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Applications of the Phytomedicine Echinacea purpurea (Purple Coneflower) in Infectious Diseases


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Extracts of Echinacea purpurea (EP, purple coneflower) have been used traditionally in North America for the treatment of various types of infections and wounds, and they have become very popular herbal medicines globally. Recent studies have revealed that certain standardized preparations contain potent and selective antiviral and antimicrobial activities. In addition, they display multiple immune-modulatory activities, comprising stimulation of certain immune functions such as phagocytic activity of macrophages and suppression of the proinflammatory responses of epithelial cells to viruses and bacteria, which are manifested as alterations in secretion of various cytokines and chemokines. These immune modulations result from upregulation or downregulation of the relevant genes and their transcription factors. All these bioactivities can be demonstrated at noncytotoxic concentrations of extract and appear to be due to multiple components rather than the individual chemical compounds that characterize Echinacea extracts. Potential applications of the bioactive extracts may go beyond their traditional uses.
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Hindawi Publishing Corporation
Journal of Biomedicine and Biotechnology
Volume 2012, Article ID 769896, 16 pages
Review A rticle
Applications of the Phytomedicine
Echinacea purpurea
(Purple Coneflower) in Infectious Diseases
James B. Hudson
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3J5
Correspondence should be addressed to James B. Hudson,
Received 26 July 2011; Accepted 29 August 2011
Academic Editor: Munekazu Iinuma
Copyright © 2012 James B. Hudson. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Extracts of Echinacea purpurea (EP, purple coneflower) have been used traditionally in North America for the treatment of
various types of infections and wounds, and they have become very popular herbal medicines globally. Recent studies have
revealed that certain standardized preparations contain potent and selective antiviral and antimicrobial activities. In addition,
they display multiple immune-modulatory activities, comprising stimulation of certain immune functions such as phagocytic
activity of macrophages and suppression of the proinflammatory responses of epithelial cells to v iruses and bacteria, which are
manifested as alterations in secretion of various cytokines and chemokines. These immune modulations result from upregulation
or downregulation of the relevant genes and their tr anscription factors. All these bioactivities can be demonstrated at noncytotoxic
concentrations of extract and appear to be due to multiple components rather than the individual chemical compounds that
characterize Echinacea e xtracts. Potential applications of the bioactive extracts may go beyond their traditional uses.
1. Traditional Uses of
Herbal medicines derived from several species of the
indigenous Echinacea genus were in use throughout the
plains of North America long before the introduction of
European medicines, primarily as treatments for various
infectious diseases and wounds. Nine discrete species were
classified subsequently by botanists, as indicated in Table 1,
although medical records suggest that considerable inter-
change between uses of designated species occurred and
consequently the association of a specific species with
particular treatments has to be viewed with caution [1
3]. Even in recent years there have been revisions in the
taxonomy of the genus [4, 5]. Nevertheless it is generally
agreed that Echinacea purpurea, the purple coneflower, was
widely used by Native peoples and later by the Eclectic
practitioners of North America, possibly because it was so
widespread, and also because it was apparently eective in
a number of diseases. Current herbal preparations, which
have become very popular in North America, Europe, and
elsewhere, have tended to favor this species over the others,
and the majority of the basic scientific studies have focused
on this one. Accordingly, this review is restricted primarily to
discussion of E. purpurea (abbreviated EP), with occasional
reference to alternative species.
The source material for scientific and clinical studies
is usually an aqueous “pressed juice or ethanol tinc-
ture/extract of aerial parts of the dried plant or roots.
The chemical composition diers substantially between such
preparations, at least in terms of the known marker com-
pounds”, such as caeic acid derivatives, alkylamides, and
polysaccharides, all of which have been claimed to contribute
to the medicinal b enefits [57]. However, the uncertainty
in the identity of the principal bioactive compounds has
made interpretation of basic and clinical studies dicult,
and unfortunately the problem has been exacerbated by the
frequent use of uncharacterized source material.
In an attempt to validate some of the traditional uses of
Echinacea, numerous studies have been made recently on the
eects of characterized EP preparations on viruses, bacteria
and other organisms, inflammatory responses, and gene
expression in infected and uninfected human cell cultures,
as well as animal studies. These results are discussed in
following sections. However I have omitted reference to
2 Journal of Biomedicine and Biotechnology
Table 1: Traditional uses of Echinacea (Coneflower) extracts.
Echinacea species Traditional applications
E. purpurea, E. angustifolia,
E. pallida
Respiratory infections: colds and
‘flu, bronchitis, strep throat,
Urinary tract infections: herpes
sores, gonorrhea
Skin disorders: staph infections,
cold sores, ulcers, wounds, burns,
insect bites, eczema, allergies
Others: rheumatoid arthritis
E. paradoxa, E. sanguinea
E. simulata, E. tennesseensis
Not frequently used
Adapted from [1].
studies that used combinations of EP with other herbs, for
reasons explained below (Section 16).
2. Antiviral Activit ies
2.1. Respiratory Virus Infections. Acute respiratory infections
in humans are usually caused by one or more of a group
of well-known viruses, which includes over 100 rhinoviruses
(“common cold” viruses), influenza viruses A and B, parain-
fluenza viruses, corona viruses, respiratory syncytial virus,
and certain adenoviruses [810]. Influenza virus A deserves
special consideration because of its unique capacity for
genetic reassortment between animal and human stra ins and
consequent production of epidemics (Section 2.3 below).
The SARS virus (SARS-HCoV) also merits additional com-
ments, as explained in Section 15. In addition the recent
application of more sensitive molecular detection techniques
has revealed the presence of other viruses, such as metap-
neumoviruses and bocaviruses, which might also be involved
in the generation of respiratory symptoms [10]. However
we do not know if these newly recognized viruses are really
pathogenic or are simply “passengers that eluded previous
diagnostic techniques. Herpes simplex virus type 1 (HSV-
1) also produces oral mucosal infections (“cold sores”), and
these may be accompanied by symptoms reminiscent of
respiratory viruses.
Clearly various families of viruses, with dierent struc-
tures and replication schemes, and consequently bearing dif-
ferent potential molecular targets, are involved in respiratory
symptoms, and many of them are susceptible to Echinacea
extracts, as indicated in Table 2. Among the possible viral
targets are: (i) the virion itself (membrane components); (ii)
cellular attachment or entry; (iii) one or more of the many
stages in virus replication and development, particularly
those that involve virus-specific enzymes; (iv) egress of
progeny virus from infected cells. However, because of
the variety of replication schemes among these viruses the
chances of success for a single therapeutic drug are low,
especially considering that in the majority of respiratory
infections specific virus information is lacking.
Another problem with the specific antiviral target
approach, especially in the case of compounds directed
at specific viral genes or their products, is the inevitable
emergence of virus resistant mutants [14, 15] and their sub-
sequent spread through the community and environment.
The conventional answer to this problem has been to use
combinations of two or more antivira l drugs, with dis-
tinct molecular targets, notwithstanding the likely increase
in undesirable side eects. However, a logical alternative
approach is the use of a noncytotoxic agent that has
the capacity to inhibit many dierent respiratory viruses
simultaneously, and recent evidence indicates that certain
herbal extracts could fulfil l this requirement [1517].
2.2. Causes of Respiratory Symptoms. “Colds, “flu, and
“bronchitis are terms that have been coined to describe
various permutations of common symptoms, supposedly
brought about by the actions of specific viral infections of
the upper respiratory tract. These symptoms may include
such familiar discomforts as sneezing, stuy nose, irritation
of mucous membranes, excess mucus production, sinusitis,
cough, sore throat, malaise, and fever, as well as exacerbation
of asthma and COPD (chronic obstructive pulmonary
disease). In some cases symptoms may spread to include the
lower respiratory tract and lungs and result in bronchiolitis
or pneumonia [16, 1820]. However these symptoms may
not be a direct result of virus replication, which in many cases
is minimal in dierentiated airway tissues [21, 22], but rather
an indirect consequence of virus-induced inflammatory
responses [17, 23].
In respiratory infections, the invading virus initially
encounters epithelial tissues, which are composed largely
of epithelial cells and occasional dendritic cells and
macrophages. These cells respond by means of the various
antimicrobial strategies that make up the innate immune
system, including defense peptides (antimicrobial peptides)
and the secretion of various proinflammatory cytokines and
other mediators of inflammation [2426]. Other molecules
such as kinins are released and are probably responsible for
some of the early symptoms. Rhinoviruses have also been
shown to induce kinin gene expression [27], although this
eect is more likely a delayed e ect of virus infection. In
response to all these mediators phagocytic cells and various
types of inflammatory cell may then be attr acted to the site of
infection [26]. In addition the redox balance of the cells may
be adversely aected, either by the virus infection itself or as
a consequence of the proinflammatory response [28].
Since most of the symptoms reflect this common non-
specific host response to infecting agents, rather than to
the direct cytolytic or cytopathic eects of a specific virus
17], then a more rational therapeutic approach would
be the application of anti-inflammatory agents, especially if
the intention of the therapy is to ameliorate symptoms. If a
potential safe anti-inflammatory agent also contains multiple
antiviral activities, then this would provide a bonus. Several
herbal extracts have been shown to possess a combination of
bioactivities that could be useful in the control of respiratory
infections [17, 29, 30], and these Echinacea extracts have
Journal of Biomedicine and Biotechnology 3
become very popular, although, because of the variation in
their chemical composition (as mentioned in Section 1), not
all of them are necessarily beneficial.
2.3. Influenza Virus Type A. Influenza viruses are ubiquitous
and produce significant annual morbidity and mortality
throughout the world, with potentially devastating con-
sequences for human and animal health, and the global
economy [31, 32]. Thereare three types of influenza virus, A,
B, and C, the latter two being confined mainly to humans,
in which they produce relatively mild seasonal outbreaks.
However the greatest impact derives from Influenza A virus,
which has been associated with several well-known human
pandemics during the last century and an increasing number
of epidemics (epizootics) in domestic birds [3134]. It is
believed that influenza A virus originated in wild birds,
possibly waterfowl such as ducks and geese and that these
birds act as reservoirs and vectors for the many known
subtypes (strains) of influenza A virus [35].
The classical symptoms of human influenza include
cough, malaise, and fever, often accompanied by sore
throat, nasal obstruction, and sputum production, which
resolve spontaneously in most healthy individuals, although
immune compromised and elderly individuals tend to be
more vulnerable. Complications may include bronchitis
and pneumonia, and exacerbation of asthma, and chronic
obstructive pulmonary disease (COPD) [16, 18, 20].
More serious disease in healthy individuals, especially
during pandemics, is often accompanied by excessive over-
reaction of the innate immune response with the secretion of
dangerous levels of cytokines (“cytokine storms”) and other
inflammatory mediators [3234]. Also the importance of
concurrent bacterial infection cannot be overlooked, since
this may lead to more serious outcomes [36]. Thus an
ideal control agent should be able to prevent or reduce the
replication and spread of the virus, as well as any potentially
pathogenic bacterial infection, and also counteract the
overproduction of inflammatory mediators.
Vaccines are generally advocated for routine application
during each influenza seasonal outbreak, based on the
prevailing strain of the previous season; but because of the
unpredictable nature of influenza epidemics one cannot be
sure of the success of any vaccine, and several researchers
have questioned the wisdom of widespread vaccination [15,
31, 37, 38].
Numerous antiv iral drugs for use in infected patients
have been tested experimentally, in animal models and in
humans, but none has proven satisfactory [30, 39 ]. The
most recent synthetic compounds are the neuraminidase
inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza),
but drug-resistant strains of human and avian Influenza
viruses have been documented with increasing frequency
[40, 41].
2.4. Antiv iral Activities of Echinacea Purpurea (EP). Early
studies showed that only certain Echinacea extr acts possessed
significant antiviral activity. E. purpurea (EP) aerial parts a nd
roots contained potent antiviral activities (virucidal) against
influenza virus, herpes simplex virus, and coronavirus, and
these were distributed among more than one solvent derived
fraction, probably reflecting the presence of more than
one antiv iral compound [11, 12]. However there was no
correlation between antiviral activit y and composition of
the recognized marker compounds, that is, caeic acids,
polysaccharides, and alkylamides, and in fact a purified
polysaccharide fraction from EP possessed no significant
activity, while cichoric acid and several caeic acid deriva-
tives showed only weak to moderate activity, insucient to
account for the potent activities of EP [42]. In addition
the antiviral activ ity of commercial ethanol tinctures from
EP can remain stable for at least several years at ambient
temperatures, which would seem to rule out many potential
candidate bioactive compounds. Furthermore some, but not
all, of the antiviral activities were due to photosensitizers,
which again limits the number of prospective candidates
[12, 43].
Recent studies with the standardized preparation Echi-
naforce (EF, comprising ethanol extracts of E. purpurea, 95%
aerial parts plus 5% roots) showed that this preparation
was a very potent virucidal agent against several viruses
with membranes, as indicated in Table 2
. In a ddition to
HSV-1 and respiratory syncytial virus, all tested human
and avian strains of influenza A virus, as well as influenza
Bvirus,weresusceptible[13, 44]. In addition rhinovirus
and feline calicivirus were also equally susceptible at the
relatively high concentrations of EF recommended for oral
consumption [45]. Thus EF at 1 : 10 dilution (equivalent
to 1.6 mg/mL dry weight/volume) was capable of killing at
least 10
infectious viruses by direct contact. Adenoviruses
however were resistant.
eective against intra cellular virus [13, 44]. Consequently
viru s already present within a cell could be refractory to
the inhibitory eect of EP, whereas virus particles shed into
the extracellular fluids should be vulnerable. Therefore EP
can act during initial contact with the virus, that is, at the
inception of infection and also during transmission of virus
from infected cells.
Additional experiments showed that continuous passage
of influenza A virus in cell cultures in the presence of EP did
not result in the emergence of resistant stra ins, whereas pas-
sage of the virus through successive cultures in the presence
of Tamiflu rapidly generated Tamiflu resistance. Furthermore
Tamiflu-resistant virus remained fully susceptible to EP [13].
Therefore continuous usage of EP in the population would be
less likely to generate resistant strains of virus than Tamiflu
or other anti-influenza compounds currently in the market.
It was shown by hemagglutination assays that EP inhib-
ited the receptor-binding activity of influenza A viruses, over
a range of EP concentrations, suggesting that EP interfered
with viral entry into the cells, thus eectively rendering the
virus noninfectious [13]. EP also inhibited neuraminidase
activity in vitro (unpublished results), suggesting that the
active compounds could block influenza virus entry and
spread by acting on at least two virion targets. However, the
susceptibility of other viruses, which do not rely on HA or
4 Journal of Biomedicine and Biotechnology
Table 2: Antiviral activities of EP at noncytotoxic concentrations.
virus Relevant properties
Susceptible to EPethanol
extracts (+ or -)
Susceptible to EP aqueous
extracts (+ or -)
rhinoviruses ss RNA, no membrane + only at high conc. + only at high conc.
Influenza viruses
segmented RNA, + membrane & 2 target
virion proteins (HA, NA)
Respiratory syncytial virus ss RNA, + membrane & fusion protein + nt
Coronavirus ss RNA + membrane + (mouse virus) nt
Calicivirus ss RNA, no membrane + high conc. + high conc.
Poliovirus ss RNA, no membrane - -
Herpesviruses dsDNA+membrane + +
Data from [1113].
NA functions, to EP, indicates that there must be additional
molecular targets.
3. Effects of EP on Virus-Infected Cells:
Involvement of Cytokines and Chemokines
Rhinovirus-infected human bronchial and lung epithelial
cells were used to study the eects of EP on cellular gene
expression and secretion of cy tokines and chemokines, prin-
cipal mediators of inflammatory responses. Rhinoviruses
stimulated the secretion of many dierent cytokines [46, 47],
including the proinflammatory IL-1, IL-6, IL-8, and TNFα,
which are known to be collectively involved in many of the
symptoms common to respiratory infections, such as sneez-
ing, fever, sore throat, nasal discharges, and inflammation in
various respiratory tissues. Several EP preparations were able
to completely or partly reverse this stimulation [4850]. EP
could be added before or after virus infection, with similar
success, and also the results were not aected by virus dose
or the time of exposure to EP [49].
It is noteworthy that RV14 and RV1A, which are known
to use distinct cellular receptors (ICAM-1 and LDL, resp.),
both stimulate cytokine secretion that is reversed by EP,
suggesting the involvement of multiple signaling pathways.
This concept was supported by the demonstration that many
transcription factors ( TF’s) known to be associated with
cytokines and chemokines were also stimulated by RV14, and
these TF’s were modulated by EP treatment [50, 51].
Other viruses, including HSV-1, influenza A virus,
adenovirus type 3 and 11, and respiratory syncytial virus,
stimulated the secretion of pro-inflammatory cytokines, and
in each case the stimulation was reversed by EF (Ta ble 3,
and [44]). However only live infectious viruses were able
to do this, for infection by equivalent doses of ultraviolet-
inactivated viruses failed to elicit the responses. This suggests
that the virus may have to enter the cells and undergo
some degree of gene expression in order to stimulate the
cytokine expression or secretion. It is also interesting that
viruses such as adenoviruses, which are not vulnerable to
direct attack by Echinacea, but could nevertheless stimulate
cytokine secretion, were still susceptible to cytokine reversal.
In a more recent study with influenza A-infected mouse
macrophage-like cells, the v iral induced production of
cytokines and chemokines was also suppressed to various
degrees by EP extra cts and some of their constituent
alkylamides (details below).
Several conclusions can be derived from these results.
Probably the most important is that we could not corre-
late cytokine inhibitory eec ts, that is, anti-inflammatory
properties, with specific individual compounds or groups of
marker compounds, namely, alkylamides, polysaccharides,
and caeic acid derivatives. In the case of EP, all the fractions
derived from roots, leaves plus stems, and flowers, were
anti-inflammatory according to IL-6 and IL-8 measurements
[52]. Numerous viral and bac terial infections, as well
as wounds, result in substantial stimulation in levels of
proinflammatory cytokines, especially IL-6 and IL-8, which
are consequently considered to represent useful markers of
an inflammatory condition [23, 29]. Thus any compound
or herbal extr act that inhibits or reverses this elevation in
IL-6/8 and so forth, could be considered as a potential
anti-inflammatory agent. Consequently many preparations
derived from roots or aerial parts of EP would be expected to
possess anti-inflammatory properties.
4. Mucin Secret ion
Secretion of excessive mucus is one of the more annoying
symptoms of colds and other respirator y infections and
occurs frequently in chronic pulmonary infections. Many
pharmaceuticals have been designed to relieve this feature of
an infection, usually with the accompaniment of undesirable
side eects.
Mucins, the products of at least 18 mucin genes in
humans, are highly glycosylated macromolecules that con-
stitute part of the innate defense system against respiratory
pathogens [53], But in some chronic conditions, and in
response to certain airway infec tions such as rhinovirus [54],
one or more genes may be induced to hypersecrete mucins.
In studies on bronchial epithelial cells in culture, and in
organotypic bronchial tissue cultures, rhinovirus induced
the secretion of excess MUC5A, the dominant respiratory
mucin, and EP reversed this secretion [55], suggesting that
this could be an additional benefit of EP treatment. Tabl e 4
shows a representative result.
Journal of Biomedicine and Biotechnology 5
Table 3: Cytokines/chemokines induced by viruses (+) and
reversed by EP.
cytokine RV1A RV14 FluV RSV Ad 3
IL-1a + + + + +
IL-5 + +
IL-6 + + + + +
IL8 (CXCL-8) + + + + +
TNFα +++++
GROα +++
CCL-3 + +
CCL-4 + +
Adapted from [44]. RV: rhinovirus (1A/14); FluV: influenza virus
(H1N1/H3N2); RSV: respiratory syncytial virus; Ad 3: adenovirus type 3.
5. 3-D Tissues of Human Airway Epithelium
It is important that the cell culture models used to
evaluate anti-infectious agents reflect conditions in vivo
as far as possible [56]. This condition was confirmed for
EP by means of a commercial source of normal human
airway epithelial tissue (EpiAirway tissue, a 3-D organotypic
model), which could be propagated ex v ivo under defined
conditions such that tissue architecture and dierentiation
patterns were preserved, according to standard histological
examination [57]. Under these conditions the eects of
rhinovirus infection, and EP, on various parameters of
tissue integr ity and cytokine induc tion were evaluated [55].
Individual replicate tissue samples, maintained as inserts in
culture for three days or three weeks, were infected with
rhinovirus type 1A (RV1A), EP alone, a combination of the
two, or medium only. None of the treatments aected the
histological appearance or integrity of the tissues, al l of which
maintained a high level of cell viability and preservation of
cilia, with the exception of the conspicuous virus-induced
mucopolysaccharide inclusions in the goblet cells. There was
no evidence of virus replication, although the RV infected
tissues secreted substantial amounts of the proinflammatory
cytokines IL-6 and IL-8, and this response was reversed by EF
treatment (Tab le 5). The goblet cells also appeared normal
and free of inclusions in the EP-treated tissues. Therefore
these results confirmed the findings derived from studies of
bronchial and lung epithelial cell lines (above), namely, that
RV infection resulted in a substantial inflammatory response
and mucin secretion in the absence of virus replication.
6. Effects of EP on Gene Expression in
Rhinovirus-Infected Cells
Gene expression in human bronchial cells was analyzed by
means of DNA microarrays, following treatment by one of
two EP preparations, an aqueous extract and an ethanol
extract, with or without infection by rhinovirus type 14 [58,
59]. Both extracts influenced the expression of many genes,
including cytokine genes, although the pattern of expression
was dierent for the two extracts. In addition the virus itself
induced numerous changes, mostly increases in expression,
Table 4: Mucin secretion in human epithelial cell cultures.
Treatment Ratio, treatment/control
None (control) 1.00
Echinacea (EP) only 0.76
Rhinovirus (RV1A) infection 2.18
Echinacea (EP) + RV1A 0.64
Bronchial epithelial cell cultures (BEAS-2B) were treated with combinations
of EP and rhinovirus RV1A, as indicated, and supernatants were assayed for
secreted MUC5A by ELISA (details in [55]).
and the extracts tended to decrease (i.e., restore to normal
levels) these expression levels. Further analysis of the eects
revealed that some of the changes in cytokine expression
were interconnected through a specific transcription factor,
C/EBPb (CAAT/enhancerbinding protein b, [59]). Since
numerous transcription factors were known to be aected by
EP extract in this same cell-virus system [50], it is tempting
to conclude that many gene expression eects of Echinacea
extracts could be due to changes in expression or activation
status of multiple transcription factors. This in turn could be
brought about by interaction with surf ace receptors or their
intracellular modulators.
Analyses of IFNα (interferon alpha) gene expression, by
DNA microarray analysis and PCR assays, revealed only a few
changes in cells treated by dierent EP extracts, in uninfected
bronchial epithelial cells, or in rhinovirus-infected cells,
although certain interferon stimulated genes (ISG’s) were
upregulated by the virus and downregulated by the EP
extracts [59]. Interferon bioassays in bronchial cells failed to
detect IFN, in contrast to cells stimulated by the known IFN
inducer poly I : C (Vimalanathan and Hudson, unpublished
data). Negative findings were also reported recently in a
mouse macrophage cell line infected with HSV-1 [60], from
which the authors concluded that EP induced little if any IFN
alpha or beta, and consequently antiviral eects of EP are not
likely to involve the interferon system.
7. Antibacterial Activities
Several potentially pathogenic bacteria have the capacity
to cause respiratory symptoms, resulting from initial inter-
actions with epithelial cells of the oral and nasal mucosa
and various parts of the lung. General features of infection
by these organisms include proliferation and spread of
the bacteria with resultant cellular damage, often aided by
products of bacterial v irulence genes, and the induction
of excessive proinflammatory cytokines, which c an lead to
chronic inflammation. A herbal medicine with bactericidal
and anti-inflammatory properties could provide benefits
to individuals suering from respiratory symptoms, and
certain preparations of EP possess these activities, in addition
to their antiviral activities described above. Results are
summarized in Table 6 .
Streptococcus pyogenes (Group A streptococcus, or GAS)
is responsible for widespread infections, ranging from hun-
dreds of millions of relatively mild cases of pharyngitis
6 Journal of Biomedicine and Biotechnology
globally, to more severe toxic shock syndromes and necrotiz-
ing fasciitis (“flesh-eating disease”), the more severe symp-
toms being ascribed to inflammatory cytokines (“cytokine
storms”). In addition several Streptococcal gene products or
virulence factors have been described which aid the bacteria
in persistence in oral epithelia and saliva and dissemination
to other tissues [6366]. Consequently the dual actions of EP
in killing the bacteria and reversing their proinflammatory
activities could be a significant aid in combating such
Hemophilus influenzae is part of the norm al naso-
pharyngeal flora. Recently additional pathogenic strains have
been associated with otitis media, chronic bronchitis, and
pneumonia. Initial interaction with epithelial cells can result
in proinflammatory cytokine secretion, via toll receptors and
other mediators [66, 67]. EP can kill this organism readily
and also inhibit the cytokine induction in bronchial epithelial
cells (Table 6).
Legionella pneumophila, associated w ith Legionnaires
disease and sometimes more severe cases of pneumonia,
is widely distributed in water a nd soil, from which the
organism can be inhaled as an aerosol and once inside alve-
olar macrophages localizes in a relatively resistant vacuole,
in which it replicates [68, 69]. The organism is however
very sensitive to EP, and its induction of proinflammatory
cytokines is inhibited by EP treatment (Ta ble 6).
Staphylococcus aureus has long been recognized as part
of the normal skin flora, but Methicillin-resistant (MRSA)
strains have been associated in recent years with increased
frequency of hospital-acquired infections, resulting in severe
pneumonia [70, 71]. Preparations of EP had relatively
little eect on growth of MRSA or MSSA (methicillin
sensitive S. aureus)butwereveryeective in inhibiting
the proinflammatory response to the bacteria, indicating at
least partial benefits in counteracting the detrimental eects
of MRSA infection. Klebsiella pneumoniae, often associated
with antibiotic resistant pneumonia, was also relatively resis-
tant to the bactericidal eects of EP, as were Mycobacterium
smegmatis and several other bacterial opportunists [62].
Several conclusions were drawn from these results: (i)
EP and other Echinacea extracts were selective in their
antibacterial activ ities; (ii) dierent organisms showed sig-
nificant dierences in their patterns of sensitivity; (iii)
there were no correlations between chemical composition
of extracts, in terms of known marker compounds, and
their corresponding antibacterial activities; (iv) dierent
preparations of Echinacea showed markedly dierent eects
on bacteria, indicating that EP has distinct mechanisms of
action against each bacterium; (v) in general EP c an reverse
the stimulation of proinflammatory cytokines regardless of
the inducing bacterium or virus.
In addition to the studies with live bacteria, several
groups have examined the eects of EP on the stimulation
of inflammatory mediators by bacterial lipopolysaccharide
(LPS usually derived from Escherichia coli)invarioushuman
and mouse cell cultures (see below, Section 12). Such models
can serve as useful tests for anti-inflammatory agents [23,
29], although they do not necessarily represent live bacteria.
These studies together indicate that EP is e
ectively a general
Table 5: Eects of EP on cytokines/mucin in 3-D tissues (ratio,
Treatment IL-6 IL-8 MUC5A
EP 0.7 1.5 0.82
Rhinovirus 3.1 22.0 2.0
EP + rhinovirus 0.5 2.0 0.76
Data from [55].
anti-inflammatory agent and should be capable of ameliorat-
ing many of the symptoms of respiratory infections.
8. Coinfections with Viruses and Bacteria
Many authors have commented on the importance of
coinfections of the airways between a respiratory virus and
bacterial opportunists, and the possible enhancement of
pulmonary diseases [36]. This has already been alluded to
above, but a number of interesting studies have suggested
possible mechanisms. Rhinoviruses, respiratory syncytial
virus, and influenza virus, all altered signaling pathways in
cultured epithelial cells, leading to cell membrane changes,
including enhancement of attachment of certain bacteria,
such as H. influenzae and S. pneumoniae, and resulting in
cytopathic eects and possible colonization [7275]. The
reverse process was also demonstrated; prior infection of
epithelial cells with H. influenzae increased the level of
ICAM-1 receptors and resulted in enhanced rhinovirus
infection [76]. Since EP can inact ivate these viruses and
bacteria on contact, as well as inhibiting their induction
of proinflammatory cytokines, it is conceivable that such
coinfections could be halted by EP oral administration in the
form of tinctures or sprays.
9. Skin Infections
9.1. Herpes Simplex Viruses. Many skin infections are caused
by viruses and microorganisms, and some of these could be
amenable to topical treatment with EP. Herpes simplex virus
types 1 and 2 (HSV-1/2) are common infections of oral and
genital mucosa (“cold sores” and genital sores”) and may
become chronic infections with painful recurrent eruptions
of the skin. Keratitis, an infection of the corneal epithelium
and stromal tissue, which may also be recurrent, is a major
cause of blindness. Fortunately most of these infections
are accessible to topical agents, and not surprisingly many
antiviral drugs have been marketed for their control, with
variable success; but since most of these were designed to
target viral genes, then emergence of resistant mutants is
always a threat. However many plant extracts have been
evaluated as anti-HSV agents [77, 78], and some of these
have shown promising results. Several EP preparations
showed potent virucidal activity against HSV, and these
results have already been summarized in Section 2.1 above,
in connection with respiratory viruses. The advantages of
EP are its broad spectrum of activity, which minimizes the
chances of resistant mutants arising, its high potency, and its
relative lack of cytotoxicity.
Journal of Biomedicine and Biotechnology 7
9.2. Acne. Acne vulgaris is a multifactor ial chronic disorder
of the pilosebaceous follicles of the skin. Propionibacterium
acnes, the dominant microbe in the sebaceous glandular
regions, and inflammation, possibly initiated by this bac-
of the disease, although other factors also appear to be
involved, such as hormones and host nutritional status [79].
One explanation for the chronic nature of the disease is
that the P. acne s induces the production of proinflammatory
cytokines and chemokines, as well as other inflammatory
mediators, which attrac t leukocytes to the site of infection
and thereby set up a cascade of inflammatory responses,
which also involve production of reactive oxygen species
and other radicals, all of which in combination lead to the
development of the acne lesion [79, 80].
Conventional therapy targets the development of the
lesions, by means of retinoic acid analogues and other
compounds and antibiotics directed against the bacterium
[80]. Needless to say that the continued application of
antibiotics entails the risk of resistant bacteria emerging. As
an alternative approach, several recent reports h ave indicated
the possibility of using plant extracts to counter the growth
of the bacteria and/or the inflammatory response, although
these have yet to be evaluated in vivo (e.g., [81]).
The organism itself, including labor atory and clinical
isolates, was readily inactivated by dilutions of EP well below
the normal recommended dose for topical treatment or for
oral consumption in the control of colds and flu symptoms.
Furthermore, the bacterial induction of proinflammatory
cytokines, evident in three human cell lines examined
(bronchial epithelial, lung epithelial, and skin fibroblasts)
was also inhibited by EP, which suggests that this extra ct
could oer dual benefits to acne patients [82]. Results
are summarized in Tabl e 7. The bacterial-induced cy tokines
included IL-6 and IL-8 (CXCL8), and to a lesser extent
TNFα, which are hallmarks of inflammatory responses and
would be expected to lead to influx of various inflammatory
leukocytes. In addition the secretion of GROα normally
results in attraction of monocytes. Such a combination of
cytokines could well explain the production of inflammation
at the site of the infection; consequently an agent capable of
safely reversing this eect should be beneficial to the patient.
9.3. Fungi. Fungi are the causative agents of numerous acute
and chronic infections of the skin in many par ts of the
body and are often inaccessible to immunological attack. A
limited number of studies have been reported on antifungal
activity of various Echinacea extracts, including some EP
extracts, against Candida species and some dermatophytes,
but these were essentially qualitative by design and merely
indicated that certain extracts could inhibit growth of
some fungi [83, 84]. Since EP is formulated for oral and
superficial applications, a more comprehensive evaluation of
their fungistatic and fung icidal ac tivities could support and
validate some of the traditional uses and anecdotal reports
of success in controlling chronic fungal infections of the skin
10. Other Organisms
10.1. Clostridium Dicile. C. dicile is a Gram positive
spore-forming gut anaerobe, which has been associated
increasingly in recent years with epidemics of diarrhea
(Clostridium dicile-associated diarr hea, CDAD) and pseu-
domembranous colitis, especially in health care institutions
where patients may be subjected to chronic administration of
antibiotics with resulting disruption of the normal balance of
gut flora [85, 86]. Certain preparations of EP are capable of
killing the organism [61], as shown in Table 8. This suggests
that oral consumption of appropriate extracts, and possibly
some teas made from EP, could be beneficial in infected
patients. It has been reported that EP supplementation to
the diet can apparently cause changes in gut bacterial flora
[87], but it is not clear how significant such changes are and
whether they are beneficial or not.
10.2. Parasites. Leishmaniasis and trypanosomiasis are dis-
eases caused by protozoans Leishmania and Trypanosoma
species belonging to the trypanosomatidae family. Leish-
mania species are mainly transmitted by the bite of an
infected female phlebotomine sandfly [88]. Trypanosoma
species are transmitted to humans by the bite of an infected
tsetse fly (Glossina Genus), causing sleeping sickness, or
an infected Assassin bug (sub-family Triatominae), causing
Chagas disease in humans.
Both parasites cause widespread disease, with hundreds
of thousands of new cases each year. Although dru gs are
available for the treatment of dierent stages of the diseases,
they are frequently associated with severe side eects [88, 89].
However some recent studies have examined antiparasitic
properties of several plant extracts, with promising results
[89, 90].
Three dierentpreparationsofEP,oneanethanolextract
and the others aqueous extracts of aerial plant parts, were
evaluated for their ability to inhibit growth of the organisms
in vitro and antiinflammatory activity [90].
All three EP preparations exhibited dose-dependent anti-
leishmanial and trypanocidal activ ities after 24, 48, and
72 h incubation, although their relative potencies varied
somewhat between extracts and target species. In general the
ethanol extract was the most eective.
It may dier between species, as it does for bacterial species
(Section 8, above). Microscopic observations on the parasites
indicated that EP slowed or eliminated their motility and
caused cell rounding at high EP concentrations.
L. donovani also showed proinflammatory activity by
stimulating the secretion of IL-6 and IL-8 (CXCL8) in two
dierent human cell lines a bronchial epithelial line and
a skin fibroblast line, similar to the stimulation shown in
these cell lines by a variety of other viral and bacterial
pathogens (as described above). In both cell typ es, the
selected EP ethanol extra ct inhibited these Leishmania-
induced responses (Tabl e 9). Thus certain Echinacea prepa-
rations are capable of controlling growth of these parasites,
and can inhibit the inflammatory activity induced by them.
8 Journal of Biomedicine and Biotechnology
Table 6: Antimicrobial eects of EP.
Species Relative microbicidal activity of EP ( to ++) Anti-inflammatory response by EP (+ or )
Streptococcus pyogenes ++ +
Hemophilus influenzae ++ +
Legionella pneumophila ++ +
Staphylococcus aureus +/
Klebsiella pneumoniae +/
Propionibacterium acnes ++ +
Mycobacterium smegmatis ++
Clostridium dicile ++ +
Candida albicans +nt
Leishmania donovani ++
Trypanosoma brucei +nt
Bacterial lipopolysaccharide (LPS) n/a +
Data from [61, 62]. nt = not tested; n/a = not applicable.
Table 7: EP reversal of P. a cnes induced cytokines/chemokines.
Cytokine/chemokine Ratio, P. a cnes/control
Ratio, P. a cne s
+ EP/control
IL-6 7.0 2.7
IL-8 (CXCL8) 3.0 0.35
GROα 1.9 0.56
TNFα 1.2 0.52
Data from [82].
11. Antioxidant Properties
Many plant extracts have been shown to contain antioxidant
properties, according to several standard tests, and phenolic
components have often been incriminated [5, 29, 84, 91].
In addition to the generally accepted nutritional and health
benefits of adding antioxidants to the diet, various acute
and chronic infections have been associated with nega-
tive eects on the intracellular redox balance, including
decreases in reduced glutathione and other important cellu-
lar antioxidants, which could have adverse eects on cellular
metabolism [28].
Several reports have demonstrated the anti-oxidant
property of EP preparations [84, 92]. Therefore supplemen-
tation with EP during infections could provide additional
host protection by restoring the normal redox status.
12. Effects of EP on Immune Cell Functions
Several studies have reported the eects of Echinacea prepa-
rations on cellular gene expression in uninfected human cells
relevant to the immune system. Changes in NK cells and
cell surface antigens were described for blood cells taken
from humans treated with EP [93, 94]. Randolph et al.
[95] described changes in levels of expression (in terms of
mRNAs and proteins) of se veral cytokine genes in human
blood samples taken at dierent times after treatment with a
commercial Echinacea product, and Brovelli et al. [96]found
that the expression of several cytokine genes in cultured
human monocytes was influenced by the nature of the
Echinacea preparation (stage of development and plant part
used), presumably a reflection of their dierent chemical
Wang et al. [97] described the eects of a butanol
fraction, derived from aerial parts of E. purpurea,ongene
expression of immune-related molecules in human dendritic
cells, which are part of the adaptive immune response.
Many dendritic cell genes were aected, either upregulated
or downregulated. Modulation of several cytokines by EP
extract was also reported for cultured mouse dendritic cells
[98]. None of these studies included infected cells, but they
clearlyconrmedthatEPproducesmultiplegeneeects in
immune cells.
Many groups during the last 20 years have investi-
gated the eects of Echinacea preparations on immune
functions in cell cultures of mouse origin. In gen-
eral, incubation of peritoneal, alveolar, or spleen mono-
cyte/macrophage/lymphocy te preparations with EP resulted
in stimulation of phagocytosis and cytokine secretion
(reviewed in [5, 6]). This was in contrast to the stud-
ies described above for infected airway epithelial cells
and fibroblasts, in which EP generally acted as an anti-
inflammatory agent, via numerous changes in gene expres-
sion. In studies with partially purified EP polysaccharides
(derived from in vitro EP plant cultures), stimulation of
phagocytic activity in macrophages was also observed [99,
100], whereas isolated Echinacea alkylamides, individually
or in groups, invariably displayed immune suppression in
various cultured cells [101105].
Unfortunately the earlier studies gave rise to a popular
belief that Echinacea acted as a general “immune stimulant”
or “immune booster”, statements that persist today on
many commercial labels and web site descr iptions. More
recent studies however refer more appropriately to immune
modulation rather than generalized immune stimulation
(e.g., [47, 101105]). Thus the net result of interactions
between EP and cells in vivo will likely be influenced by the
composition of the extract a nd the nature and location of the
cell type.
Journal of Biomedicine and Biotechnology 9
Table 8: Eect of EP on Clost ridium dicile.
EP extract
C. dicile
(cfu/2.5 μL)
None 1.5 × 10
EP ethanol (moderate
alkylamides; no polysaccharide)
<10 >3
EP aqueous (+ polysaccharide; no
× 10
Data from [61].
Rininger et al. made a dierent series of observations
[106]. They reported that several preparations of EP showed
minimal eects on production of cytokines in mouse
cultures, unless the extracts were first exposed to a simulated
gastric and intestinal digestion protocol, whereupon they
acquired the abilit y to stimulate cytokine secretion. This
result is clearly relevant to normal consumption of Echinacea,
but remains unexplained.
LPS (bacterial lipopolysaccharide) treatment by stimulating
the production of the inflammatory mediator nitric oxide,
and EP was able to inhibit this eect [92], in accordance
with the anticytokine eects described above. In our pre-
liminary studies (Sharma and Hudson, unpublished results)
rhinovirus also stimulated NO production in these same
cells, and EP reversed this eect. Thus although potential
phagocytic cells can be stimulated by EP, similar cells that
have already been stimulated by LPS (or possibly by live
bacteria) are inhibited by EP, indicating the tendency of EP
to restore normal immune functions.
13. Studies in Rodents
EP-treated rats were assessed for spleen and lung
macrophage-related func tions, including phagocytic activity
and cytokine stimulation, both of which were stimulated in
the treated animals [107], in agreement with the studies on
mouse cells cultured in vitro.
In the studies with EP polysaccharides derived from
plant cultures, treated normal and immunosuppressed mice
could be protected from a lethal dose of either Listeria
monocytogenes or Candida albicans, apparently as a result
of reduced titers of the organisms in target tissues [108].
A similar beneficial eect of standard EP extract was also
observed in a recent study in which mice were infec ted
with Listeria monocytogenes [104]. Whether the protection
in these cases was due to enhanced phagocytic activity
and clearance of the organisms in various tissues, or to
direct contact of EP components with the organisms, or a
combination of these and other factors, is not clear from
these studies.
A recent report described the successful use of a
polysaccharide-enriched aerial EP extract in controlling the
course of influenza virus A infection (a well characterized
H1N1 strain) in mice. There was no apparent eect on
lung virus titers, but there were significant eects on
various cytokine levels in lungs and sera [109]. The authors
concluded that the benefits of EP treatment resulted from
modulation of inflammatory cytokines, rather than direct
antiviral activity, and this concurs with the studies indicating
anti-inflammatory properties of EP. Thus EP could still be
beneficial in systemic infections in which EP components are
unlikely to make direct contact with the virus.
Miller and colleagues [110112]havemadeseveral
studies of the eects of dietary EP extract on the aging and
survival of mice. Several parameters of growth indicated
possible benefits of the EP diet, and a noteworthy positive
eect was the lifelong stimulation of NK cell activity and
function, which could theoretically help the animals deal
with infectious diseases.
14. Veterinary Applications
Most domestic animals, including pets, livestock, and fish,
require treatment at some point in their lives for viral and
microbial diseases, and the causative organisms are usually
analogous to the corresponding human counterparts that
have already been discussed, for example, avian influenza
viruses, animal herpes viruses, various respiratory viruses
and bacteria, and many fungal and parasitic infections.
Consequently some of them should be responsive to Echi-
nacea treatment, either as direct antivirals, antimicrobials,
or as an anti-inflammatory agent. In addition some of
these organisms, especially bacteria such as Salmonella
and Campylobacter species, are also important sources of
contaminated foods. Furthermore some commentators have
pointed out the need to e valuate herbal preparations as
replacements for at least part of the antibiotic onslaught that
farmed animals often receive.
Certain herbs, including Echinacea, have a modern
tradition of veterinary applications [113, 114], in North
America and Europe, a nd although relatively few reports
have described basic studies analogous to those described
for human diseases, or even controlled trials in animals,
invariably the treatments were concluded to be safe and free
of significant side eects. This conclusion is also supported
by the studies in mice and rats described in the previous
section, in which toxic eects were not observed.
In regard to infections, a study in chicks infected with the
protozoan parasite Coccidia concluded that dietary supple-
mentation with EP root extract significantly decreased lesion
scores and improved the health of the animals, in comparison
with animals raised on a normal diet [115], although
immune parameters were not measured; consequently it is
not clear if the eect of EP was directed against the parasite
itself or on the immune system. Nevertheless an eective
treatment for coccidiosis would be welcome in the poultry
On the other hand, in a study in young pigs [116],
dietary EP was found to oer no protection against the
porcine reproductive and respiratory syndrome virus (PRRS
virus). Since this virus is a member of the arterivirus family
(related to coronaviruses) and possesses a membrane, it
would be expected to be susceptible to direct contact with EP.
However the systemic nature of the infection could render it
10 Journal of Biomedicine and Biotechnology
Table 9: EectofEPonLeishmania-induced secretion of cytokines.
Cells Treatment IL-6 (pg/mL) IL-8 (pg/mL )
Bronchial epithelial cells
None, control 19.8 42.8
+ EP 29.2 45.7
+Ld(Leishmania donovani) 63.1 147.5
+ Ld + EP 25.8 18.1
Human skin broblasts
None, control 29.8 62.0
+ EP 38.2 74.4
+ Ld 207.8 320.0
+ Ld + EP 9.6 42.8
Data from [90], (standard devi ations removed for simplicity).
inaccessible to dietary Echinacea components. Alternatively,
the treatment protocol might have been inadequate.
In addition to controlling infections in domestic animals,
herbal preparations have been advocated for such things as
immune stimulation, growth promotion, and performance
enhancement. Studies carried out in uninfec ted horses [117]
and fish (Tilapia, [118]) suggest possibilities for Echinacea
preparations. Again safety was not considered a problem
for the animals. Fish, like other farmed animals, are always
potentially vulnerable to v iral and microbial infections, espe-
cially under conditions of stress; consequently alternative
treatments to synthetic antimicrobials could be useful.
15. Emerging Infections: The Example of Severe
Acute Respiratory Syndrome (SARS)
In case we needed to be reminded of the unpredictable nature
of microbial epidemiology, the SARS epidemic erupted in
China in late 2002 and quickly spread to many other
countries over the next year and a half, resulting in more
than 8,000 seriously infected individuals, of whom nearly
10% died. The epidemic was ocially recorded as the first
pandemic of the 21st century. As a result of emergency global
public health measures the disease was halted and appears
to have been controlled, although continued vigilance is
necessary in case the causative virus returns [119].
The novel coronavirus responsible (SARS CoV), believed
to be of animal origin, was isolated and its genome quickly
sequenced [119]. However no satisfactory antiviral therapy
was or is available. A study on autopsy lung tissues revealed
that viral nucleoprotein and RNA were present mainly in
alveolar epithelial cells, the probable initial site of vir us
replication, and to a lesser extent in macrophages, which
could be the mode of systemic transmission [120]. A more
recent review summarized studies on SARS CoV infection
in cell cultures and emphasized the role of innate immune
responses to the virus infection [121]. This virus, like
other coronaviruses and other respiratory viruses, stimulates
inflammatory cytokine secretion, although coronaviruses
generally do not induce antiviral interferon. Thus mod-
ulation of cytokines and evasion of the innate immune
defences could be important contributors to SARS virus
pathology. Therefore a herbal preparation like EP, with anti-
inflammatory and virucidal properties, could be useful if the
SARS were to return.
16. Standardization and Herb Mixtures
The need for standardization of EP has already been stressed
in this paper, and a few studies h ave reinforced the concept
of variation among dierent preparations from dierent
suppliers [45, 106, 122]. This is a common problem with
herbs, since the exact chemical composition can vary with
dierent parts of a plant, the age and season of harvest,
and the exact method of extraction [6, 7, 45, 96]. On the
other hand we found in our studies that a standardized
preparation of EP retained its ful l antiviral activ ity over
several years, provided that storage conditions were appro-
priate (unpublished results). Similarly, preparations of EP
maintained their cytokine-stimulating activity after storage
for two years [123].
The presence of multiple antiviral ac tivities among
dierent extracts and fractions suggests that many kinds
of Echinacea preparation, such as tinctures, sprays, tablets,
teas, and so forth could be beneficial in the treatment of
infections, although not all preparations are likely to be
eective, and a recent study of 10 commercial preparations
highlighted the variability of antiviral activity between
dierent preparations, althoug h lot-to-lot variation was less
evident [45]. In general ethanol-based extracts had greater
antiviral activities than aqueous extracts; but it was not
possible to identify a specific component responsible for
the activity. Furthermore there was no correlation between
antiviral and anti-inflammatory activities.
Some commercial preparations of Echinacea, including
those with EP, comprise mixtures of EP with other non-
Echinacea herbs, the rationale being that two herbs a re
better than one, and three are even better, etc. In this
respect such mixtures may be considered analogous to the
complex mixtures often advocated in Chinese traditional
medicine (TCM) and Ayurvedic medicines. However, this
basic assumption is not necessarily valid, and in preliminary
studies we examined a number of mixtures of EP with other
standard herbs, for antiviral activities. In the majority of
cases the mixtures were much less eective than the EP by
itself and none were better than EP (unpublished data).
Journal of Biomedicine and Biotechnology 11
However since we do not know the exact mechanisms of the
EP antiviral ac tivity, or the nature of the active compounds,
then we cannot explain these phenomena. But the lesson is
obvious, namely, that some EP preparations by themselves
can be potent antiviral agents and should not be mixed with
17. Relevance of Bioactivities to Normal
Echinacea extracts intended for treatment of colds and flu,
and sore throats are normally marketed for oral consump-
tion. The active ingredients therefore acquire immediate
exposure to the mucosal epithelia. According to our studies
with standardized preparations (as described above), the rec-
ommended applications ensure that physiologically relevant
amounts, that is to say, adequate local antiviral, antibacterial,
and anti-inflammatory concentrations, are achieved under
normal conditions of consumption. Subsequent absorption
and metabolism of the various components, however, are less
relevant to this application, since the sites of infection and
inflammation are at the level of airway epithelial tissues.
Nevertheless, it has been demonstrated that alkylamides
(and possibly a dditional components) can be absorbed
quickly into the blood and remain in the circulation for some
time, at least following E. angustifolia administration [124],
although EP extracts tend to have relatively few alkylamides
[6, 7]. Therefore, depending on the exact chemical compo-
sition of the Echinacea extract, there could be b enefits to the
consumer in addition to the initial interactions with the oral
18. Clinical Trials
Numerous studies have been carried out in humans, with
the objective of preventing or treating common colds, and
these have been critically summarized [3, 5, 124, 125].
Unfortunately some of them used inadequately characterized
Echinacea preparations derived, with various extraction
protocols, from dierent species and plant parts. It is likely
that the chemical composition of the extracts, and conse-
quently their bioactivities, diered substantially. Attempts
to rationalize the interpretation of results by the use of
meta-analyses encountered the same problem, namely, the
resulting variability in test materials. Consequently it is no
surprise that the issue is controversial”, and many popular
scientists and pseudoscientists have jumped to conclusions
about the ecacy or lack of ecacy of Echinacea in
preventing or treating the common cold. In spite of these
reservations there was an overall trend towards beneficial
eects of the Echinacea, but equally importantly the safety of
the preparations was confirmed repeatedly, including trials
in children [125127]. A more comprehensive trial that
also includes influenza virus and other respiratory viruses,
incorporating the use of a well-characterized bioactive
Echinacea extract, is needed to confirm the benefits of oral
Echinacea use.
Until that has been done, we are left with overwhelming
anecdotal experience, in addition to the very encourag ing
results from the cell and tissue culture studies and animal
studies, but no definitive conclusion regarding clinical
ecacy in humans.
19. Mechanisms of Action
The results described have indicated that some Echinacea
extracts evidently contain compounds, or combinations of
compounds, with the ability to interact specifically with viral
and microbial targets [13, 17, 62, 128]. In addition, these
extracts can aect various signaling pathways of epithelial
cells and inhibit the virus/bacterium-induced secretion of
cytokines/chemokines and other inflammatory mediators
that were responsible for the pulmonary symptoms. Since
many signaling pathways can be aected by Echinacea in
dierent cell types, including immune cells [47, 59, 97],
it is conceivable that the overall beneficial eects are due
to a particular combination of compounds acting syner-
gistically. Examples of synergism in herbal medicine have
been described and in some cases validated experimentally
[23, 129, 130], and it is likely that certain Echinacea
preparations also display synergism. However, in spite of our
attempts to correlate bioactivities of Echinacea preparations
with recognized chemical markers, that is, polysaccharides,
caeic acid derivatives, and alkylamides [57], we have not
succeeded in doing so. In contrast, preliminary evidence in
our laboratory has implicated other classes of compounds
(unpublished data).
20. Conclusions
These studies on EP indicate multiple act ions of the
herbal preparation, resulting either from the individual
activities of several compounds or the synergistic eect of
dierent compounds. The resulting benefits are: (1) direct
virucidal activity/activities against several viruses involved
in respiratory infections, at concentrations which are not
cytotoxic; (2) direct bactericidal actions against certain
potentially pathogenic respirator y bacteria; (3) inactivation
of other microbial pathogens relevant to humans and their
domesticated animals; (4) reversal of the proinflammatory
response of epithelial cells and tissues to various viruses and
bacteria; (5) modulation of certain immune cell functions;
(6) reversal of the excessive mucin secretion induced by
rhinovirus. These bioactivities result from changes in gene
expression. Thus a combination of these beneficial activities
could reduce the amount of prevailing viable pathogens,
and their transmission and also lead to amelioration of the
symptoms of the infection.
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