tests. In contrast, no change in inhibitory synaptic transmission could be detected upon application of this extract. In addition, our experiments revealed that at low concentration the Echinacea extract reduced the spiking activity of CA1 pyramidal cells, while at high concentration increased it. This latter observation was parallel to the reduction in the magnitude of the h-current-mediated voltage responses in pyramidal cells. At any concentrations, the passive membrane properties of CA1 pyramidal cells were found to be unaltered by the Echinacea extract. In summary, the Echinacea extract can significantly regulate excitatory, but not inhibitory, synaptic transmission in the hippocampus, and this action might be involved in its anxiolytic effects observed in behaviour tests.