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The effect in humans of three immune stimulating herbs.

Brush J, Mendenhall E, Guggenheim A, Chan T, Connelly E, Soumyanath A, Buresh R, Barrett R, Zwickey H. The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans. Phytotherapy Research 2006;20(8):687--695.


Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra are well-known to herbalists for, among other actions, their immunostimulating properties. However, as these authors note, most of the research regarding the mechanisms by which these herbs positively influence the immune system has been conducted in animal models. Thus, these researchers set out to establish the efficacy of these herbs using a human model.


The researchers designed a small pilot study to measure what activation, if any, occurred on immune cellular activation markers in humans following oral administration of Echinacea, Astragalus and Glycyrrhiza. In particular, the researchers looked at the growth factor receptor CD69. The presence of CD69 indicates whether CD4, CD8, NK cells and B-cells (cells which are all involved in the body's immune responses) had been activated.

The main objective of the study was to determine if each herb increased CD69 expression when administered orally for seven days. A second objective was to determine if a synergistic effect existed when the herbs were used in combination.

Sixteen subjects (3 male, 13 female) took part in a placebo controlled double-blind study. Four of these subjects received Echinacea, four received Astragalus, three received Glycyrrhiza, three received a combination of all three herbs in equal parts, while two received a placebo. Identical flavours and colours were added to all tonics and placebos to produce final products with similar tastes and colours.

Extracts of fresh Echinacea and Astragalus roots, and dried Glycyrrhiza root were used. Dosages were 7.5 mL twice a day. This daily dose provided a dry herb equivalent of 0.93 g Echinacea, 1.23 g Astragalus and 0.87 g Glycyrrhiza.


CD69 expression was increased at 24 hours by all three herbs. This effect was strongest for Astragalus, followed by Echinacea and Glycyrrhiza. After seven days, this activation of CD69 had decreased for all three herbs, but remained higher than base line levels in the Echinacea and Astragalus subjects, but not in the Glycyrrhiza subjects. Subjects taking the placebo showed no increase in CD69 expression at 24 hours, but did show a slight increase on day 7, likely due to individual variability.

Further analysis allowed the researchers to determine which type of immune cells had been activated by the single herbs. Echinacea and Astragalus primarily stimulated CD8 T cells, and to a lesser extent CD4 T cells. Subjects taking Glycyrrhiza showed equal increases in activation of both CD4 and CD8 T cells, and also a smaller increase in NK cells. The placebo group showed little cell activation.

The subjects taking the combination tonic also showed increased CD69 activation, expressed primarily on CD8 T cells, and to a lesser extent on CD4 T cells and NK cells. Of note, the CD69 immune cell activation in the combination tonic subjects exceeded the levels seen in the subjects taking the individual herbs. Therefore, it seems that the three herbs taken together had a synergistic effect.

Additional analysis looked at what proliferation (as opposed to activation) of immune cells occurred. On this measure, Glycyrrhiza increased the total number of all the immune cells ie CD4 T cells, CD8 T cells, B cells, and NK cells. Subjects taking Echinacea showed increases in CD4 T cells, CD8 T cells and NK cells. Astragalus produced only slight increases in CD4 T cells and B cells, with slight decreases in CD8 T cells and NK cells. 'Thus even though Astragalus activated the cells, it did not cause their proliferation.' The subjects taking the combination tonic experienced increases in the numbers of CD4 T cells, CD8 T cells and NK cells.


The authors concluded that this study indicated that each of the three herbs activated CD4 T cells and CD8 T cells, and that this immune activation appeared greater when all three herbs were taken together. This activation might explain the efficacy of these herbs in mounting an effective immune response at the onset of viral and bacterial infections.

Additionally, CD69 expression is reduced with age-related deterioration of the immune system (immunosenescence). CD69 expression is also one of the factors affected in common variable immunodeficiency. Thus, these three herbs have the potential to increase CD69 expression in these conditions, and may assist in their management.
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Title Annotation:Herbal Medicine Review
Author:Boylan, Matthew
Publication:Journal of the Australian Traditional-Medicine Society
Article Type:Clinical report
Geographic Code:8AUST
Date:Jun 1, 2008
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