Content uploaded by Dugald Seely
Author content
All content in this area was uploaded by Dugald Seely
Content may be subject to copyright.
Abstract. Background: Essiac
®
is a herbal compound that
has been in common use with cancer patients in North
America for over 80 years. Despite its relatively widespread use,
there are no peer-reviewed published reports of in vivo studies
regarding the use of this compound. Materials and Methods:
Essiac
®
was administered orally to test animals prior to all
experiments. Standard assays to test protection from ethanol-
induced gastric ulceration and carbon tetrachloride-induced
hepatic injury were performed on Wistar rats. Assays of post-
glucose-load serum glucose and cellular and humoral immune
modulation were conducted on ICR and BALB/C mice,
respectively. Results: Essiac
®
demonstrated a modest gastric
protective effect via reduction of ethanol-induced gastric
ulceration. However, Essiac
®
did not demonstrate significant
hepatoprotective, hypoglycemic or immunomodulatory
properties. Conclusion: Essiac
®
, administered in established in
vivo experimental models, did not significantly demonstrate its
purported physiological modifying effects.
Complementary and alternative medicine (CAM) use by
oncology patients is widespread, with estimates of 60-85%
reporting at least one use of CAM therapy (1-3). Essiac
®
Tea, a proprietary blend of four herbs, is a popular choice
among breast cancer patients. Surveys estimate usage rates
of between 15%-35% in this population in some sections of
North America (2, 4). Though commonly associated with
breast cancer patients, Essiac
®
is not restricted to this
population, with its use having been reported in patients
suffering from a variety of cancers (5).
Essiac
®
is a blend of the four herbs Arctium Lappa, Rheum
palmatum, Rumex acetosella and Ulmus rubra (6). This
herbal compound has reportedly been used in the treatment
of cancer for over 80 years. Essiac
®
and Essiac
®
-like
products such as Essiac
®
Liquid Extract (a pre-packaged
liquid form of the herbal compound) are purported to
display a variety of therapeutic effects including
immunomodulatory, antineoplastic, hepatoprotective,
gastroprotective and anti-inflammatory properties (6).
Despite a strong recommendation from the Task Force on
Alternative Therapies of the Canadian Breast Cancer
Research Initiative regarding the need for publication of
research into the use of Essiac
®
(7), no research has been
published in the peer-reviewed literature regarding its in an
in vivo model. There are some brief descriptions available
from a series of in vivo experiments conducted at the
National Cancer Institute and Memorial Sloan Kettering
Cancer Center, U.S.A., but these results have not been
submitted for peer-reviewed publication (8).
A recent in vivo study was published involving a similar
herbal compound, Flor-Essence
®
, which contains the four
herbal constituents of Essiac
®
. This study indicated the
potential promotion of mammary tumors after Flor-
Essence
®
exposure in a Sprague-Dawley rat model (9). It
should be noted that Flor-Essence
®
also contains four
additional herbal components not present in Essiac
®
(Nasturtium officinale, Cnicus benedictus, Trifolium pratense
and Laminaria digitata), making it difficult to extrapolate
the results to the context of Essiac
®
administration.
However, these results emphasize the importance of
further research into the effects of Essiac
®
administration
in pre-clinical models.
There is a considerable amount of pre-clinical research
available on the properties of each of the four herbs present
in Essiac
®
(6). Using standard assays developed in rodent
models, some of the purported medicinal properties of
Essiac
®
, administered orally in an in vivo setting, were
investigated to provide preliminary data of these effects.
3057
Correspondence to: Edward Mills, Director of Research, The
Canadian College of Naturopathic Medicine, 1255 Sheppard Ave.
E., Toronto, Ontario, Canada M2K 1E2. Tel: (416) 498-1255, ext.
324, Fax: (416) 498 1643
Key Words: Essiac
®
, in vivo, immune modulation, herbal
compound, complementary and alternative medicine.
ANTICANCER RESEARCH 26: 3057-3064 (2006)
An In Vivo Analysis of the Herbal Compound Essiac
®
BLAIR J.N. LEONARD
1
, DEBORAH A. KENNEDY
2
, FONG-CHI CHENG
3
,
KENG-KUANG CHANG
3
, DUGALD SEELY
2,4
and EDWARD MILLS
2,5
1
Faculty of Medicine, University of Toronto, Toronto, ON;
2
Division of Clinical Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, ON, Canada;
3
MDS Pharma Services-Taiwan Ltd., Peitou, Taipei, Taiwan 112, R.O.C.;
4
Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON;
5
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada
0250-7005/2006 $2.00+.40
Materials and Methods
Animals. One strain of rats and two different strains of mice were used
in the studies, i.e., male Wistar rats and male ICR-derived mice
provided by the animal breeding center of MDS Pharma Services -
Taiwan Ltd., ROC, as well as BALB/c-derived male mice, provided
by the National Laboratory Animals Breeding and Research Center
(NLABRC, ROC). The Wistar rats and ICR mice were housed in
APEC cages while the BALB/c mice were housed in individually
ventilated cages racks (IVC Racks, 36 Mini Isolator systems) under
specific pathogen-free (SPF) conditions. Six rats were allocated
45x23x21 cm living space and the ten mice 29x18x13 cm. All the
animals were maintained in a hygienic environment under controlled
temperature (22Æ-24ÆC) and humidity (60%-80%) with 12-hour
light/dark cycles for at least 1 week in MDS Pharma Services - Taiwan
laboratory prior to use. The rodents had free access to standard
laboratory chow (LabDiet Rodent Diet, PMI Nutrition International,
St. Louis, MO, USA) and tap water. All aspects of this work, including
housing, experimentation and disposal of the animals, were performed
in accordance with the Guide for the Care and Use of Laboratory
Animals, National Academy Press, Washington, DC, 1996.
Reagents. Essiac
®
Liquid Extract, supplied as sold in unopened
bottles direct from the company (Essiac Canada International,
Ottawa, ON, Canada), 5-Fluorouracil (Sigma), acetone (Wako
Pure Chemical Industries, Ltd., Osaka, Japan), ALT (alanine
aminotransferase) assay kit (Wako), AST (aspartate amino-
transferase) assay kit (Wako), carbenoxolone-disodium (Sigma),
carbon tetrachloride, CCl
4
(Wako), D (+) glucose (Merck KGaA,
Darmstadt, Germany), ethanol (Merck), Glucose-HA assay kit
(Wako), glibenclamide (Sigma), Hemolynac.3 Hemolys (Nihon
Kohden, Tokyo, Japan), isotonac.3 diluent (Nihon Kohden),
lipopolysaccharide (Sigma), olive oil (Wako), oxazolone (Sigma),
phosphated-buffered saline, PBS, pH 7.4 (Sigma), rabbit red blood
cells (Home-Made), Silymarin (Aldrich, St. Louis, MO, USA),
sodium chloride (Wako) and Tween 80 (Wako).
Equipment. Twelve channel pipetman (Costar, Acton, MA, USA),
96-well polystyrene plate (Costar), animal case (ShinTech, Taipei,
Taiwan, ROC), automatic analyzer 7050 model (Hitachi, Tokyo,
Japan), centrifuge 5417R (Eppendorf, Eppendorf, Germany),
disposable syringe (1 ml, Top Corporation, Tokyo, Japan), Dyer
Model micrometer gauge (Peacock, Tokyo, Japan), EDTA K tube
(Sarstedt, Nürmbrecht, Germany), electronic scale (model 1140,
Tanita Corporation, Tokyo, Japan), electronic scale (R160P,
Sartorius AG, Goettingen, Germany), glass syringe (2 ml, Mitsuba,
Tokyo, Japan), heparinized capillary tubes (Scientific Glass, Inc.,
Rockwood, TN, USA), hematology analyzer MEK-6108K (Nihon
Kohden), orbital shaking incubator (Firstek Scientific, Hsin
Chuang, Taiwan, ROC), pH meter (SunTex, Hsi-Chih City, Taipei
County, Taiwan, ROC), pipetman (Gilson, Villiers-le-Bel, France),
pipette tips (Costar), rat oral needle (Klappenecker,
Energiestrasse, Germany), refrigerated incubator (Hotpack,
Warminster, PA, USA), round head needle for oral administration
(Klappenecker), stainless steel scissors (Klappenecker) and
stainless steel forceps (Klappenecker).
Assay for protection by Essiac
®
from ethanol-induced gastric
ulceration. The assay was performed according to the method
described by Robert and colleagues (10). The test substance was
administered orally (p.o.) to a group of three Wistar-derived male,
overnight-fasted rats, weighing 200±20 g, 15 minutes before
challenge with absolute ethanol (1 ml/rat) via oral gavage. One
hour later, the animals were sacrificed and gastric ulceration was
scored for the degree of hemorrhage and severity of ulcerative
lesions, based on the following scoring system: 0 = no hyperemia
or lesions (dark red blood clot), 1 = hyperemia, 2 = one or two
slight lesions, 3 = more than two slight lesions, 4 = more than two
lesions or severe lesions. A reduction of the concurrent control
score values by 50% or more was considered significant.
Assay for serum glucose measurement post glucose-load after Essiac
®
ingestion. The assay was performed according to the method
described by Ho and Aranda (11). Four groups of five ICR-
derived male mice, weighing 22±2 g, were used. The test
substance at doses of 0.4 ml/kg and 4 ml/kg, the vehicle (0.9%
NaCl, 10 ml/kg), or the positive control Glibenclamide at 1 mg/kg
was administered p.o. to overnight-fasted mice 30 minutes before
glucose loading (1 g/kg, subcutaneously (s.c.)). Blood samples
from the orbital sinus were obtained 90 minutes after
administration of the vehicle and/or test substances. The serum
glucose levels were measured by an enzymatic method
(Matarotase-Glucose Oxidase) in samples generated from blood
collected via the orbital sinus of each animal. A reduction of
serum glucose by 20% or more relative to the vehicle-treated
control animals indicated significant activity.
Assay for protection from hepatic injury from carbon tetrachloride
exposure after Essiac
®
ingestion. The assay was performed
according to the method described by Abe and colleagues (12).
The test substance and vehicle were administered p.o. to groups
of five Wistar-derived male rats, weighing 200±20 g, at 30
minutes before, and 4 and 8 hours after challenge with carbon
tetrachloride (CCl
4
, 0.5 ml/kg in olive oil/1:1, p.o.). The animals
were sacrificed 24 hours after the administration of CCl
4
and the
ALT and AST levels were measured by an optimized UV method
with a HITACHI automatic analyzer (model 7050). A reduction
in ALT or AST activity by 30% or more relative to the vehicle-
treated control animals indicated significant hepatic protection.
In addition, the liver and body weights were recorded and
calculated (g liver/100 g body weight) as a reference parameter
for hepatotoxicity.
Assay to assess the effect on cellular immune stimulation after
Essiac
®
ingestion. The assay was performed according to the
method described by Griswold, DiLorenzo and Calabresi (13).
Four groups of five BALB/c male mice, weighing 23±2 g, were
used. The pre-shaven abdomens of the test animals were sensitized
by application of 50 ml of 2.5% oxazolone solution dissolved in
acetone. The test substance and vehicle (0.9% NaCl) were
administered p.o. 1 hour before 2.5% oxazolone sensitization was
performed. The positive control lipopolysaccharide (0.3 mg/kg)
was administered intra-peritoneally (i.p.) at the same time as the
test compound. Eight days later, the animals were challenged with
a second application of oxazolone (2% in 25 ml acetone) to the
right ear. Twenty-four hours later, the ear thickness of each mouse
was measured with a Dyer Model micrometer gauge. A 30% or
more increase in ear swelling relative to the vehicle control was
considered physiologically significant and indicated possible
immunostimulatory activity.
ANTICANCER RESEARCH 26: 3057-3064 (2006)
3058
Assay for the effect on humoral immune stimulation. The assay was
performed according to the method described by Roitt (14). Three
groups of five BALB/c male mice, weighing 22±2 g, were used.
The test animals were sensitized with an intravenous (i.v.)
injection of rabbit red blood cells (RRBC, 10
8
cells in 0.2 ml PBS
/ mouse). The test substance at 0.4 ml/kg and 4 ml/kg and the
vehicle (0.9% NaCl) were administered p.o. to the test animals 72,
48 and 2 hours before sensitization with RRBC. On the ninth day
following sensitization, blood samples were withdrawn from the
orbital sinus and the sera heat-inactivated at 56ÆC for 30 minutes.
Fifty ml of the complement-inactivated serum was then serially
diluted two-fold with 50 ml PBS. Fifty Ìl of this diluted mixture
was added to each well of a 96-well microtiter plate. Thirty Ìl of
2.5% Guinea pig serum (providing complement proteins) in PBS,
150 Ìl of PBS and 20 Ìl of RRBC (10
7
cells) in PBS were added
into the serially-diluted sample serum in each well to yield a final
volume of 250 Ìl/per well. The serum titer was expressed as the
reciprocal of dilution exhibiting hemolysis. A serum titer of 256 or
more was considered significant and indicated possible
immunostimulatory activity.
Results
Essiac
®
was administered p.o. to the test subjects prior to all
experiments. The dosage of Essiac
®
administered in all assays
was calculated on a per weight basis, based upon the
recommendations of the supplier. A dose ten-fold higher than
the recommended dose was included with the recommended
dose in order to assess for a dose-response relationship.
Within these parameters, Essiac
®
at a concentration of
4 ml/kg, but not 0.4 ml/kg, resulted in a 33% inhibition in the
ulceration score compared to the control group in the ethanol-
induced gastric ulceration assay (Table I). The positive
control, the synthetic liquorice derivative carbenoxolone,
produced a 75% inhibition in the gastric ulceration model.
In the Wistar rat model of CCl
4
-induced hepatocyte
injury, administration of Essiac
®
at both the higher and
lower concentrations did not offer any statistically
significant protective effect against hepatocyte damage, as
measured by elevation in the serum transaminase levels
(Table II). However, the higher concentration (4 mg/ml) of
Essiac
®
did decrease the elevation in AST and ALT
observed upon CCl
4
challenge by approximately 5% over
the vehicle control alone, though this result was not
statistically significant.
Essiac
®
, at both concentrations tested, did not
significantly alter the glycemic response to a glucose load
after an overnight fast in the ICR mouse model (Table III).
Upon challenge with 1 g/kg of glucose, Essiac
®
administered at both 0.4 ml/kg and 4 ml/kg resulted in non-
significant increases in the measured serum glucose of 7%
and 3%, respectively. In comparison, the antihyperglycemic
sulfonylurea, glibenclamide, decreased the observed
glycemic response by 30% in the same model.
Leonard et al: In Vivo Analysis of Essiac
®
3059
Table I. Assay for protection by Essiac
®
from ethanol-induced gastric ulceration.
Ulceration score
Treatment Route Dose No. No. of ulcers Total % Inhibition
Vehicle (0.9%NaCl) p.o. 10 ml/kg 1 4
24
34
12 0
Essiac
®
Liquid Extract p.o. 4 ml/kg 1 2
23
33
833
p.o. 0.4 ml/kg 1 4
24
34
12 0
Carbenoxolone p.o. 300 mg/kg 1 1
21
31
3 (75)
The vehicle or test substance was administered orally (p.o.) 15 minutes before oral gavage with absolute ethanol (1 ml/rat). Ulceration was
measured and scored 1 hour later for degree of hemorrhage and severity of ulcerative lesions as follows: 0 = no hyperemia or lesions (dark red
blood clot), 1 = hyperemia, 2 = one or two slight lesions, 3 = more than two slight lesions, 4 = more than two lesions or severe lesions. The
reduction of the concurrent control score values by 50% or more, indicated in parenthesis, was considered significant.
Essiac
®
, at both the lower and higher doses, did not
significantly modulate the cellular immune response as
measured by ear thickness in the oxazolone challenge test
(Table IV). Neither did Essiac
®
, at both concentrations,
significantly affect the humoral immune response, as
measured by serum titer to the RRBC challenge (Table V).
However, in both immunomodulatory assays there was a
trend towards a reduction in the immune response after
administration of Essiac
®
.
Discussion
Cancer patients commonly use Essiac
®
, however, very little
information is available regarding its potential role as an
anticancer agent or cancer supportive agent. This report
presents the first peer-reviewed data regarding the effects
of the polyherbal compound Essiac
®
in an in vivo model
and, thus, provides a reference point from which to direct
future investigations.
ANTICANCER RESEARCH 26: 3057-3064 (2006)
3060
Table II. Assay for protection from hepatic injury from carbon tetrachloride exposure after Essiac
®
ingestion.
ALT AST
Treatment Route Dose No. U/L % Decrease U/L % Decrease
Blank normal control p.o. 10 ml/kg 1 46 171
(Non-CCl
4
-induced) 2 55 158
3 47 133
4 40 121
5 39 116
45.4±2.9 – – 139.8±10.7 – –
Vehicle (0.9% NaCl) p.o. 10 ml/kg 1 1132 2188
(With CCl
4
-induced) 2 912 1776
3 924 1740
4 1772 2920
5 1712 3152
1290.4±188.7 0 2355.2 ±291.2 0
Essiac
®
Liquid Extract p.o. 4 ml/kg 1 1036 2356
2 1632 2812
3 1440 2528
4 1068 1972
5 936 1576
1222.4±133.4 5 2248.8 ±216.3 5
p.o. 0.4 ml/kg 1 988 1928
2 1668 2940
3 1720 3156
4 1012 2232
5 988 1860
1275.2±171.2 1 2423.2 ±264.9 –3
Silymarin p.o. 300 mg/kg 1 408 976
2 836 1664
3 840 2012
4 736 1188
5 688 1128
701.6±79.0 (46) 1393.6±192.7 (41)
The test substances and vehicle were each administered orally (p.o.) at 30 minutes before, and 4 and 8 hours after challenge with a single dose of
CCl
4
(0.5 ml/kg in olive oil/1:1, p.o.). Silymarin was used as a positive control agent and was administered to the test animals, following the same
time schedule. The rats were sacrificed 24 hours after CCl
4
administration and the ALT and AST values were determined. A reduction of the
ALT or AST by 30% or more relative to the vehicle group was considered to be physiologically significant. Negative sign (–) indicates increase
relative to the vehicle control group.
The classic and principal limitation of this experimental
study consisted of the use of a rodent model for in vivo
analysis of Essiac
®
administration and physiological activity.
It is well-established that drug and compound metabolism
are highly species-specific and, thus, the amount and type
of active metabolite(s) available in an animal model will be,
at least partly, dependent on the species used (15). As such,
extrapolation of these results to the clinical arena is only
tentative. Another major limitation of the present study is
the fact that Essiac
®
is often taken over an extended period
of time. The one-time administration incorporated in our
experimental design may not adequately reflect the effects
of repeated administration of Essiac
®
, a dosage schedule
that oncology patients would presumably follow. Our data
does, however, provide initial and immediate results on the
effect of Essiac
®
administration and future research could
attempt to address this unexplored parameter of its use.
To determine whether a dose-response relationship
existed, as well as to mitigate against the possibility that the
recommended dose is too low, we included a dose ten times
the recommended dosage. Within these preliminary
parameters, there appeared to be some indication of a dose-
response trend in much of the data. Further, these trends
were somewhat reflective of the known physiological
activities of the constituent herbs found in Essiac
®
. This
strengthens the validity of our experimental approach. It is
possible that a dose regimen between the recommended
dose and the ten-fold dose may be more effective, however,
this seems unlikely given the relatively small
pharmacological difference in the doses used.
Essiac
®
seemed to afford limited cytoprotection to the
gastric mucosa when administered p.o., an observation
consistent with a similar effect observed with the Essiac
®
-
like compound Flor-Essence
®
(6). It should be noted that
adaptive cytoprotection is non-specifically induced by mild
irritants in this gastroprotective model (16). It was unclear,
from the present results, whether the mechanism of
response elicited by Essiac
®
is specifically cytoprotective or
the result of an adaptive cytoprotective response. Thus,
though p.o. administration of Essiac
®
appeared to be
cytoprotective, further investigation would help to define
the mechanism of cytoprotection more clearly and identify
which, if any, of the specific herbal components are
responsible for this effect.
Leonard et al: In Vivo Analysis of Essiac
®
3061
Table III. Assay for serum glucose measurement post glucose-load after Essiac
®
ingestion.
Treatment Route Dose NÔ. Serum glucose (mg/dl) % Decrease
Vehicle (0.9% NaCl) p.o. 10 ml/kg 1 173
2 171
3 181
4 170
5 160
171.0±3.4 0
Essiac
®
Liquid Extract p.o. 4 ml/kg 1 176
2 166
3 192
4 170
5 180
176.8±4.5 –3
p.o. 0.4 ml/kg 1 172
2 185
3 183
4 195
5 181
183.2±3.7 –7
Glibenclamide p.o. 1 mg/kg 1 130
2 112
3 127
4 121
5 108
119.6±4.2 (30)
The test substance and vehicle, as well as glibenclamide, were administered orally (p.o.) to fasted mice 30 minutes before glucose loading (1 g/kg,
s.c.), and blood samples were obtained 90 minutes later. A reduction of the serum glucose by 20% or more relative to the vehicle-treated control
animals indicated significant physiological activity.
In the Wistar rat model, the administration of Essiac
®
demonstrated a non-significant trend towards hepato-
protection, a finding consistent with previous studies
performed in a rat model using samples of a component herb,
Arctium lappa. The hepatoprotective effect of Arctium lappa
against CCl
4
hepatotoxicity may be mediated by the
substantial free radical scavenging properties of this herb (17).
Previous experimental data in the diabetic mouse model
indicate that the consumption of Arctium lappa aggravated the
serum glucose levels (18). This is in contrast to the observations
ANTICANCER RESEARCH 26: 3057-3064 (2006)
3062
Table IV. Assay to assess the effect on cellular immune modulation after Essiac
®
ingestion.
Ear Thickness (x 0.01 mm, X±SEM)
Treatment Route Dose No. R. Ear L. Ear Net % Increase
Vehicle (0.9% NaCl) p.o. 10 ml/kg 1 32 22 10
2 25 21 4
3 27 23 4
4 28 22 6
5 26 21 5
27.6±1.2 21.8±0.4 5.8±1.1 - -
Essiac
®
Liquid Extract p.o. 4 ml/kg 1 25 21 4
2 33 23 10
3 25 21 4
4 29 22 7
5 24 21 3
27.2±1.7 21.6±0.4 5.6±1.3 -3
p.o. 0.4 ml/kg 1 30 21 9
2 28 22 6
3 24 21 3
4 27 21 6
5 25 21 4
26.8±1.1 21.2±0.2 5.6±1.0 -3
Lipopolysaccharide i.p. 0.3 mg/kg 1 36 22 14
(E. coli LPS) 2 28 21 7
3 32 22 10
4 30 21 9
5 32 21 11
31.6±1.3 21.4±0.2 10.2±1.2 (76)
The test substance and vehicle (0.9% NaCl) were administered p.o. to test animals 1 hour before sensitization was performed with oxazolone 2.5%
in 50 Ìl acetone. The positive control lipopolysaccharide (0.3 mg/kg, i.p. was given, following the same time schedule. Eight days later, the animals
were challenged with a second application of oxazolone and the ear thickness was measured 24 hours later. A 30% or greater enhancement relative
to the vehicle-treated control was considered to be physiologically significant.
Table V. Assay for the effect on humoral immune stimulation.
Serum titer (reciprocal serum dilution)
Treatment Route Dose No. Individual serum Pool serum
Vehicle (0.9% NaCl) p.o. 10 ml/kg 5 256 128 128 128 128 128
Essiac
®
Liquid Extract p.o. 4 ml/kg 5 128 128 64 128 128 128
p.o. 0.4 ml/kg 5 128 128 64 64 128 128
The test substance and vehicle (0.9% NaCl) were administered orally (p.o.) to test animals at 72, 48 and 2 hours before sensitization with rabbit
red blood cells (RRBC). The blood samples were collected 9 days after sensitization and the sera were 2-fold serially diluted and titrated with fresh
RRBC (antigen) and complement (Guinea pig serum) in a 96-well microtiter plate; the hemolysis titer was measured by visual read-out. The
serum titer was expressed as the reciprocal of dilution exhibiting hemolysis
shown here, with Essiac
®
having no mitigating effect on the
glycemic response. However, our model differed from the
previous study as it involved animals with a presumably
physiologically normal response to glucose challenge. Given the
potential for the long-term use of Essiac
®
, it would be prudent
for any clinical study design to incorporate measurement of the
effects on glycemic control to help clarify these findings.
Essiac
®
and Essiac
®
-like products are thought to possess
significant ability to modulate the immune response. However,
oral administration of Essiac
®
in our experimental models did
not significantly alter the in vivo cellular or humoral immune
response. As in the previous results, the trend at both
concentrations in both assays, though not significant, was
consistently towards a reduction in inflammation versus the
vehicle control.
In summary, to address the paucity of peer-reviewed in vivo
research regarding the herbal compound Essiac
®
, we
conducted initial investigations into several of its purported
medicinal properties. The results indicated that Essiac
®
,
administered p.o. at the test concentrations chosen, did not
induce any significant effects in the rat model of hepatic
protection, nor did it induce any significant effect in the
murine models of hypoglycemia. This also applied to cellular
and humoral immunomodulation. Essiac
®
did, however, show
a moderate gastroprotective effect from ethanol-induced
ulceration, although it is, as yet, unclear if this was a specific
or an adaptive cytoprotective response.
Though we acknowledge several limitations to this preliminary
study, these findings are significant in that they provide a base of
scientific knowledge about the in vivo effects of Essiac
®
consumption from which future investigations can be directed.
Specifically, the nature of the gastroprotective response, as well
as the cumulative effects of prolonged Essiac
®
consumption on
modulation of the immune system, are newly identified questions
that may be of interest to cancer patients and clinicians. In light
of the recent study showing a potential detrimental effect of Flor-
Essence
®
in a mammary tumor model (9), as well as an in vitro
study indicating potential in vitro stimulation of human breast
cancer cells with both Essiac
®
and Flor-Essence
®
(19), a study
looking at the in vivo effects of Essiac
®
on tumor cells would be
of obvious significance. This study represents the first published
report on the effects of Essiac
®
consumption in an in vivo model
and has begun to address the paucity of data on this extensively
used herbal compound.
References
1 Ashikaga T, Bosompra K, O'Brien P and Nelson L: Use of
complementary and alternative medicine by breast cancer
patients: prevalence, patterns and communication with
physicians. Support Care Cancer 10: 542-548, 2002.
2 Boon H, Stewart M, Kennard MA et al: Use of complementary/
alternative medicine by breast cancer survivors in Ontario:
prevalence and perceptions. J Clin Oncol 18: 2515-2521, 2000.
3 Richardson MA, Sanders T, Palmer JL, Greisinger A and
Singletary SE: Complementary/alternative medicine use in a
comprehensive cancer center and the implications for oncology.
J Clin Oncol 18: 2505-2514, 2000.
4 Gray RE, Greenberg M, Fitch M, Parry N, Douglas MS and
Labrecque M: Perspectives of cancer survivors interested in
unconventional therapies. J Psychosoc Oncol 15: 149-171, 1998.
5 Fraser SS and Allen C: Could Essiac
®
halt cancer?
Homemaker's Magazine Summer: 9-42, 1977.
6 Tamayo C, Richardson MA, Diamond S and Skoda I: The
chemistry and biological activity of herbs used in Flor-Essence
®
herbal tonic and Essiac
®
. Phytother Res: 1-14, 2000.
7 Kaegi E: Unconventional therapies for cancer: 1. Essiac. The
Task Force on Alternative Therapies of the Canadian Breast
Cancer Research Initiative. CMAJ 158: 897-902, 1998.
8 US Congress OTA: Unconventional Cancer Treatments.
Washington, D.C.: US Government Printing Office, pp. 71-75,
1990.
9 Bennett LM, Montgomery JL, Steinberg SM and Kulp KS:
Flor-Essence
®
herbal tonic does not inhibit mammary tumor
development in Sprague Dawley rats. Breast Cancer Res Treat
88: 87-93, 2004.
10 Robert A, Nezamis JE, Lancaster C and Hanchar AJ:
Cytoprotection by prostaglandins in rats. Prevention of gastric
necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl,
and thermal injury. Gastroenterology 77: 433-443, 1979.
11 Ho RS and Aranda CG: The influence of 2,2-dimethyl-1(4-
methylphenyl)-1-propanone (SaH50-283) on food efficiency in
rats. Arch Int Pharmacodyn 237: 98-109, 1979.
12 Abe H, Sakaguchi M, Odashima S and Arichi S: Protective
effect of saikosaponin-d isolated from Bupleurum falcatum L.
on CCl
4
-induced liver injury in the rat. Naunyn-Schmiedberg's
Arch Pharmacol 320: 266-271, 1982.
13 Griswold DE, DiLorenzo JA and Calabresi P: Quantification
and pharmacological dissection of oxazolone-induced contact
sensitivity in the mouse. Cell Immunol 11: 198-204, 1974.
14 Riott I: Immunological Tests in Immunology. London: Mosby
Publishing, pp. 25.1-25.4, 1993.
15 Szotakova B, Baliharova V, Lamka J et al: Comparison of in
vitro activities of biotransformation enzymes in pig, cattle, goat
and sheep. Res Vet Sci 76: 43-51, 2004.
16 Robert A, Nezamis JE, Lancaster C, Davis JP, Field SO and
Hanchar AJ: Mild irritants prevent gastric necrosis through
"adaptive cytoprotection" mediated by prostaglandins. Am J
Physiol 245: 113-121, 1983.
17 Lin CC, Lu JM, Yang JJ, Chuang SC and Ujiie T: Anti-
inflammatory and radical scavenge effects of Arctium lappa. Am
J Chin Med 24: 127-137, 1996.
18 Swanston-Flatt SK, Day C, Flatt PR, Gould BJ and Bailey CJ:
Glycaemic effects of traditional European plant treatments for
diabetes. Studies in normal and streptozotocin diabetic mice.
Diabetes Res 10: 69-73, 1989.
19 Kulp KS, Montgomery JL, Nelson DO et al: Essiac
®
and Flor-
Essence
®
herbal tonics stimulate the in vitro growth of human
breast cancer cells. Breast Cancer Res Treat. Mar 16, 2006
[Epubl ahead of print].
Received January 30, 2006
Revised May 11, 2006
Accepted May 23, 2006
Leonard et al: In Vivo Analysis of Essiac
®
3063
