Use of a Standardized Extract from
Echinacea angustifolia for the
Prevention of Respiratory Tract Infections

FROM:   Alternative Medicine Review 2012 (Mar);   17 (1):   36–41 ~ FULL TEXT

Francesco Di Pierro, Giuliana Rapacioli, Tarcisio Ferrara, Stefano Togni

Scientific Director,
Velleja Research s.r.l.,
Via G. Natta, 28, 29010 Pontenure (PC);
f.dipierro@vellejaresearch.com

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Echinacea preparations are extensively used for the prevention and the management of the common cold. Despite this popularity, the clinical studies on Echinacea have produced mixed results, possibly in part because of the poor characterization of the extracts investigated and the use of different species and/or plant parts for the preparations investigated in the various trials. To address this issue, Polinacea®, a highly standardized extract from a well-defined botanical source (roots of Echinacea angustifolia) with a specific phytochemical profile (presence of the complex polysaccharide IDN5405, the phenylethanoid echinacoside, and substantial lack of alkamides) was developed. We have studied whether Polinacea® could enhance the immune response subsequent to the influenza vaccination, and whether the use of this preparation could translate into a decreased morbidity from influenza. The preliminary results were encouraging, and suggest that it could be used for improving the immune response to influenza vaccine.

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From the Full-Text Article:

Introduction

Preparations from Echinacea are used for the prevention and the treatment of the common cold; however, research on efficacy has produced mixed results. [1] In contrast to a large number of positive studies conducted according to a non-controlled design or on a limited population, controlled and wider-ranging studies have frequently yielded negative results, or, at best, have only suggested a positive trend for efficacy. [1] These mixed findings are not surprising, since the term “Echinacea-based preparations” encompasses extracts

(1) obtained using varying extraction methods and solvents,

(2) from different Echinacea species, and

(3) from different parts of these plants (e.g., aerial versus underground parts), with therefore marked differences in terms of constituent profiles.

There are three medicinal species of Echinacea (Echinacea angustifolia D.C., E. purpurea (L.) Moench, and E. pallida Nutt.). All three of these species can be found in at least some Echinacea products in the healthcare market. [2] The roots of these three species are difficult to distinguish from one another, which can lead to difficulty in botanical identification. In part because of confused botanical identification, a number of preclinical and/or clinical studies on Echinacea lack botanical traceability and the exact species of Echinacea used cannot be determined. [1] This is a critical issue, since substantial phytochemical differences exist between the three commercial species of Echinacea, and within each species between the aerial and underground parts. Furthermore, the phytochemical profile of all Echinacea plant parts is characterized by the presence of compounds that span a wide range of polarities, and with often opposite, rather than complementary bioactivity (i.e., some constituents are water-soluble and are extracted better using certain methods or solvents, while others are lipid-soluble and would be poorly extracted using these same methods or solvents). [3] Generally, the polar and water-soluble polysaccharides – which are shared by all three species – have immunostimulating properties, while the lipophilic alkamides (isobutylamides) – typical of E. angustifolia and E. purpurea – have a powerful anti-inflammatory action, mediated by the activation of the peripheral cannabinoid receptor. [4] Consequently, consumption of isobutylamide-rich Echinacea preparations may contribute to mitigation of the inflammatory response during an infection in progress, but might not exert any immuno-stimulating or preventive action on morbidity. [5] When this information is combined with their chemical instability [5] and the current limited knowledge of their toxicity, it provides a rationale for removing alkamides from Echinacea extracts intended to be used exclusively for immuno-stimulating purposes.

From the standpoint of preventing respiratory tract infections, the most interesting Echinacea constituents appear to be the polysaccharides and echinacoside (a polyphenol conjugate). [1] The polysaccharide fraction of various species of Echinacea is a powerful activator of the alternative route of the complement system – a non-specific defense mechanism – and of cytokines capable of triggering macrophage activation. [1] These effects increase objective immunological parameters, like the number of T cells, the plasma levels of neutrophils, the macrophage phagocytosis index, as well as the activity of natural killer cells. [1] Echinacoside is also a weak antibacterial agent that can inhibit bacterial hyaluronidase, [5, 6] a class of enzymes necessary for bacteria to spread through the skin and mucosal membranes.

To address the uncertainties of composition that plague so many commercial Echinacea preparations, a specific botanical preparation was developed from the roots of E. angustifolia, the most researched Echinacea species in terms of its ethnopharmacological and medicinal uses. [7] Polinacea® is a hydro-alcoholic extract obtained from the roots of this plant. It is triply standardized for echinacoside (>2%), IDN5405 (>5%), and alkamides (< 0.1%).8 [Note: IDN5405 is a polysaccharide characterized by a highly branched galacturonic structure, well distinct from the endophytederived lipopolysaccharides ubiquitous in plant tissues.]

Since this standardized Echinacea preparation is intended for long-term prophylactic use as a means to improve immune system performance, the profile of the product is intentionally kept very low in its contents of alkamides. Part of the rationale for this decision is that, while these compounds have shown powerful immuno-stimulating activity in vitro, as exemplified by the stimulation of IFN-? production by T lymphocytes (not by other types of lymphocytes), they might be inactive in vivo. [8] The anti-inflammatory and cytokine-inhibiting properties of alkamides, [4] though undoubtedly useful for the mitigation of symptoms once an infection is in progress, [5] might also potentially be, in fact, either neutral or counter-productive in products aimed at the prevention of infections. [5] The peculiar composition of Polinacea® was established using cell assays, and was then validated at the pre-clinical level using an animal model (Candida sp. infection in normal- or cyclosporine- treated immunosuppressed mice). In this model, common endophytic bacterial lipopolysaccharides, usually active on macrophages, proved totally inactive. [8]

There has been a growing interest for natural products capable of modulating the strength and the duration of the immune response, in particular linked to seroconversion subsequent to vaccinations. [9] Most studies in this area have been done using extracts containing saponins or polysaccharides of bacterial/fungal origin, frequently in association with polyphenols. [10] The preliminary results obtained from studies in this area provide a rationale for assessment of other natural products, which might potentially augment the immune response to vaccinations. This research was undertaken to provide preliminary data on whether Polinacea® might augment the immune response to influenza vaccination, [11] and whether its use would have any clinical relevance in terms of influenza morbidity in instances where vaccination was not administered.

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Discussion

In order to avoid the issues of (1) poor characterization of constituents used, and (2) ambiguity of the source of the Echinacea being used, we used a standardized Echinacea preparation (triple standardization for IDN5405 >5%, echinacoside >2%, and alkamides <0.1%) that was derived exclusively from underground parts from a single source of known botanical origin (E. angustifolia).

This product (Polinacea®) was investigated in two distinct groups of volunteers – adults with existing respiratory disorders and healthy adolescents – to determine whether alone or, in the case of the adults with existing respiratory disorders, in combination with the influenza vaccine, it could influence the occurrence of symptoms suggestive of influenza or parainfluenza infection. Results showed a statistically significant tendency for this triple-standardized Echinacea preparation, either alone or in combination with vaccination, to be more efficacious than the vaccination alone, suggesting that this product has the potential to act synergistically with influenza vaccination. The small number of participants precludes any definitive inferences or conclusions in this area.

In a subset of the first pilot trial – the ME group – lab work was conducted for some parameters of immune function. The results observed suggest that the active treatment might have altered immunoglobulin levels, since IgG increased and IgM decreased. White blood cell indices, including monocyte-macrophage and/or neutrophil-mediated response, were not affected by supplementation.

Limitations of this study include the small size of the sample population, a lack of a comparison with other Echinacea preparations, and the failure to monitor aspects of immune performance in all participants. Because of these limitations, our results should be considered preliminary. There were no complaints of side effects in our two pilot studies, and in the first pilot study, there were fewer respiratory complications when the Echinacea preparation was provided either alone or in combination with the vaccine. This excellent tolerability of the extract used, combined with our preliminary results suggesting a potential clinical benefit, provide a rationale to undertake a systematic study on the effects of standardized Echinacea preparations alone or in combination with influenza vaccination in larger trials in order to determine whether these types of products can reduce influenza episodes in individuals at risk (e.g., adolescents, elderly people).

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