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The immunostimulating effect by ingestion of an Echinacea Purpurea preparation
Abstract
In the present study, we investigated whether oral ingestion of Echinacea purpurea improves human immunity, especially of NK. cells, T-lymphocyte, and B-lymphocyte. Twenty two healthy volunteers, who feel fatigue daily, participated in our trial, and were randomly assigned to either the echinacea group or placebo group. The echinacea group ingested a preparation of Echinacea purpurea which consisted of 500mg of extracts of Echinacea purpurea and 1500 mg of diluents, whereas the placebo group ingested a placebo which consisted of 2000mg of diluents. Each participant ingested test products once a day before sleeping, for 3 weeks. We inspected the participants' immunity at initial, 1 week, and 3 weeks after the ingestion. Scoring of Immunological Vigor, which is the comprehensive assessment of human immunity, significantly improved only in the echinacea group (p= 0.030). As compared with the initial level, the growth of the numbers of lymphocytes (p=0.035) and CD4+ T-ce!ls (p=0.050) in the echinacea group at 3 weeks after the initiation of ingestion significantly increased more than those in the placebo group, and the growth of the number of T-cells (p=0.060) showed the same tendency with marginal significance. However, the number of NK-cells and its activity in both groups decreased, and the number of B-cells did not show any significant change. In summary, our results indicate that preparation of Echinacea purpurea could improve the immunological function of humans, especially in T-lymphocyte.
... The values of these immune parameters were standardized by assigning scores of 3 (high), 2 (moderate), or 1 (low) . SIV has already been used to evaluate the immunomodulating influences of supplements and fruits in a Japanese population (Fujii et al., 2011;Suzuki et al., 2012). As SIV is calculated using multiple factors, it can describe 'comprehensive immunity' by considering eight parameters and not interpreting each immune function separately. ...
... Sample size estimation and statistical analysis. A sufficient sample size of 42 subjects per group was determined through a power analysis of previous data used to evaluate SIVs (Fujii et al., 2011;Suzuki et al., 2012;unpublished data), with the following settings: statistical power of 80%, significance level of p < 0.05, and mean difference in the change in SIV between the two groups of two-thirds the standard deviation (SD), with an allocation ratio of 1:1 and the assumption of an approximate dropout rate of 20% per group. This estimation was performed using the EZR package ver. ...
This study was aimed to investigate the capacity of a standardized root water extract of Eurycoma longifolia (Tongkat Ali, TA), Physta® to modulate human immunity in a middle-aged Japanese population. This randomized, double-blind, placebo-controlled, parallel study was conducted for 4 weeks. Eighty-four of 126 subjects had relatively lower scores according to Scoring of Immunological Vigor (SIV) screening. Subjects were instructed to ingest either 200 mg/day of TA or rice powder as a placebo for 4 weeks [TA and Placebo (P) groups] and to visit a clinic in Tokyo twice (weeks 0 and 4). SIV, immunological grade, immunological age, and other immune parameters were measured. Eighty-three subjects completed the study; 40 in the TA group and 41 in the P group were statistically analyzed, whereas two were excluded from the analyses. At week 4, the SIV and immunological grade were significantly higher in the TA group than those in P group (p < 0.05). The numbers of total, naïve, and CD4(+) T cells were also higher in the TA group than those in P group (p < 0.05). No severe adverse events were observed. The results suggest that ingestion of the root water extract of TA (Physta®) enhances comprehensive immunity in both middle-aged men and women. This study is registered in UMIN-CTR (UMIN000011753). Copyright © 2016 John Wiley & Sons, Ltd.
... 17 The same preparation improved immunological function in humans, especially T cell-related immunity. 18 However, the modulatory effects of Echinacea on restraint stressinduced immunosuppression in mice have not yet been tested. Therefore, we aimed to investigate the effects of Echinacea on immune function in restrained mice, with an emphasis on splenocyte proliferation and NK cell activity in the spleen and on blood T lymphocyte subsets and cytokine production. ...
Echinacea purpurea has been widely used for the prevention and treatment of upper respiratory tract infections and the common cold. The restraint stress has been reported to suppress a broad spectrum of immune functions. The aim of this study was to investigate the protective effects of the pressed juice of E. purpurea (L.) Moench (EFLA®894; Echinacea) against restraint stress-induced immunosuppression in BALB/c mice. Echinacea significantly normalized the restraint stress-induced reduction in splenocyte proliferation and splenic natural killer (NK) cell activity (P < .05). Echinacea treatment significantly increased the percentages of CD4+ and CD8+ T lymphocytes in the blood (P < .05). In addition, Echinacea restored serum cytokine levels, including interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17), as well as the mRNA expressions of these cytokines in spleen (P < .05). Our findings suggest that Echinacea might have beneficial effects on restraint stress-induced immunosuppression by increasing splenocyte proliferation and NK cell activity, while modulating T lymphocyte subsets and cytokine levels in the blood.
Elevated neutrophil/lymphocyte ratio (NLR) has been reported as a sensitive marker for predicting poor prognosis in chronic inflammation-based diseases such as stroke, heart failure, cancers, and diabetes, as well as acute inflammatory diseases such as bacterial and viral infections, including COVID-19. NLR is also known to increase with age and is considered to be an aging marker. We conducted a double-blind, placebo-controlled trial in elderly volunteers to examine the effect of a newly developed, highly bioavailable curcumin formulation (curcuRougeTM) on NLR. Both the white blood cell count and the neutrophil rate decreased significantly, and the lymphocyte rate increased significantly from baseline to after curcuRougeTM administration for 4 wk. curcuRougeTM significantly reduced the NLR (p=0.020). On the other hand, in the placebo group, there were no changes in white blood cell count, neutrophil ratio, lymphocyte ratio, or NLR. The present study demonstrates for the first time, in elderly volunteers, that administration of curcuRougeTM significantly reduces NLR, an indicator of prognosis in cardiovascular diseases, cancer, infectious diseases, and aging. Thus, curcuRougeTM might be expected to improve the prognosis of these diseases as well as exhibit anti-aging effects.
Upper respiratory tract infections (URTI) frequently cause exacerbations of chronic-obstructive pulmonary disease (COPD). Stimulation of the innate immune system may provide an early defence against such infections. The objective of this study was to determine whether Echinacea purpurea (EP) along with micronutrients may alleviate COPD exacerbations caused by acute URTI.
This was a double-blind, randomized, placebo-controlled trial in COPD patients with acute URTI. Patients were given ciprofloxacin for 7 days and additionally one tablet per day of EP, of EP along with zinc, selenium and ascorbic acid (EP+), or of placebo until day 14. Serum levels of TNF α and interleukins 1β, 6 and 10 were measured before and after treatment. Until week 4 post-end of treatment, all patients had to daily report on COPD symptoms in diaries.
In total, 108 mostly male patients with a mean age of 65·8 years (40-81 years) were enrolled. Patients of the three treatment arms did not vary significantly in baseline characteristics. EP+, but not EP resulted in significantly less severe and shorter exacerbation episodes following URTI as compared with placebo suggesting a synergistic effect of Echinacea and micronutrients. Large variations in biomarkers in-between and within groups were unrelated to treatment. Study medication was safe and well tolerated with overall 15 adverse events one of which was serious. Among those, sleeping disorders were most frequent and likely related to the underlying disease.
The combination of EP, zinc, selenium and vitamin C may alleviate exacerbation symptoms caused by URTI in COPD. Further studies are warranted to investigate the interactions among Echinacea, zinc, selenium and vitamin C.
Purified polysaccharides (EPS) prepared from the plant Echinacea purpurea are shown to strongly activate macrophages. Macrophages activated with these substances develop pronounced extracellular cytotoxicity against tumor targets. The activation is brought about by EPS alone and is independent of any cooperative effect with lymphocytes. Also the production and secretion of oxygen radicals and interleukin 1 by macrophages is increased after activation with EPS. Cells of the macrophages lineage seem to be the main target for the action of these polysaccharides. EPS has no effect on T lymphocytes. B lymphocytes show a comparatively modest proliferation after incubation with E. purpurea EPS. Thus, these compounds, which are at least in tissue culture completely nontoxic, may be suited to activate in vivo cells of the macrophage system to cytotoxicity. They may therefore be of relevance in tumor and infectious systems.
The three leading causes of death in Japan are cancer, stroke and ischemic heart diseases. These data are mainly based upon reports by clinical doctors without conducting autopsy examination. An autopsy examination is performed in a small percentage of cases, less than 3% in Japan, but has revealed that infection is the top cause of death in the elderly. The information indicates that immunological vigor declines with advancing age and the immunodeficiency status is severe in many older adults. It is of clinical importance that many kinds of stress, in addition to aging, considerably down-regulate the immunological functions; this is especially prominent when the stress is unavoidable and continuing, but the effect varies greatly among different individuals. The immune status of individuals is usually expressed by a panel of various immunological parameters of different criteria and not easily understood by those who are not familiar with the immune system. We have developed a scoring method to standardize various immunological parameters, to combine them and to express the immune status of individuals as a simple numeral, termed immunological vigor. Using this scoring method, it becomes easy to assess the immune status of healthy individuals and patients, and to observe the effects of drugs, foods, drinks, physical exercise and supplements on their immunological vigor. This scoring method has revealed that immunological vigor significantly declined in patients suffering from colon cancer (stage 0-IV). The final part of this chapter introduces several methods of immunological restoration as follows: (1)Nutrition, (2)Supplements including antioxidants, (3)Hormones, (4)Vaccine, (5)Japanese herbal medicine (Kampohozai), (6)Infusion of activated autologous T cells, and (7)Music therapy.Proper, objective assessment of immunological vigor as a whole is indispensable for the maintenance of health, prognosis of diseases, effects of therapy and immunological restoration.
In living beings, external stimuli elicit a behavioral, verbal, or physiological response. The stimuli can be classified into
2 types: ordinary stimuli such as sound, smell, sight, and touch that are received by the sensory organs and pathological
stimuli such as bacterial, viral, and fungal infections that are received by the immune system (Fig. 1).
In this study, acidic arabinogalactan, a highly purified polysaccharide from plant cell cultures of Echinacea purpurea, with a molecular weight of 75, 000, was effective in activating macrophages to cytotoxicity against tumor cells and micro-organisms
(Leishmania enriettii). Furthermore, this polysaccharide induced macrophages to produce tumor necrosis factor (TNF-α), interleukin-1 (IL-1), and
interferon-β2. Arabinogalactan did not activate. B cells and did not induce T cells to produce interleukin-2, interferon-β2, or interferon-γ, but it did induce a slight increase in T-cell proliferation. When injected ip, this agent stimulated macrophages,
a finding that may have therapeutic implications in the defense against tumors and infectious diseases. [J Natl Cancer Inst
81: 669–675, 1989]
This article describes and discusses five placebo-controlled randomized studies investigating the immunomodulatory activity of preparations containing extracts of Echinacea in healthy volunteers. A total of 134 (18 female and 116 male) healthy volunteers between 18 and 40 years of age were studied. Two studies tested intravenous homeopathic complex preparations containing Echinacea angustifolia D1 (study 1) and D4 (study 5). Two studies (2 and 3a) tested oral alcoholic extracts of roots of E. purpurea, one study an extract of E. pallida roots (study 3b), and one study an extract of E. purpurea herb (study 4). Test and placebo preparations were applied for four (study 5) or five (studies 1-4) consecutive days. The primary outcome measure for immunomodulatory activity was the relative phagocytic activity of polymorphonuclear neutrophil granulocytes (PNG), measured in studies 1 and 2 with a microscopic method and in studies 3, 4, and 5 with two different cytometric methods. The secondary outcome measure was the number of leukocytes in peripheral venous blood. Safety was assessed by a screening program of blood and other objective parameters as well as by documentation of all subjective side effects. In studies 1 and 2 the phagocytic activity of PNG was significantly enhanced compared with placebo [maximal stimulation 22.7% (95% confidence interval 17.5-27.9%) and 54.0% (8.4-99.6%), respectively], while in the other studies no significant effects were observed. Analysis of intragroup differences revealed significant changes in phagocytic activity during the observation periods in five test and three control groups. Leukocyte number was not influenced significantly in any study. Side effects due to the test preparations could not be detected. Our studies provide evidence for immunomodulatory activity of the homeopathic combination tested in study 1 and the E. purpureae radix extract tested in study 2. The negative results of the other three studies are difficult to interpret due to the different methods for measuring phagocytosis, the relevant changes in phagocytic activity within most placebo and treatment groups during the observation period, and the small sample sizes. Future studies should be performed on patients rather than healthy volunteers and use standardized or chemically defined monopreparations of Echinacea.
Preparations from Echinacea purpurea are among the most widely used herbal medicines. Most uses of E. purpurea are based on the reported immunological properties. A series of experiments have demonstrated that E. purpurea extracts do indeed demonstrate significant immunomodulatory activities. Among the many pharmacological properties reported, macrophage activation has been demonstrated most convincingly. Phagocytotic indices and macrophage-derived cytokine concentrations have been shown to be Echinacea-responsive in a variety of assays. Activation of polymorphonuclear leukocytes and natural killer cells has also been reasonably demonstrated. Changes in the numbers and activities of T- and B-cell leukocytes have been reported, but are less certain. Despite this cellular evidence of immunostimulation, pathways leading to enhanced resistance to infectious disease have not been described adequately. Several dozen human experiments--including a number of blind randomized trials--have reported health benefits. The most robust data come from trials testing E. purpurea extracts in the treatment for acute upper respiratory infection. Although suggestive of modest benefit, these trials are limited both in size and in methodological quality. Hence, while there is a great deal of moderately good-quality scientific data regarding E. purpurea, effectiveness in treating illness or in enhancing human health has not yet been proven beyond a reasonable doubt.
In spite of Echinacea-based products being among the best-selling herbs in the world to date, to allay assorted ailments, the debate is still on-going with respect to the efficacy of ingesting the herb intermittently, continuously, or only at the beginning of an affliction. We sought, therefore, to find out if mice, receiving dietary Echinacea daily, throughout life, from youth until late middle-age, demonstrated any longevity/survival differences, and/or any differences in their various populations of immune/ hemopoietic cells. Sustained and/or high levels of these cells are crucial for longevity. Some mice were maintained on a regular chow diet to which was added Echinacea purpurea daily (2 mg/mouse), from puberty (7 week) until just beyond 13 months of age (late middle-age in mice). Control mice, identically housed and maintained, received identical chow without the herb. Mice consuming untreated diet had a 79% survival by 10 months of age, while those consuming Echinacea daily in the diet were still 100% alive by 10 months. At approximately 13 months of age, mice consuming untreated diet had a 46% survival rate while those consuming Echinacea, were 74% alive at this time. Moreover, the key immune cells, acting as the first line of defense against developing neoplasms in mice and humans, i.e., natural killer (NK) cells, were significantly elevated in absolute number both in their bone marrow production site, as well as in the major organ to which they traffic and function, i.e., the spleen. The cells of the myeloid/granulocyte lineages remained steadfastly at control levels in both the bone marrow and spleen in Echinacea-consuming mice. Thus, it appears that regular intake of Echinacea may indeed be beneficial/prophylactic, if only for the reason that it maintains in an elevated state, NK cells, prime elements in immunosurveillance against spontaneous-developing tumors, a phenomenon which increases in frequency with progressive aging.
In a previous paper, it was reported that Echinilin (Factors R & D Technologies, Burnaby, British Columbia, Canada) a formulation prepared from freshly harvested Echinacea purpurea plants and standardized on the basis of three known active components (alkamides, cichoric acid and polysaccharides) is effective for the treatment of a naturally acquired common cold. However, the mechanism by which this effect is achieved remains unknown. In the present study, Echinilin or placebo were administered to volunteers at the onset of their cold for a period of 7 days, with eight doses (5 mL/dose) on day 1 and three doses on subsequent days. Fasting blood samples were obtained before and during their colds. The decrease in total daily symptomatic score was more evident in the echinacea group than in the placebo group. These effects of echinacea were associated with a significant and sustained increase in the number of circulating total white blood cells, monocytes, neutrophils and NK cells. In the later part of the cold, the echinacea treatment suppressed the cold-related increase in superoxide production by the neutrophils. These results suggest that Echinilin, by enhancing the non-specific immune response and eliciting free radical scavenging properties, may have led to a faster resolution of the cold symptoms.
Background:
In a recent double-blind placebo-controlled crossover-study the "immune stimulatory" effects (activation of macrophages leading to enhanced phagocytosis and production of several cytokines) of Echinacea purpurea preparations (EPP) which were observed in vitro experiments and following parenteral administration could not be confirmed following oral application of the drug in healthy volunteers. The aim of the present study was to investigate whether or not oral EPP has any effect on important lymphocyte-subpopulations.
Subjects and methods:
Forty healthy male volunteers (age range 20-40 years) participated in the study. They received either a commercially available pressed juice of E. purpurea herbs or placebo juice using a double-blind placebo-controlled cross-over design with two treatment periods of 14 days. The total number of lymphocytes and 12 subgroups of lymphocytes were determined by using Flow-cytometry.
Results:
After 1 week of treatment with verum the mean value of the total number of lymphocytes decreased slightly (-6%, p = 0.033) compared to the initial value. Treatment for 1 and 2 weeks with EPP had only minor effects on two of the 12 subtypes of lymphocytes. No significant changes were observed in the verum period for the following types of cells: T- and B-lymphocytes, CD4 + - and CD8 + -T-lymphocytes including the subgroups of "naive" and "memory" CD4 + - and CD8 + -T-lymphocytes as well as the natural killer cells. Using a modified version of the Wilcoxon-Mann-Whitney-U-test, which is claimed to be optimal for the evaluation of the results of studies with a cross-over design, a significant difference was found for the number of CD8 + -T-lymphocytes and natural killer cells corresponding to either a decrease during treatment with verum or an increase in the number of these cells in the placebo period.
Conclusion:
Oral administration of EPP for 1 and 2 weeks has only minor effects on two out of 12 lymphocyte subpopulations determined in the study. The small differences observed in the number of CD8 + -T lymphocytes and natural killer cells are only of questionable physiological relevance.
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