®

Polinacea
A patented* Echinacea
angustifolia
root extract
........................
Triple standardization
in different components
........................
Unique pharmacological
and human data are
available
........................ Echinacea angustifolia
Supported by two
preliminary clinical studies

The traditional medicinal use of Echinacea angustifolia
can be traced back to the ethnopharmacology of Native
Americans who employed the plants for many purposes that
relate to the addressing the natural inflammatory response
function.[1-3] Echinacea was also a popular natural remedy in
the United States, and was included in the National Formulary
of the United States from 1916 to 1950. Notwithstanding the
growing use of synthetic drugs, the use of Echinacea was
rekindled by European studies in the second half of the past
century, and Echinacea has become one of the most popular
dietary supplements.
According to the National Institute of Allergy and Infectious
Diseases, the US population experiences 1 billion respiratory
challenges every year, and Echinacea, known for its
immunostimulatory effects, is the most common nutraceutical
consumed in the US to address these challenges.[4]
A number of mixed clinical data are available in literature on
products obtained from different species of Echinacea, using
different plant parts and solvents. The indications for these
products are generally to support and maintain a healthy
immune system.
The available clinical information has been recently reviewed
by Barret,[5] who concluded that the globality of the data
supports the use of Echinacea in the treatment of respiratory
challenges, reflecting the most widespread utilization.
However, research on efficacy has produced also mixed
results.[6]
These mixed findings are not surprising, since the term
“Echinacea-based preparations” encompasses extracts
obtained using varying extraction methods and solvents, from
different Echinacea species, and from different parts of these
plants (e.g., aerial versus underground parts), with marked
differences in terms of constituent profiles.
Polinacea®, extracted exclusively from the roots of E.
angustifolia, is a immonomodulating standardized extract,
studied and patented by Indena.

Please note this documentation is available for various countries all over the world
and hence it may contain statements or product classification not applicable to
your country. The claims made are in reference to ingredients only, hence they
do not refer to finished products and they may not comply with Regulation EC
n. 1924/2006. The marketer of any finished product containing any ingredient
is responsible for assuring that the destination of the product and the claims
made for the finished product are lawful and comply with all applicable laws
and regulations of the country or countries in which the product is to be sold.

* Patent No.: US 6,881,426

Clinical use[7]

Two recent preliminary clinical studies conducted at a
time of seasonal change, have evaluated the efficacy of
Polinacea® to support respiratory health.
The first pilot study enrolled 38 adults. The volunteers
were sorted out into three groups, receiving a conventional
allopathic intervention, group Polinacea®, or a combination
of conventional allopathic intervention Polinacea®,
respectively. Polinacea® was administered orally at the
dosage of 200 mg/day for the first 15 days of the study,
and the dosage was next reduced to 100 mg/die for the
following 15 days and to 100 mg/die on alternative days for
the remaining 60 days.
The administration of Polinacea® showed improvements
on the overall subject conditions, and the volunteers who
received the combination of Polinacea® and conventional
allopathic intervention experienced the least respiratory
challenge during the time frame of the study.

Challenge-like Semi-challenge-like
Group (n) Challenge Mild
Symptoms Symptoms

Conventional allopathic
0 5 3
intervention Group (14)

Polinacea® Group (12) 1 1 1

Conventional allopathic
intervention + Polinacea® 0 1 0
Group (12)
Effect of oral administration of Polinacea® on adult subjects with existing respiratory challenges.

The second pilot study enrolled 34 healthy pediatric
subjects (whose participation was authorized by their
parents and overseen by an Ethical Committee in
accordance with Good Clinical Practice guidelines), who
received Polinacea® (100 mg/die for the first 30 days, then
reduced to 100 mg/die every other day for the following 60
days) or a B vitamin supplement. None of the participants
received conventional allopathic intervention, and at the
end of the three-month study, a reduction in the occurency
of respiratory tract challenges was observed in the
Polinacea® branch.

Challenge-like Semi-challenge-like
Group (n) Challenge Mild
Symptoms Symptoms

Polinacea® Group (14) 1 1 0

Vitamin Complex (20) 2 6 0

Effect of oral administration of Polinacea® on healthy subjects.

A new pilot study[8] involving 10 human healthy volunteers
has provided a putative mechanistic basis.
After four weeks of administration of 100 mg Polinacea®
as a syrup, genomic analysis (mRNA levels in lympho- and
monocytes) evidenced a upregulation of the production of
the cytokines IL-2 and IL-8, associated to downregulation
of the production of IL-6 and TNF-a cytokines.
Plasma measurements confirmed these changes, except
for TNF-a, whose levels were not significantly changed.
These results further support the concept that Polinacea®
can modulate cytokine expression in humans, positively
supporting respiratory health.
Pharmacology[9]

Polinacea® potential as an immune response enhancer is
based on the results obtained in several in vitro models.
In order to avoid an unspecific response of the immune
competent cells for the in vitro studies, samples of
Polinacea® were purified from lipopolysaccharides (LPS)
of bacterial origin, which are a possible contaminant of
the plant root utilized for the extraction. LPS, in fact, are
reported to produce a non specific immune response on
macrophages in vitro.
In immunocompetent mice challenged with Leishmania
major (one of the most representative experimental animal
models utilized to ascertain the immunoboosting capability
of substances), Polinacea® reduced by over 25% the
experimentally induced leishmaniasis (mortality at week 1).
Moreover, Polinacea® orally administered at the dose of 1g/
kg day for 7 days was effective (30%) in counteracting the
mortality induced by Candida albicans in immunocompetent
mice; even in the case of Cyclosporin-immunosuppressed
mice, Polinacea® was able to prevent animal death by 40%.

Treatment n Survivors

Candida albicans 10 0

Candida albicans + Polinacea® (1g/kg day x 7 days) 20 6*

Candida albicans + Cyclosporin A (1g/kg day x 7 days) 10 0

Candida albicans + Cyclosporin A + Polinacea® (1g/kg day x 7 days) 10 4*

Effect of oral administration of Polinacea® on survival in normal and immunosuppressed mice infected with Candida albicans.
*p< 0.01 vs control

Polinacea® intraperitoneally administered at the dose of of 2 μg/kg day, corresponding to the amount administered
0.1g/kg day was effective in counteracting mortality induced in LPS-containing Polinacea®, was practically ineffective.
by Candida albicans. This effect was also supported by the
fact that LPS (lipopolysaccharides), administered at a dose

In terms of mechanism of action, there are animal models

800
to confirm the hypothesis of a direct action on T cells:
*p<0.01 vs anti-CD3 *
Polinacea® and IDN 5405 have been both deprived of 700

LPS (responsible of non specific immune response). 600

They have been shown to dose dependently stimulate 500 0.1 µg/ml
* *
anti-CD3-treated isolated T limphocytes to produce and *
pg/ml IFN-g

1.0 µg/ml

release interferon-g (IFN-g). Anti-CD3 are reported to 400 10 µg/ml

*
affect immune responses by inducing immune regulation.[9] 300

These results have been paralleled by a good response 200

in terms of cell proliferation of T lymphocytes. In the same

100
animal model, a reference product (selling well-established
European Echinacea), compared to a placebo, has not 0
control anti-CD3 anti-CD3+Polinacea® anti-CD3+IDN 5405
given statistically significant results.

Effect of Polinacea® and IDN5405 on IFN-g

production by anti-CD3-treated human T lymphocytes.
 Suggested dosage: 100-200 mg/day

Chemical profile

Polinacea® is a standardized extract from the roots of a

wild E. angustifolia variety, selected and cultivated by
Indena. The extract is standardized in echinacoside
(≥2%), and a structurally unique high molecular weight
polysaccharide characterized by a the presence of a partially
carboxymethylated and partially acetylated polygalacturonic
acids, with accompanying rhamnogalacturonan (≥5%),
named IDN 5405. High molecular weight
The occurrence of this polysaccharide in the roots of E. polysaccharide from
angustifolia was first reported by an Indena research group. Polinacea®.
IDN 5405 is a polysaccharide that has been highlighted for
the first time in the root of E. angustifolia.

Standardized compound Chemical nature Content (%)

Echinacoside Caffeic acid derivative ≥ 2%
IDN 5405 High molecular weight polysaccharide ≥ 5%
Isobutylamides Amides ≤ 0.1%
Triple standardization of Polinacea®.

Echinacea angustifolia root extract

with a unique triple standardization

Polinacea® has a unique triple standardization in the following

Echinacoside HPLC chromatogram.
constituents: echinacoside, a caffeoylated polyphenol of the 0.30

phenylethanoid class; IDN 5405, a high molecular weight 0.28

- 12.700

polysaccharide of ca. 20,000 Da. identified for the very first

ECHINACOSIDE

0.26

time in the E. angustifolia; Polinacea® is also standardized

Echinacoside

0.24

for being devoid of alkamides (isobutylamides) (≤0.1%). 0.22

Isobutylamides have a powerful inflammatory response 0.20

support function, mediated by the activation of the peripheral

0.18

cannabinoid receptor.[11] Consequently, consumption of

0.16
isobutylamiderich Echinacea preparations may contribute
AU

to supporting a healthy inflammatory response during an 0.14

challenge in progress, but might not exert any immuno- 0.12

stimulating or overall effect on morbidity.[11] When this 0.10

information is combined with their chemical instability[11] and 0.08

the current limited knowledge of their toxicity, it provides a 0.06

rationale for removing alkamides from Echinacea extracts 0.04

intended to be used exclusively for immuno-stimulating 0.02

purposes. Thus, while Polinacea® is more indicated 0.00

for the prevention of respiratory challenges, Echinacea 0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 45.00 50.00
Minutes
preparations rich in isobutylamides might be more useful to
alleviate the symptoms of this condition.
Safety profile
The studies conducted on Polinacea® (oral acute and
subacute toxicity) indicate that the product has no
toxic effect at all tested dosages. No signs of any clear
toxicological effect were seen in the subacute toxicity at any
of the dose levels investigated (100, 300 and 1000 mg/kg/
Botanical profile
Echinacea angustifolia DC (narrow leaved-purple
coneflower) is one of the “coneflowers”, a group of Native
American wildflowers from Asteraceae family characterized
by spiny flowering heads and with an elevated receptacle
which forms the “cone”. The species is a herbaceous
perennial, and flowers late in Spring-mid Summer, forming
vertical taproots in dry prairies, barrens, rocky sandy soil
from Texas to Saskatchewan, ands from Western Iowa
to Minnesota.[13,14] The ethnopharmacology of Native
Americans underlies most of our knowledge on North
American plants. and Echinacea spp. represent the most
relevant example.[14]
Samples of Echinacea spp. have been found in
archeological digs of Lakota Sioux village sites from 1600s
and most of the information we have on the ethnobotany of
Conclusive remarks
The in vivo studies conducted on Polinacea® revealed its
immune boosting capacity despite the presence of LPS
activating macrophages.
The positive results on the in vitro T cells suggest Polinacea®
is effective when employed as immunostimulant. Its
action is seemingly related to the combined action of an
immunostimulating polysaccharide (IDN 5405) and the
properties of the polyphenolic echinacoside.
day) and thus, the dose of 1g/kg/day may be considered
the “no observed adverse effect level” – NOAEL, based on
these studies.
Echinacea spp. comes from Native American tribes.
For traditional medicinal purpose and ornamental purposes,
three different species are cultivated: Echinacea angustifolia
DC, E. pallida (Nutt.) Nutt. and E. purpurea (L.) Moench. The
first two species are often confused; in particular the more
abundant and easily cultivated E. pallida is traded under the
name of E. angustifolia, a species better documented in
terms of biological activity.[16]
Indena’s Quality Control by morphological and chemical
examination can distinguish these two species. Furthermore,
in order to improve the consistency and quality
of its product, Indena has established dedicated plantations
to provide its supply of E. angustifolia.
A few milestones about Polinacea®:
- selected cultivated Echinacea angustifolia plants
- innovative extraction procedure
- unique triple standardization
- low level of isobutylamides
- direct immunological effect on T cells
- well tolerated in acute and subacute toxicity
- shown effective in conjunction with conventional allopathic
intervention in two pilot clinical studies.
References
1. Hobbs C, “The Echinacea Handbook“, Sandy, OR;
Eclectic Medical Publications; 1989.
2. Flannery MA, “From Rudbeckia to Echinacea:
the emerge of the purple coneflower in modern
therapeutics”, Pharm. Hist. 1999, 41-52.
3. Foster S, “Echinacea: Nature’s Immune Enhancer”.
Rochester, VT: Healing Arts Press; 1991.
4. Shah SA et al,”Evaluation of echinacea for the
prevention of common cold”, The Lancet 2007, 7,
473-480.
5. Barret B,” Medicinal properties of Echinacea:
a critical review.” Phytomedicine 2003, 10 (1),
66-86.
6. Woelkart K., Linde K., Bauer R., “Echinacea for
preventing and treating the common cold”, Planta
Med 2008; 74: 633-637
7. Di Pierro F, Rapacioli G, Ferrara T, Togni S, “Use of
a Standardized Extract from Echinacea angustifolia
(Polinacea®) for the Prevention of Respiratory Tract
Infections”, Alt. Med. Rev. 12, 2012, 36-41
Indena S.p.A. - Viale Ortles, 12 - 20139 Milano - Italy
Tel. +39.02.57496.1 - Fax +39.02.57404620
8. Dapasa, B., et al., Immunomodulation medi-
ated by a herbal syrup containing a standardized
Echinacea root extract: A pilot study in healthy
human subjects on cytokine gene expression,
Phytomedicine, 2014 May 27
9. Morazzoni P, Cristoni A, Di Pierro F, Avanzini C, Ra-
varino D, Stornello S, Zucca M, Musso T, “In vitro
and in vivo immune stimulating effects of a new
standardized Echinacea angustifolia root extract
(PolinaceaTM)”, Fitoterapia 76, 2005, 401-411.
10. Herold KC, Taylor L, “Treatment of type 1 diabetes 15. Hobbs C., “ Echinacea: a literature review; botany,
with anti-CD3 monoclonal antibody: induction of history, chemistry, pharmacology, toxicology and
immune regulation?” Immunol. Res., 2003, 28
(2);141-150.
11. Raduer S, et al.,”Alkylamides from Echinacea are a
new class of cannabinomimetics”, J. Biol. Chem.
281, n. 20, 2006, 14192-14206.
12. Vohra S, Adams D, Hudson JB, et al. Selection of
natural health products for clinical trials: a preclincal
template. Can J Physiol Pharmacol 2009:87:371-
378.
13. Oxford University Press, Flora of North America,
vol.21, 2006.
14. Mc Gregor R. L.” The taxonomy of the genus
Echinacea (Compositae)”, Univ. of Kansas Sci.
Bul., 48-132, 1968.
clinical uses”, Special Supplement to Herbalgram
n. 30, 33-48.
16. Bauer R., Kahn I. A., Wagner H.,”TLC and HPLC
analysis of Echinacea pallida and Echinacea
angustifolia roots” Planta Med. 54, 1988, 426-430.
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