Risk of anaphylaxis in complementary and alternative medicine.

PURPOSE OF REVIEW: Complementary and alternative medicine (CAM) use is widespread across the world. Patients with asthma and allergy regularly use CAM therapies. Allergic and anaphylactic reactions to CAM have been reported. RECENT FINDINGS: Recent attempts to regulate and monitor adverse reaction to these therapies have given us further insight into potential causes of severe allergic reactions. Several culprits identified including Andrographis paniculata, Echinacea species, bee products, Ginkgo biloba and Ginseng are discussed here. SUMMARY: Knowing the factors that increase the risk of anaphylaxis allows reactions to be recognized, reported and further investigated. Research to identify key causative allergens is necessary in the future. Collaboration between the allergy community and CAM practitioners can allow better understanding of allergy to these therapies.

Activities and Prevalence of Proteobacteria Members Colonizing Echinacea purpurea Fully Account for Macrophage Activation Exhibited by Extracts of This Botanical.

Evidence supports the theory that bacterial communities colonizing Echinacea purpurea contribute to the innate immune enhancing activity of this botanical. Previously, we reported that only about half of the variation in in vitro monocyte stimulating activity exhibited by E. purpurea extracts could be accounted for by total bacterial load within the plant material. In the current study, we test the hypothesis that the type of bacteria, in addition to bacterial load, is necessary to fully account for extract activity. Bacterial community composition within commercial and freshly harvested (wild and cultivated) E. purpurea aerial samples was determined using high-throughput 16S rRNA gene pyrosequencing. Bacterial isolates representing 38 different taxa identified to be present within E. purpurea were acquired, and the activity exhibited by the extracts of these isolates varied by over 8000-fold. Members of the Proteobacteria exhibited the highest potency for in vitro macrophage activation and were the most predominant taxa. Furthermore, the mean activity exhibited by the Echinacea extracts could be solely accounted for by the activities and prevalence of Proteobacteria members comprising the plant-associated bacterial community. The efficacy of E. purpurea material for use against respiratory infections may be determined by the Proteobacterial community composition of this plant, since ingestion of bacteria (probiotics) is reported to have a protective effect against this health condition.

Immunopharmacology of the main herbal supplements: a review.

It is debated whether the use of herbal supplements in endurance sports, in order to have a better performance, is correct or not, from the perspective of both as safety and as effectiveness. In this review we try to find out if the most common herbal supplements (Echinacea, Rhodiola, Ginseng) are effective in the improvement of performance or in the modulation of the immune system. According to the results of our review, the prevalent effect is adaptogenic rather than ergogenic, with a better tolerance of the exercise induced stress, related to enhancement of the whole immune system and decrease of the oxidative damage.

Characterization and immunolocalization of arabinogalactan-proteins in roots of Echinacea purpurea.

From the high molecular weight fraction of an aqueous extract from roots of Echinacea purpurea L. Moench, arabinogalactan-proteins (AGPs), a class of proteoglycans proposed to be involved in cell differentiation and plant growth, were purified and characterized with regard to amino acid composition and structure of the polysaccharide moiety. The protein content of the AGP was 5.0 % (w/w) with the dominating amino acids Glx, Hyp, Asx, Ser, Thr and Ala. The highly branched polysaccharide moiety shows a linkage composition typical of AGPs with 1,3-, 1,6- and 1,3,6-linked galactopyranosyl residues and arabinofuranosyl residues predominantly as terminal and 1,5-linked residues. Terminal units of glucuronopyranose acid were also detected. Furthermore, a new method for the localization of AGPs in plant tissue has been developed. The synthetic (beta- D-Glc)(3) Yariv phenylgycoside (betaGlcY) is known to specifically bind to AGPs. For immunolocalization, polyclonal betaGlcY-antibodies have been generated and were used to label Yariv-treated thin sections of roots from E. purpurea. After addition of the FITC-conjugated secondary antibody, the sections were analyzed by confocal laser scanning microscopy. AGPs are detected mainly in the central cylinder in the area of the xylem. Cell walls of vessels and tracheids are strongly labelled, especially at the inner area of the wall. Furthermore, there is intense labelling of the pit canals.

Synthesis of 3,6-branched arabinogalactan-type tetra- and hexasaccharides for characterization of monoclonal antibodies.

Synthesis of tetra- and hexasaccharides built up from a beta-(1-->6)-linked galactopyranosyl backbone with arabinofuranosyl side chains at position 3 and with a 3-aminopropyl spacer related to arabinogalactans is described. These oligosaccharides were prepared for investigation of monoclonal antibodies raised against arabinogalactan proteins (AGPs) from pressed juice of Echinacea purpurea.

Effects of echinacea on the frequency of upper respiratory tract symptoms: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Upper respiratory tract infection symptoms are a common cause of morbidity. Herbal preparations of the plant Echinacea purpurea have immune-enhancing properties. OBJECTIVE: To compare the frequency of upper respiratory tract symptoms in individuals receiving E. purpurea capsules and those receiving placebo to evaluate the preventive efficacy of echinacea. METHODS: In a randomized, double-blind clinical trial, 90 volunteers recruited from hospital personnel were randomly assigned to receive 3 capsules twice daily of either placebo (parsley) or E. purpurea for 8 weeks during the winter months. Upper respiratory tract symptoms were reported weekly during this period. RESULTS: Fifty-eight individuals were included in the final data analysis: 28 in the echinacea group and 30 in the placebo group. Individuals in the echinacea group reported 9 sick days per person during the 8-week period, whereas the placebo group reported 14 sick days (z = -0.42; P = .67). Mild adverse effects were noted by 8% of the echinacea group and 7% of the placebo group (P = .24). CONCLUSION: Prophylactic treatment with commercially available E. purpurea capsules did not significantly alter the frequency of upper respiratory tract symptoms compared with placebo use.

Use of quantitative flow cytometry to measure ex vivo immunostimulant activity of echinacea: the case for polysaccharides.

INTRODUCTION: When directly exposed to various echinacea fractions, human leukocytes ex vivo are strongly stimulated to proliferate and to produce immunostimulation and inflammatory cytokines. A comparison of fractions containing lipoidal small molecules and high-molecular-weight water-soluble polysaccharides indicates that the latter are substantially more potent as immunostimulants. Echinacea purpurea (L.) Moench, E. angustifolia DC, and E. pallida (Nutt.), Nutt. extracts, and each plant part contain significantly potent constituents. Flow cytometric techniques were utilized. OBJECTIVES: This study was undertaken to determine whether flow cytometry could measure immunostimulant activity present in echinacea and, if so, which species produced more activity, which plant part was the most active, and whether the organic soluble or the aqueous extractables were more active. Ex vivo human clinical material was employed. DESIGN: Echinacea extracts were analyzed using flow cytometric techniques. The immunostimulation assays were measured in triplicate. METHODS: Samples dissolved in dimethyl sulfoxide (DMSO) were added to 200 microL of heparinized blood mixed with 50 muL of phosphate buffer, vortexed, and incubated to allow adequate time for immune-cell stimulation. Fifty (50) microL of the stimulated blood samples were added to each of a reagent cocktail consisting of 20 microL of CD4FITC/CD69PE/CD3PerCP expressed on the helper/inducer T-lymphocyte subset; CD8FITC/CD69/PE/ CD3PerCP expressed on the human suppresser/cytotoxic T-lymphocytes and on a subset of natural killer lymphocytes; CD19FITC/CD69PE/CD45PerCP expressed on B-lymphocytes; or CD56FITC/CD69PE/CD45PerCP expressed on NK lymphocytes. Four hundred and fifty (450) microL of 1 X FACS lysing solution was added and incubated in the dark (rt, 30 minutes) and then subjected to flow cytometric analysis. All reported readings are the average of several determinations. Positive controls consisted of phorbol myristyl acetate (PMA) (50 ng/mL), phytohemagglutinin (10 microg/mL), CD2/CD2R (positive activation control)(5 microL/250 muL of reaction), and negative controls consisted of dimethyl sulfoxide (2% in RPMI-1640), RPMI-1640 medium, and cyclosporin A (10 microg/mL). RESULTS: The main immunostimulatory activity of echinacea resides in the water-soluble materials rather than the lipoidal small molecules. E. purpurea, E. Pallida, and E. angustifolia leaves, stems, flowering tops, and roots all produce substantial immunostimulatory activity. CONCLUSIONS: The use of flow cytometry demonstrates a link between the polysaccharides in echinacea and the biologic immunostimulatory effect that has therapeutic relevance, and strong evidence for this immunostimulant property is presented.

Alkylamides from echinacea modulate induced immune responses in macrophages.

The ability of Echinacea and its components to alter the immune response was examined in vitro in a macrophage cell line under either basal or immunostimulated conditions. Potential immunostimulatory and inflammatory activity was determined using a nuclear transcription factor (NFkappaB) expression, tumour necrosis factor alpha (TNFalpha) and nitric oxide (NO) production as biomarkers. In the absence of alternate stimulation, the only significant effects seen were a decrease in NFkappaB expression by a 2-ene alkylamide ((2E)-N-isobutylundeca-2-ene-8,10-diynamide (1)) and a decrease in TNFalpha levels by cichoric acid and an Echinacea alkylamide fraction (EPL AA). When the cells were stimulated by lipopolysaccharide (LPS), inhibition of the increased NFkappaB expression levels was caused by cichoric acid, an Echinacea preparation (EPL), EPL AA and a 2,4-diene ((2E,4E,8Z,10Z)-N-isobutyldodeca-2,4,8,10-tetraenamide (2)). Increases in TNFalpha levels were inhibited by cichoric acid, EPL and EPL AA but enhanced by 1 in the presence of LPS, while only EPL AA was able to inhibit the stimulated increases in NO. When using phorbol myristate acetate to stimulate the cells, NFkappaB and NO levels were unaffected by Echinacea or its components while only cichoric acid and 2 inhibited TNFalpha levels. Although cichoric acid was found to have an effect, it is probably not an important contributor to the Echinacea modulation of the immune response in vivo, as it is not bioavailable. Echinacea appears to attenuate the response of macrophages to an immune stimulus and its combination of phytochemicals exhibits different pharmacological properties to one or more of the isolated major individual components.

Dietary consumption of Echinacea by mice afflicted with autoimmune (type I) diabetes: effect of consuming the herb on hemopoietic and immune cell dynamics.

Epidemiological studies indicate that the incidence of Type 1 diabetes, an autoimmune disease, is rising rapidly. However, none of the current therapies produces life long remission, or can prevent the disease onset. The NOD (non-obese diabetic) mouse is currently regarded as an excellent animal model of human Type 1 diabetes. NKT cells are known to be fundamental in modulating the disease, yet they are numerically and functionally deficient in mammals bearing this disease. Indeed, the role of NK cells in inhibiting autoimmunity in general is well established. Immunoregulatory strategies are currently believed to be the way of the future with respect to modulating autoimmune diseases. Based on this hypothesis, and the fact that the herb, Echinacea, is a well demonstrated immunostimulant of NK cells in normal mice/humans, we aimed to investigate, in NOD mice, the effect of short term (days) and long term (months) daily dietary administration of Echinacea, on the absolute levels of NK cells, and five other classes of hemopoietic and immune cells, in the bone marrow and spleen. The results revealed that, in NOD mice, dietary Echinacea, resulted in a significant increase in the absolute numbers of NK cells, irrespective of feeding duration, in the spleen, and moreover, it actually stimulated NK cell production in their bone marrow birth site. We further found that there were transient, early (days), herb exposure-time-dependent, quantitative changes in several of the other hemopoietic and immune cells populations in both the bone marrow and spleen. We conclude that consumption of this herb by NOD mice, at least, has lead to no negative repercussions with respect to the hemopoietic and immune lineages, and secondly, the consistent, long-lasting immunostimulation only of NK cells, may lead to a possible new approach to the treatment of Type 1 diabetes.

Immunological and haematinic consequences of feeding a standardised Echinacea (Echinacea angustifolia) extract to healthy horses.

This study was undertaken to compile new data on the efficacy of Echinacea in stimulating the immune system of the horse. Use of Echinacea is becoming widespread in horses, despite an absence of controlled laboratory research into its effectiveness or safety. This paper documents results of a double-blind, placebo-controlled, cross-over trial investigating the effect of standardised Echinacea extract on 8 horses. Animals were supplemented with Echinacea or placebo for 42 days, and their response to supplements recorded. Treatment with Echinacea increased phagocytic ability of isolated neutrophils, boosted peripheral lymphocyte counts and appeared to stimulate neutrophil migration from peripheral circulation into the tissues. Echinacea supplement also increased the size and concentration of peripheral red blood cells, and the concentration of haemoglobin and packed cell volume. It was concluded that Echinacea effectively stimulates equine immunocompetence, and the plant extract behaves, in equine subjects, as a haematinic agent, i.e. one which improves the quality of blood by increasing haemoglobin levels and the number of erythrocytes and which, by virtue of their effects on oxygen transport cells, are considered to improve parameters of exercise physiology and performance.

The effect of immunization with killed tumor cells, with/without feeding of Echinacea purpurea in an erythroleukemic mouse model.

OBJECTIVE: Tumor amelioration via vaccination/immunization is a practice for which considerable experimental and clinical support is growing. Combination therapies have proven to be more beneficial than treatment with single agents. We hypothesized that immunization of mice with killed erythroleukemia cells prior to the induction of erythroleukemia via injection of viable tumor cells, plus dietary administration of a known immuno-enhancing phytocompound, Echinacea purpurea, would be more effective than immunization alone. DESIGN: A commercially available extract of E. purpurea root, already proven as a natural killer (NK) cell stimulant, was administered via the chow, for periods of 9 days or 3 months after the onset of leukemia to mice which had been injected (immunized) 5 weeks earlier with killed leukemia cells. RESULTS: Immunized mice (+/- E. purpurea) had significantly prolonged life spans versus non-immunized mice, with an even greater proportion of hosts surviving long-term in the E. purpurea-fed group. NK cells, the mediators of nonspecific immunity and well-demonstrated mediators of tumor cytolysis, were very significantly elevated in immunized, leukemic mice receiving E. purpurea in their diet versus those receiving untreated chow. Early in tumor development (9 days), cells mediating specific immunity (T, B lymphocytes) were 10-12 times higher in absolute numbers in the spleens in all immunized, leukemic mice vs unimmunized, leukemic mice at the same stage of tumor progression. CONCLUSIONS: The results demonstrate that combination therapy, involving specific tumor cell immunization, followed by daily phytotherapy (dietary E. purpurea), sensitized the immune cells and led to life span prolongation greater than that provided by immunization alone.

Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats.

Echinacea plant extract is widely used for the prevention and the treatment of upper respiratory tract infections. However, the active components in the herb, their optimal dosages and their in vivo effects are still undefined. Using male Sprague-Dawley rats (425-475 g), an in vivo study was conducted to examine the immunomodulatory effects of various dose levels of three components, isolated and purified from Echinacea purpurea. The components were cichoric acid, polysaccharides and alkylamides. The rats were gavaged orally two times/day for 4 days with three different concentrations of each of the Echinacea components. Among the components, alkylamides at the dose level of 12 microg/kg body weight/day significantly increased the phagocytic activity as well as phagocytic index of the alveolar macrophages. The alveolar macrophages obtained from this group of rats also produced significantly more TNF-alpha and nitric oxide after an in vitro stimulation with LPS than any other active component or the control. None of the components at any concentration had any effect on the release of TNF-alpha, IFN-gamma and IL-2 by the splenocytes. These results suggest that the alkylamides are one of the active constituents of E. purpurea plant. At a dose level of approximately 12 microg/kg body weight/day they effectively stimulate alveolar macrophage function in healthy rats. The immunomodulatory effects of alkylamides appear to be more pronounced in lungs than in spleen.