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Pharmacotherapeutics of Echinacea purpurea: Gardening shelf to clinic

Authors:
  • Lipidor AB
J Pharm Educ Res Vol. 2, Issue No. 2, December 2011
45
Pharmacotherapeutics of Echinacea purpurea: Gardening shelf to Clinic
Anil Kumar a*, Puneet Rinwa a, Mahendra Kumar Chhabra b
a Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study,
Panjab University, Chandigarh, India
b Department of Pharmacology, Dr. Harvansh Singh Judge Institute of Dental Sciences and Hospitals, Sector 25,
Panjab University, Chandigarh, India
*Email:kumaruips@yahoo.com
Received: November 28, 2011; Accepted: December 06, 2011
ABSTRACT
Medicinal use of Echinacea species has been extensive and is growing, as a treatment for various infectious and
immune related disorders. Extensive research over the last half century has revealed several important functions
of E. purpurea. The lipophilic constituents of E. purpurea, the alkamide in particular, have positive pharmacological
benefits; responsible for the immunostimulation properties. Antifungal activities have also been attributed to
the lipophilic constituents of E. purpurea seed. Most recently studies have shown that all investigated E. purpurea
species did possess radical scavenging activity. Earlier studies have shown that E. purpurea preparations have an
excellent safety profile, while other findings suggest that certain preparations have a considerable anxiolytic
potential. 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.
Keywords: lipophilic; alkamide; immunostimulation; anxiolytic; randomized trials; upper respiratory infection
INTRODUCTION
Medicines derived from plants (phytomedicines) are
becoming increasingly popular as alternative therapies to
traditional Western medicine 1. Remarkably, most of the
natural products experimentally evaluated so far have been
found to be nontoxic or to have effective doses far below
their toxic doses. The role of natural products in human
healthcare cannot be underestimated. An estimated 80%
of individuals in developing countries depend primarily on
natural products to meet their healthcare needs. Recent
surveys suggest that one in three Americans uses
medicinal natural products daily and that possibly one in
two cancer patients (i.e., up to 50% of patients treated in
cancer centers) uses them as well.
Echinacea purpurea, also known as the purple
coneflower belongs to the daisy (Compositae) family, and
the nine of these North American species have a
widespread distribution over prairies, plains and wooded
areas 2. E. purpurea, an herbal medicine has been used
customarily for the treatment of various infectious and
immune related disorders. Though the active
phytochemicals in this plant vary due to age of plant,
portion of plant, growth conditions, geographical location,
and extraction method 3, the most common constituents
present in E. purpurea includes alkylamides, caffeic acid
derivatives, polysaccharides, and lipoproteins 4.
Polysaccharides are typically present at highest
concentration in aqueous or fresh pressed juice extracts
while alkylamides are more likely to be major constituents
in ethanolic extracts. In recent years, it has become one
of the popular herbal products in North America and
Europe as an immune promoter 5,6 and one of the most
popular herbal supplements 7 used to alleviate colds, sore
throats, coughs, other respiratory infections 8,
immunostimulant 9 and also anxiolytic properties 10.
Echinacea is a perennial herb native to the
Midwestern region of North America. It has tall stems,
bears single pink or purple flowers, and has a central cone
that is usually purple or brown in color. The large cone is
actually a seed head with sharp spines that resemble a
stiff comb.
J Pharm Educ Res Vol. 2, Issue No. 2, December 2011
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E. purpurea was first used by Native Americans in
the Central Plains states to treat a variety of illnesses,
from respiratory and digestive problems 11 to snakebite
and blood poisoning. The scientific properties of E.
purpurea were first studied by German scientists in the
1930s, with the result that it is now one of the leading
phytomedicines used in Germany 12. In the US, it is
estimated that around 10% of the population have used it
at some point to fight a cold 13 and its annual sales of an
estimated US$300 million is second only to St. John’s Wort
12. E. purpurea has been used for centuries and this is
not an argument for efficacy, but it does indicate some
degree of safety. The longevity of its use suggests that it
is not just an ancient fad, but perhaps has a true benefit.
The plant is grown in the central and eastern United States
and is cultivated in Europe for treating the common cold,
coughs, bronchitis, and inflammation of the mouth and
pharynx 8.
Pharmacology:
Anti-colds and flu effects: in vitro studies
‘Common colds and flu’’ affect millions of people
every year and they are responsible for significant
morbidity and the risk of respiratory complications,
particularly in children and in immune compromised people
14,15. In addition the acute episode of cold often
accompanied by a significant bacterial infection, which
may lead to more severe pulmonary and other diseases,
as well as inflammatory activity 16,17. According to a study
by Stanisavljevic et al. 18, the antimicrobial activity of E.
purpurea extracts obtained by different extraction
techniques were tested against the seven microorganisms
by the agar well-diffusion method. Independent of the
extraction technique, the ethanolic E. purpurea extracts
shows activity against almost all of the tested
microorganisms; exception is only mould A. niger. The
control treatment (methanol) had no inhibitory effect on
any of the test microorganisms. Sensitivities of S. aureus,
C. albicans, and S. cerevisiae were higher for both E.
purpurea extracts than the case of tested antibiotic
(Erytromycin and Tylosin tartarat). The diameters of
inhibition zone observed for all microorganisms were
larger for extracts obtained by classical extraction than
those by ultrasound extraction. The differences observed
were statistically significant (with 95% confidence
interval) in the case of E. coli, B. subtilis, C. albicans
and S. cerevisiae. The study suggests that 70% aqueous
ethanolic extracts of E. purpurea is a potential source of
active natural and non-toxic substances, which have
functions as antioxidants, antimicrobials and antibiotics.
The extract obtained by the classical extraction from aerial
parts of E. purpurea contained larger amount of bioactive
compound (total phenols and favonoid).
Different parts of E. purpurea have been used
traditionally in North America for the treatment of various
symptoms of ‘colds and flu’’, as well as the treatment of
candidiasis, respiratory diseases, and wound healing 19,20.
Furthermore, certain E. purpurea preparations can
Figure 1: Echinacea purpurea flower Figure 2: Echinacea purpurea plant
J Pharm Educ Res Vol. 2, Issue No. 2, December 2011
47
reverse the pro-inflammatory effects of some viruses in
cultures of human bronchial cells 21. In view of the wide
spread anti-inflammatory (cytokine inhibiting) properties
of E. purpurea 22, it is possible that E. purpurea extract
preparation could be beneficial in any respiratory bacterial
infection, even in the absence of bacterial killing, and this
benefit could extend to the secondary infections that often
accompany viral ‘‘colds and flu’’.
Anti-inflammatory and antioxidant effects: in vitro
and in vivo studies
Echinacea’s claims as an anti-inflammatory rest on
both theoretical and observed inhibition of inflammatory
mechanisms. Inhibition of hyaluronidase was among the
earliest pharmacological properties attributed to Echinacea
23. Hyaluronidase hydrolyzes hyaluroinic acid and
chondroitin, allowing penetration of the ground substance
by fluids containing pro-inflammatory cytokines. Inhibition
of fibroblast activity and collagen-building has been
reported from a number of laboratories 23. One experiment
reported that both herb and root extracts from E.
purpurea inhibited fibroblast-mediated collagen
contraction 24. According to Bauer, cichoric acid has been
implicated as the most potent of Echinacea derived
substances in terms of anti-hyaluronidase inhibition 25.
Wagner has reported lipoxygenase-inhibiting anti-
inflammatory activity attributable to one of E. purpurea’s
isobutylamides, dodecatetraenoic acid 26 . Reported
inhibition of cyclooxygenase and 5-lipoxygenase by
alkamide-rich Echinacea extracts lends mechanistic
credibility to reported anti-inflammatory effects 27 .
Arachidonic acid metabolism and prostaglandin E2
production were reduced by several E. purpurea products
in Rininger’s laboratory 28. According to study by Canlas
et al., 29 various Echinacea extracts can inhibit the
proliferation of three species of trypanosomatids:
Leishmania donovani, Leishmania major, and
Trypanosoma brucei. Despite these encouraging results,
we are still unaware of any randomized, blinded trials
that have demonstrated clinically useful health-enhancing,
anti-inflammatory or wound-healing properties.
Antifungal effects: in vitro and in vivo studies
The seeds of E. purpurea have never been
investigated, and reports on the achene (small dry
indehiscent fruit, with one seed within the thin wall) are
very limited. The achene of E. pallida has a remarkably
low (about five times lower) content of isobutylamides
compared with those of E. angustifolia and E. purpurea
30. The lipophilic constituents of E. purpurea, the alkamide
in particular, have positive pharmacological benefits;
responsible for the immune stimulatory properties of E.
purpurea extracts 31. Antifungal activity 32 and
cyclooxygenase and 5-lipoxygenase inhibitory activities
33 have also been attributed to the lipophilic constituents
of E. purpurea seed. Since oil is expected to be the richest
source of lipophilic constituents and the seeds of E.
purpurea have not been explored, various investigations
focused on the quality of E. purpurea seed oil. Different
industries are now focusing on various studies on complete
utilization of E. purpurea seed oil for the development of
new antifungal products for cosmetic and therapeutic
industries.
Immunomodulating effects: in vitro and in vivo
studies
As a medicinal supplement, E. purpurea is best
known for its abilities to help individuals prevent or minimize
symptoms associated with immune deficiency. The
molecular mechanisms that E. purpurea employs to exert
its immunomodulatory effects are currently under
investigation 34,35. Studies have shown numerous and
varied immunomodulatory properties of E. purpurea in a
variety of animal models both in vitro and in vivo 19.
Experiments have demonstrated that E. purpurea can
modulate production of specific cytokines from rodent
macrophages 36,37,38 both in vitro and in vivo. Further, it
stimulates proliferation of peripheral blood mononuclear
cells (PBMC); increases number of circulating
lymphocytes and monocytes; and increases percentage
of spleen NK cells 39,40. The cells of the innate immune
system, frequently monocytes and macrophages, are the
primary cellular responders to E. purpurea extracts 6.
The effect of E. purpurea extracts on T-cell function
has not been examined extensively. In response to viral
infection, antigen-specific T-cells proliferate, secrete
cytokines, and destroy virally infected cells via T-cell-
mediated cytotoxicity. E. purpurea extracts have been
used to enhance the clearance of viral infection and it is
possible that the potential benefits of E. purpurea involve
T-cells. Macrophages are also important as a first line of
defense against viral infection. Macrophage and/or
monocyte function may be altered by E. purpurea, and
as these cells become activated, TNF-a secretion typically
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increases. According to many studies, E. purpurea
induced immunomodulation appears to occur through
stimulation of non-specific immune system 37. It has been
shown to stimulate the phagocytic activity of the
macrophages 38. One of the study have also demonstrated
an ethanol-extractable myelostimulatory activity in
Echinacea purpurea aerial parts that, when obtained
from commercial herbal supplements, may be antagonized
by medium-chain fatty acids presumably derived from a
non-plant additive 41. According to Khaksary et al. 42, E.
purpurea is more effective than levamisole in decreasing
phenytoin-induced immunosuppression in mouse fetuses.
The immunostimulating effect of E. purpurea is
believed to be caused by four reactions: activating
phagocytosis, stimulating the fibroblasts, increasing
respiratory activity, and increasing mobility of leucocytes
(WHO, 1999). Pharmacology of herbal medicine is rather
complex as herbal preparations contain a whole array of
chemical compounds working together. Most often there
is only a rather incomplete knowledge of their
bioavailability, and besides, some of the active components
may have remained undetected, or the activity even
ascribed to the wrong constituent(s) 43. All together this
makes it often hard to explain the molecular mechanism
behind any observed effect. In addition some of the active
compounds may create a synergistic effect in the body,
which further complicates the understanding of the
mechanism.
According to a study by Sadigh-Eteghad et al.,44 the
synergetic effects of oral administration of levamisole (2
mg/kg) and Echinacea purpurea (500 mg/kg) was
observed on immune response in Wistar rat after a period
of 4 weeks. Another study by Cundell et al., 37 used E.
purpurea (50 mg/kg of aerial parts; equivalent to
recommended human dosage) mixed with peanut butter
alone was provided to 16 male Sprague–Dawley rats
during an 8-week period. In this study, it was shown for
the first time that oral ingestion of E. purpurea resulted
in a more than a 30-fold increase in circulating IL-2 levels
which demonstrated an immediate and sustained increase
in the percentage of mononuclear cells, thereby
stimulating the immune system.
However, despite the popularity of the herb in its many
forms (capsules, tables, dried root and liquid), and the
fact that over 400 scientific papers have been written
about E. purpurea ability to ‘‘boost the immune system’’
both in vitro and in vivo, its true mode of action remains
poorly understood
Anti-anxiolytic effects: Animal studies
No major psychotropic effects of E. purpurea have
been reported so far, although some recently reported
active constituents are behaviorally active. Based on the
study by Haller et al. 10, anxiolytic potential of five
different E. purpurea preparations was evaluated. Three
of them decreased anxiety but two of them had a very
narrow effective dose range. Only one extract decreased
anxiety within a wide dose-range (3–8 mg/kg). Anxiolytic
effects were consistently seen in three different tests of
anxiety, the elevated plus-maze, social interaction and
shock-induced social avoidance tests. No locomotor
suppressant effects were seen at any dose. Noteworthy,
the doses that showed anxiolytic effects in the study were
much lower than those used in the laboratory models of
the traditional indications. Perceived and real risks of
conventional medications increase the demand for
alternative therapies, provided that these are safe and
efficient. One of the studies also uncovered the potential
effects of an Echinacea preparation on neuronal operations
in the hippocampus, a brain region that is involved in
anxiety and anxiety-related behaviors 45. Earlier evidence
shows that E. purpurea preparations have an excellent
safety profile, while these findings suggest for the first
time that certain preparations have a considerable
anxiolytic potential. Further research is required to identify
factors that differentiate efficient and inefficient
preparations.
Against Influenza infection: in vitro and in vivo
studies
Influenza is a contagious, acute respiratory disease
caused by infection of the host respiratory tract mucosa
by an influenza virus. Influenza accounts for more than
30,000 deaths and a cost of 87 billion US$ annually in the
United States alone. The severity of illness during influenza
infection depends on virus-host interactions. Consumers
frequently use herbal remedies for amelioration of
symptoms of influenza although this approach has not been
validated in clinical trials 46. E. purpurea has become the
most popular commercial herbal preparation in North
America and Europe against this infection 20. Recent in
vitro studies show that E. purpurea combined root and
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aerial ethanol extract inhibits influenza virus entry 47 but
there is limited data related to in vivo effects of E.
purpurea. Mouse models of influenza A virus infection
provide a well established experimental system to study
immune response to influenza infection. Weight loss is a
validated surrogate marker of severity of illness and
predictor of mortality 48,49. To characterize a potential
immunomodulatory effect of E. purpurea there has been
an established mouse model of live H1N1 influenza A
infection. In this model, clinical affects (weight loss) 46
lung viral titers 47 and cytokine levels 50 were consistent
with influenza effects described in the literature. These
findings confirm that the model is a valid platform for
evaluation of E. purpurea effects on influenza infection.
The results indicate that E. purpurea aerial (nonroot)
polysaccharide extract modifies influenza-related clinical
course and immune response, as measured by cytokines,
with decreased pulmonary and systemic KC (human IL-
8) early in influenza infection then decreased pulmonary
and systemic IL-10 and systemic IFN later in the course
of infection. It is interesting to note that, in vitro, root-
containing extract from the same E. purpurea species
and a similar preparation method did have antiviral activity,
reinforcing the likely unique characteristics of distinct plant
parts 4 6. It is possible that some form of the extract
described in the study could be useful for influenza
treatment or prophylaxis against post-viral bacterial
pneumonia, which is possibly mediated by elevated IL-10
following influenza. However, the observed inhibitory
effects could worsen post-influenza pneumonia, so further
studies would be required to evaluate the effect of E.
purpurea in this setting. Further studies are needed to
establish the clinically relevant dose in humans. As clinical
challenges related to influenza continue to escalate, further,
systematic evaluation of this compound may be useful.
Treatment of upper respiratory infection: Clinical
trials
E. purpurea has gained substantial interest and been
the focus of several investigations in clinical trials.
Although a variety of placebo-controlled trials have shown
a lack of benefit for E. purpurea for either prevention or
treatment of upper respiratory tract infections (URIs)
among adults 51,52 the evidence is not completely
unequivocal 53,54. Thus, some interest still exists in
investigating the potential utility of this herbal medicine.
A double-blind, randomized, placebo-controlled trial in
COPD patients with acute URI for Echinacea purpurea
was carried out in 108 male patients (age: 40-81 years)
55. Patients were given ciprofloxacin for 7 days and
additionally one tablet per day of Echinacea purpurea
along with zinc, selenium and ascorbic acid until day 14.
The combination alleviated exacerbation symptoms caused
by URI in COPD patients. Another randomised, double-
blind, placebo-controlled trial of E. purpurea for the
treatment of URIs in children 56 has several strengths. It
was extremely rigorous in its methods and focused on
the duration and severity of URIs as well as the safety of
E. purpurea. The rigor in the methods is a particular
strength, because it removes from this study the
appropriate criticism of weak scientific methods that has
been leveled at earlier assessments of E. purpurea.
Moreover, by focusing on children, this study extends
knowledge on the utility of E. purpurea beyond previous
adult-only studies. E. purpurea was not associated with
either decreased duration or severity of URIs. There was
no overall difference between groups in terms of adverse
events, although rash was more common among children
receiving E. purpurea. Consequently, this well-done study
adds to the accumulating evidence that there is little to no
benefit in using E. purpurea for URIs.
This is due, at least in part, to the diversity of
methodologies and E. purpurea preparations used.
Several human studies have suggested that E. purpurea
stimulates neutrophil and macrophage phagocytic function
40,57 and the production of the cytokines interleukin-1 and
tumor necrosis factor 40,57. The final issue in evaluating
the activity of E. purpurea also comes from the fact
that variations have been demonstrated in both species
(E. purpurea and E. pallida) and plant components
(aerial components or roots) being used, as well as the
extraction methods used to prepare the active ingredients
12. Although the majority of clinical trials of the herb have
to date been performed on either children or young adults
in the 20–30 age group in reality, regular purchasers and
users of the herb are more likely to be older individuals.
Treatment of Induced Rhinovirus Colds: Clinical
trials
Rhinoviruses are the most common agent causing
upper respiratory tract diseases that can also be
associated with asthma exacerbations, otitis media, acute
sinusitis, and even subsequent development of pneumonia
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58,59. The efficacy of Echinacea in a 3-D tissue model of
human airway epithelium was checked and the results
were confirmed by measurements of mucin secretions,
which were stimulated by infection with rhinovirus type
1A but reversed by Echinacea, suggesting that mucus
production during colds could be ameliorated by
Echinacea 60. Experimentally although some clinical
studies of E. purpurea in spontaneously occurring colds
have reported positive results, others have reported
negative findings, so that the efficacy of E. purpurea
remains uncertain 19,20. Moreover, the quality of many
clinical trials, and of some investigated products, has been
challenged 6 1. Variation among the extracts used,
medication regimens, and study designs might be partly
responsible for the conflicting outcomes 62. A recent
Cochrane review 63 found five randomized trials of
adequate methodologic quality that investigated the
prophylactic efficacy of E. purpurea in spontaneously
acquired colds. In two studies, a statistically significant
reduction in the incidence of upper respiratory tract
infections was observed 64. One trial found a significantly
shorter duration of cold episodes in the E. purpurea
treated group 65. The authors concluded that there was
still insufficient evidence to promote E. purpurea for the
prevention of common colds and commented that the
observed effect size (ie, the difference in mean values
between groups) of 5% to 15% was of questionable
clinical relevance. However, several other studies of the
efficacy of E. purpurea for the treatment of the common
cold have produced positive results. For example, in a
study investigating an alcoholic fresh-plant tincture from
E purpurea, treatment was associated with 120% better
resolution of symptoms during a cold episode than was
placebo (P=0.02). This double-blind, placebo controlled,
randomized clinical trial investigated the relative reduction
of 12 cold-related symptoms, rated on a scale ranging
from 0 (absent) to 3 (severe) in 246 patients. Detailed
and comprehensive reviews on the efficacy of E.
purpurea in the prevention and treatment of the
spontaneous common cold were recently published by
Barrett, 2003 19 and Barnes et al., 2005 20. In various
trials with E. purpurea, the start of medication varied
from the time of occurrence of first symptoms to several
hours afterward; therefore, it is not surprising that the
outcome of these studies differed substantially.
Unfortunately, such variables within a normal field study
of the common cold are difficult to circumvent; thus, this
system can result in a critical divergence of results 66,67.
Three rhinovirus inoculation studies investigated the
prophylactic effects of well-standardized E. purpurea
extracts 68. In these studies, the rate of infection (defined
by detection of rhinoviruses in nasal secretions and/or
rise of antibody titers in the serum) was investigated as a
primary outcome variable. All trials reported a negative
outcome in the prevention of infection. In all three studies,
E. purpurea appeared to inhibit development and severity
of symptomatic colds, although no significant difference
from placebo was found. Measures of variance in the
data were generally high. With an expected effect size of
10% to 40%, it is possible that these studies were
underpowered to detect any benefit for the parameters
likely to be influenced by E. purpurea 19,20. The statistical
power was calculated to be 29% for the study published
by Sperber et al., 68 and 15% for those from Turner et al.
53 .
Perhaps due to the lack of specific therapies,
associated risks with certain treatment, and the relatively
mild nature of the symptoms, phytomedicines are a popular
approach to managing the common cold. In recent years,
different clinical trials across various cities of US have
proved that E. purpurea extracts have decreased the
duration, the severity, and the frequency of symptoms of
the common cold 69. Despite for being a major potential
source of highly valued pharmaceutical compounds, as
well as has received a global attention because of
Echinacea is listed as the first among 11 top-selling herbal
extracts in North America 70.
Precautions
The use of herbs is a time honored approach in
strengthening the body and treating disease. However,
herbs contain active substances that may trigger side
effects and interact with other herbs, supplements, or
medications. For these reasons, people should take herbs
under the supervision of a practitioner knowledgeable in
the field of botanical medicine. People with tuberculosis,
leukemia, diabetes, connective tissue disorders, multiple
sclerosis, HIV or AIDS, any autoimmune diseases, or,
possibly, liver disorders should not take E. purpurea.
There is some concern that E. purpurea may reduce the
effectiveness of medications that suppress the immune
system. For this reason, people receiving organ transplants
J Pharm Educ Res Vol. 2, Issue No. 2, December 2011
51
who must take immunosuppressant medications should
avoid this herb. In rare cases, E. purpurea may cause
allergic reactions ranging from a mild rash to anaphylaxis
(a life threatening reaction accompanied by throat
tightening, shortness of breath, and, possibly, fainting).
People with asthma and allergies may be at an increased
risk for developing these adverse reactions. People with
allergies to plants in the daisy family (compositae) should
not take this herb unless they do so under the supervision
of a health care provider. There has been one report of
an individual developing erythema nodosum (a painful skin
condition) after taking E. purpurea to treat the flu. When
taken by mouth, E. purpurea may cause temporary
numbing and tingling on the tongue. Despite concerns that
this drug may be unsafe for pregnant or breastfeeding
women, evidence suggests that the use of E. purpurea
during pregnancy does not increase the risk of birth defects
or other pregnancy related health problems.
Possible Interactions
E. purpurea should be used with a caution or must
be constulted with practitioner 71, 72. For example, when
E. purpurea is co-administered with econazole, an
antifungal agent, the remission chances of fungal
infections are significantly reduced. Besides, E. purpurea
should not be taken along with immunosuppressive
medications (in case of organ transplant) as it stimulates
the immune system. E. purpurea is beneficial when used
in combination with cyclophosphamide in cancer
treatment. The combination causes dual function of
fighting against cancer as well as enhances immune
system.
Conclusion and perspectives
Extensive research over the last half century has
made clear that most chronic illnesses can only be cured
by multi-targeted as opposed to mono-targeted, therapy
and that promiscuous targeting of a disease cell’s multiple
bypass mechanisms is a therapeutic virtue. Consequently,
agents that can modulate multiple cellular targets are now
attractive objects of research. As this review has shown,
it is one such agent and has the potential to treat a variety
of diseases. More extensive, well-controlled clinical trials
are now needed to fully evaluate its potential in terms of
optimal dose, route of administration, and disease targets
and potential interactions with other drugs. In light of the
long and established experience with E. purpurea as a
foodstuff and as a natural medicine in humans, its low
cost, its proven chemo preventive and therapeutic
potential, and its pharmacological safety, E. purpurea is
moving rapidly from the gardening shelf toward the clinic.
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Article
Echinacea species is provided as dietary supplements for various infectious and immune related disorders and has a potential role in cancer prevention. The aim of this study was to optimize the extraction of total flavonoids using different extraction methods and investigate the cytotoxic effects on various cancer cell lines (CaCo-2, MCF-7, A549, U87MG, and HeLa) and VERO (African green monkey) as a non-cancerous cell line. Box-Behnken statistical design was used to evaluate the effect of pressure (100-200 bar), temperature (40-80 degrees C) and ethanol as co-solvent (6-20 wt%) at a flow rate of 15 g/min for 60 min in supercritical CO2 extraction and the effect of temperature (60-100 degrees C), time (5-15 min) and power (300-900W) in microwave-assisted extraction. Optimum extraction conditions were elicited as 300 bar, 80 degrees C and 13% co-solvent yielding 0.472 mg rutin equivalent total flavonoids/g extract in SC-CO2 extraction, whereas 60 degrees C, 10 min and 300W yielded the highest (0.202 mg rutin equivalent) total flavonoids in microwave-assisted extraction. Additional trials with subcritical water (0.022 mg/g) and Soxhlet extraction with methanol (0.238 mg/g) yielded lower flavonoid contents. The exposures upto 50 mu g/ml of extracts revealed no significant inhibition on the proliferation of both tested cancer cells and healthy VERO cells.
Article
The US Phytotherapeutical Market still increases considerably. The article presents the different reasons which are responsible for this expansion and lists the most important herbal medicines of the USA including the categories of use. The US regulatory categories for herbal products are presented as well as the current efforts which are undertaken in order to guarantee product quality and to establish the effectiveness of herbal products.
Article
Antioxidant and antimicrobial activities of Echinacea purpurea L. (Asteraceae) extracts obtained by classical and ultrasound solvent extraction were compared. The dry aerial part of plant was extracted by 70% ethanol at a solid-to-liquid ratio of 1?10 (m/v) and 25°C. The extract obtained by classical solvent extraction contained 29% larger amounts of phenolic compounds and 20% higher content of flavonoids. 2,2-diphenyl-1-picril hydrazyl radical (DPPH) scavenging reached 93.6% and the values of EC50 were (34.16±0.65) ?g·ml ?1 and (65.48±1.12) ?g·ml ?1 for the extracts obtained by the classical and ultrasound extractions, respectively. The extracts, independent of the extraction technique applied, showed a considerable growth inhibition on Candida albicans and Saccharomyces cerevisiae, while no growth inhibition zones were observed for Aspergillus niger. The diameters of inhibition zone observed for all the microorganisms were larger for extracts obtained by classical extraction than those by ultrasound extraction.
Article
Echinacea phytopharmaceuticals represent the most popular group of herbal immunostimulants in Europe and in the USA [1, 2]. According to a recent report, Echinacea products have been the best selling herbal products in natural food stores in the USA in 1997 with 11.93% (1996: 9.6%) of herbal supplement sales [3]. Including homeopathic preparations, more than 800 Echinacea-containing drugs are currently on the market in Germany. Most of the preparations contain the expressed sap of Echinacea purpurea aerial parts, or hydroalcoholic tinctures of E. pallida or E. purpurea roots. They are mainly used for the treatment of colds and infections [4]. Clinical effects have been demonstrated for the expressed sap of the aerial parts of Echinacea purpurea in the adjuvant therapy of relapsing infections of the respiratory and urinary tracts, as well as for alcoholic tinctures of E. pallida and E. purpurea roots as adjuvants in the therapy of the common cold and flu [5, 6]. In the USA, it is mostly encapsulated powders from roots and aerial parts, but also tinctures from the roots and aerial parts that are used. Many investigations of the constituents of Echinacea have been undertaken. So far, compounds from the classes of caffeic acid derivatives, flavonoids, polyacetylenes, alkamides, pyrrolizidine alkaloids, polysaccharides and glycoproteins have been isolated [7]. For the main interest of finding the active component, but also for standardization purposes, the question on the chemical composition of Echinacea herbs and preparations is essential. Therefore, the present knowledge on the chemical constituents, analysis, and immunomodulatory effects of Echinacea preparations shall be reviewed.
Article
Question. How safe and effective is Echinacea purpurea at reducing the duration and severity of upper respiratory tract infections in children? Study design. Multicentre randomised controlled trial. Main results. There was no significant difference in duration or severity of symptoms with Echinacea purpurea compared with placebo in children with upper respiratory tract infection (median duration of symptoms (95% CI): 9 days (8 to 10 days) with Echinacea vs. 9 days (8 to 10 days) with placebo; P=0.89; median severity of symptoms (95% CI): 33 (29 to 40) with Echinacea vs. 33 (30 to 38) with placebo; P=0.69). Rash occurred in significantly more children receiving Echinacea compared with placebo (reports of rash: 24 with Echinacea v 10 with placebo; P=0.008). Authors' conclusions. Echinacea purpurea is ineffective for treating upper respiratory tract infections in children aged 2 to 11 years.
Article
The increasing global demand for biomass of medicinal plant resources reflects the issues and crisis created by diminishing renewable resources and increasing consumer populations. Moreover, diverse usage of plants and reduced land for cultivation in the world accelerated the deficiency of plant resources. In addition, the preparation of safety of plant based medicine whips up demand for biomass of valuable medicinal plants. As one of alternative approach to upswing the productivity of plant-based pharmaceutical compounds, automation of adventitious root culture system in airlift bioreactor was adopted to produce cosmic amount of root biomass along with enriched diverse bioactive molecules. In this review, various physiological, engineering parameters, and selection of proper cultivation strategy (fed-batch, two-stage etc.) affecting the biomass production and secondary metabolite accumulation have been discussed. In addition, advances in adventi-tious root cultures including factors for process scale-up as well as recent research aimed at maximizing automation of the bioreactor production processes are also highlighted. Examples of the scale-up of cultures of adventitious roots of Morinda citrifolia, Echinacea purpurea and angustifolia, Hypericum perforatum and Panax ginseng by applying 20 L to 10,000 L bioreactors in our lab were demonstrated with a view of commercial application.
Article
We performed a systematic review of controlled clinical trials to check the evidence for the immunomodulatory efficacy of preparations containing extracts of Echinacea. Trials were searched by on-line searches in Medline and Embase, a search in the private database Phytodok, contacts with researchers and drug companies, and by checking references in available articles. All available historically and prospectively controlled trials investigating the prophylactic or therapeutic immunomodulatory activity of preparations of Echinacea alone or in combination with other plant extracts or homeopathic dilutions in humans were included. Study characteristics, results, and conclusions of primary authors were analyzed using standardized evaluation forms and methodological quality assessment using a predefined score system. A total of 26 controlled clinical trials (18 randomized, 11 double-blind) were identified; 6 of these involved testing three different mono-extracts, and 20 involved testing three different preparations also containing other ingredients. Nineteen trials studied the efficacy of the prophylactic or curative treatment of infections; 4 trials the reduction of side-effects of antineoplastic therapies and 3 trials the modulation of various laboratory immune parameters. The primary authors claimed that 30 of the 34 treatment strategies showed a superior efficacy to those of the control groups. The methodological quality of most studies was low and only 8 trials scored more than half of the maximum possible score points. Existing controlled clinical trials indicate that preparations containing extracts of Echinacea can be efficacious immunomodulators. However, the evidence is still insufficient for clear therapeutic recommendations as to which preparation to use and which dose to employ for a specific indication. Further methodologically sound, randomized clinical trials should be conducted.
Article
Echinacea (pronounced eck-in-ay'-shuh) is among the best-selling herbal remedies in the United States, accounting for 8% of total sales of botanical supplements. Many people hope that by taking echinacea they will reduce their chances of developing the common cold or the flu, or at least shorten the severity and duration of these viral maladies. Annual retail sales of echinacea in this country are variously estimated at $125-$300 million. A recent national survey of Canadians found that 32% had taken it to fight a cold.