Food Sci Tech goutweed for the correction of the lipid metabolism disorders

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Нутриціологія, дієтологія, проблеми харчування
Харчова наука і технологія 9 Volume 11 Issue 4/ 2017
UDC 615.272/451.16:641.561/563:582.893:612.397.2
GOUTWEED (Aegopodium podagraria L.) BIOLOGICAL ACTIVITY
AND THE POSSIBILITIES OF ITS USE FOR THE CORRECTION OF THE LIPID
METABOLISM DISORDERS
O. Tovchiga, Ph.D., Ass. Prof.*/***, E-mail: farmacol@nuph.edu.ua
O. Koyro, Ph.D.*, E-mail: farmacol@nuph.edu.ua
S. Stepanova, Ph.D., Ass. Prof.**, E-mail: bromatology@nuph.edu.ua
S. Shtrygol’, Prof. Dr. of Medicine*/***, E-mail: farmacol@nuph.edu.ua
V. Evlash, , Prof. Dr. of Technology****, E-mail: chem_mikro@hduht.edu.ua
V. Gorban’, Ph.D., Ass.Prof.****, E-mail: chem_mikro@hduht.edu.ua
T. Yudkevich, researcher***, E-mail: cndl@nuph.edu.ua
*department of pharmacology, **department of nutriciology and pharmaceutical bromatology
***Central scientific-research laboratory
National University of Pharmacy, 53 Pushinskaya str., Kharkiv, 61002, Ukraine
****department of chemistry, microbiology and food hygiene
Kharkiv State University of Food Technology and Trade, 53 Klochkivska str., Kharkiv, 61051, Ukraine
Abstract. The article summarizes data concerning the biological activity of the promising herbal raw material: aerial part
of goutweed (Aegopodium podagraria L., Apiaceae). This plant since time immemorial has been used as vegetable and fodder plant
as well as in folk medicine including the treatment of the metabolic disorders. Nowadays the interest in this plant increases. The
technology of obtaining the extract and the tincture from goutweed aerial part is described, the chemical composition of these
preparations is elucidated. Pharmacological effects of the preparations obtained from goutweed are characterized with the special
emphasis on the possibilities of the lipid metabolism disorders correction and prevention. The presented experimental results
substantiate the efficacy of goutweed extract and the tincture under the conditions of alimentary lipemia together with their safety in
the intact animals. Thus, the hypolipidemic activity of goutweed extract (1 g/kg intragastrically) and goutweed tincture (1 cm3/kg
intragastrically) was shown in the test with olive oil loading in rats. The extract appeared to be able to decrease significantly the
level of triglycerides in blood plasma, while the tincture reduced the content of plasma total lipids. In the intact rats, the extract at
doses of 100 mg/kg and 1 g/kg as well as the tincture at doses of 1 and 5 cm3/kg did not influence on the values of the lipid
metabolism after 12 days of administration. Total and HDL cholesterol as well as atherogenic index and plasma total lipids level
remained unchanged. In contast to the data previously obtained on the models of hyperuricemia, in the intact rats there were no
changes in plasma uric acid concentration (which was determined proceeding from the role of the purine metabolism disorders in
metabolic syndrome pathogenesis). Thus, goutweed preparations are characterized with the regulatory mode of action and sufficient
level of safety. The development of drugs as well as functional foods containing goutweed herbal raw material is promising.
Keywords: goutweed (Aegopodium podagraria L.), herbal raw material, herbal drugs, lipid metabolism, functional foods.
БІОЛОГІЧНА АКТИВНІСТЬ ЯГЛИЦІ ЗВИЧАЙНОЇ (Aegopodium podagraria L.)
ТА МОЖЛИВОСТІ ЇЇ ЗАСТОСУВАННЯ ДЛЯ КОРЕКЦІЇ ПОРУШЕНЬ
ОБМІНУ ЛІПІДІВ
О.В. Товчига, к.фарм.н., доцент*/***, E-mail: farmacol@nuph.edu.ua
О.О. Койро, к.фарм.н.*, E-mail: farmacol@nuph.edu.ua
С.І. Степанова, к.фарм.н., доцент**, E-mail: bromatology@nuph.edu.ua
С.Ю. Штриголь, д.мед.н., професор*/***, E-mail: farmacol@nuph.edu.ua
В.В. Євлаш, д.техн.н., професор****, E-mail: chem_mikro@hduht.edu.ua
В.Г. Горбань , к.техн.н., доцент****, E-mail: chem_mikro@hduht.edu.ua
Т.К. Юдкевич, н.с.***, E-mail: cndl@nuph.edu.ua
*кафедра фармакології, **кафедра нутріциології та фармацевтичної броматології,
***Центральна науково-дослідна лабораторія
Національний фармацевтичний університет, вул. Пушкінська, 53, м. Харків, 61002
****кафедра хімії, мікробіології та гігієни харчування
Харківський державний університет харчування та торгівлі, вул. Клочківська, 333, м. Харків, 61051
Анотація. У статті узагальнено відомості щодо біологічної активності перспективної рослинної сировини:
надземної частини яглиці звичайної (Aegopodium podagraria L., Apiaceae). Висвітлено технологію одержання препаратів із
цієї рослинної сировини, охарактеризовано їхій хімічний склад та фармакологічні ефекти, особливу увагу приділено
можливостям корекції порушень обміну ліпідів та їхньої профілактики. Наведено експериментальні дані, які
підтверджують ефективність екстракту та настойки яглиці звичайної в умовах аліментарної ліпемії поряд із їх безпечністю
в інтактних тварин. Так, гіполіпідемічна активність екстракту яглиці (1 г/кг внутрішньошлунково) та настойки яглиці
(1 см3/кг внутрішньошлунково) була встановлена на щурах у тесті із навантаженням оливковою олією. У інтактних щурів
екстракт у дозах 100 мг/кг та 1 г/кг, а також настойка у дозах 1 та 5 см3/кг не впливають на показники обміну ліпідів після
12-денного введення. Створення лікарських препаратів, а також дієтичних добавок або функціональних харчових
продуктів на основі сировини яглиці звичайної є перспективним.
Ключові слова: яглиця звичайна (Aegopodium podagraria L.), рослинна сировина, лікарські препарати
рослинного походження, обмін ліпідів, дієтичні добавки, функціональні харчові продукти.
DOI: http://dx.doi.org/10.15673/fst.v11i4.726

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Харчова наука і технологія 10 Volume 11 Issue 4/ 2017
Introduction. Formulation of the problem
There is a growing demand for herbal products
nowadays, both in the field of drug development and in
the region of functional foods and dietary supplements
production for health promotion and disease risk
reduction. The complex composition of a crude herbal
raw material is a prerequisite of diverse biological
activities including favourable metabolic effects. At
the same time, the possible toxic influence or
disadvantageous interactions with the drugs or food
simultaneously taken are possible. These substantiates
a need in a scientific verification of the effects of the
miedicinal herbs as well as the drugs of functional
foods of plant origin.
Our efforts are focused on the pharmacological
studies of the preparations obtained from the aerial part
of goutweed (Aegopodium podagraria L., Apiaceae). It
is a an ubiquitous perennial plant widely used in
traditional medicine and consumed as vegetable or
fodder plant. Dry extract and tincture obtained from
goutweed are standardized on hydroxycinnamic acids
content, have a low toxicity level and are able to
normalize metabolic processes and to protect the liver
and the kidney under the different experimental
conditions.
Analysis of recent research and publications
Biological activity of Aegopodium
podagraria L. Aegopodium podagraria L since time
immemorial has been used in traditional medicine for
the treatment of rheumatism, kidney and bladder
diseases, gastrointestinal and metabolic disorders
including gout and related states [1–6]. The low
toxicity level of goutweed preparations, which is
expected considering its use as vegetable and fodder
plant, has been confirmed experimentally for water
extract and the tincture obtained from the aerial part of
the plant [7].
The valuable pharmacological effects of
goutweed preparations have been established recently.
The extract and the tincture obtained from its aerial
part exert nephro- and hepatoprotective effects [7–9].
Goutweed extract is especially effective in protection
of the kidney against the different damaging factors,
including ischemia, myoglobinemia, gentamicin,
ethylene glycole, carbon tetrachloride. It prevents
lethality and kidney histostructure changes, normalizes
the kidney concentration function, reduces proteinuria
and hyperazotemia. It restores the excretory renal
function depending on the conditions of the kidney
functioning (supporting urine-concentrating ability or
normalizing the excretory capacities after water
loading), and does not lead to hyperkalemia (even in
the animals with the disturbed renal function) despite
the high potassium content [10–11]. As to the active
components of goutweed leaves extract, it has been
shown that leaves protein-polysaccharide complex, and
flavonoid trifolin exert significant nephroprotective
activity reducing lethality, hyperazotemia and
proteinuria, eliminating anuria, counteracting
glomerular filtration decrease, normalizing
histopathological kidney structure [10].
The protective multitargeted action of goutweed
drugs was also confirmed in regard to the liver injury.
The leaves extract, leaves protein-polysaccharide
complex, and trifolin were the most effective
hepatoprotective agents that improved survival rate,
suppressed cytolysis and lipid peroxidation, activated
antioxidative system, maintained liver glycogen and
protein synthesis [10]. Besides, goutweed aerial part
water-ethanol extract has been shown to exert a
hepatoprotective effect in animals treated with the
complex of antitumor drugs [12].
The preparations obtained from Aegopodium
podagraria L. are also characterized by favourable
metabolic effects including antidiabetic activity. In has
been confirmed in alloxan-induced diabetic mice, in
which goutweed tincture (1 and 5 cm3/kg) as well as
the extract (1 g/kg) reduce glycemia after a course
treatment and normalize blood uric acid level. The
extract also demonstrates hypoazotemic effect, realized
through extrarenal mechanisms, and counteracts body
mass decrease [13].
Normalizing influence of goutweed tincture
(1 cm3/kg) on glycemia level in rats is also evident
when the metabolic disorders are induced by excess
fructose combined with hydrochlorothiazide. The
extract (1 g/kg) effect under these conditions exerts a
hypouricemic. When further elevation of uricemia is
induced in such animals by potassium oxonate,
goutweed preparations contribute to diuresis
maintenance. Both the extract and the tincture (5
ml/kg) tend to increase sodium reabsorption
(spontaneous diuresis method) reduced by fructose
excess (per se or combined with hydrochlorothiazide).
The extract and the tincture (1 cm3/kg) demonstrate
antiproteinuric effect in water-loading test [14,15].
Aegopodium podagraria L. tincture appeared to
be especially effective for the correction of the
disturbances in carbohydrate metabolism. Recently we
have substantiated the expediency of its combining with
metformin as the widely prescribed first line agent of the
peroral normoglycemic drugs. In dexamethasone-treated
rats (high dose of 5 mg/kg inducing severe disorders of
metabolism was used) the tincture (1 ml/kg) partially
increases the efficacy of metformin (50 mg/kg).
Goutweed tincture demonstrates a permissive effect on
the action of metformin in regard to glucose and lipid
metabolism normalization, the reduction in plasma ALT
activity and increment in urea clearance as well as
normalization of plasma ALP activity [16,17]. On the
model of the primary disorders of the lipid metabolism
in rats (administration of protamine sulfate against the
background of atherogenic diet) the tincture also shows
an ability to increase metformin efficacy: these drugs in
combination, but not per se, completely normalize area
under glucose curve in the glucose tolerance test [18].

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It is notable that the hypoglycemic effect of
Aegopodium podagraria L. tincture in intact rats is
moderate with glycemia values staying within the
normal physiological range. Goutweed tincture exerts
hypoglycemic action in intact rats after the
administration of single doses of 0.5; 1.0; 5.0 cm3/kg
under the conditions of glucose load. Basal glycemia
tends toward the reduction in animals receiving the
tincture at doses of 0.50 and 2.5
cm3/kg and is
significantly decreased after its administration at a dose
of 1 cm3/kg [19]. After course administration of this
preparation, a statistically significant decrease in basal
glycemia and area under the glycemic curve is seen at
a dose of 5 cm3/kg [8].
The safety of combined use of Aegopodium
podagraria L. tincture with metformin was verified in
the intact rat and it was shown that the tincture at doses
of 0.5 and 1.0 cm3/kg does not block the effects of
metformin, and does not enhance its effect with the
excessive decrease of blood glucose concentration (at
low doses of metformin some indices of
synergoantagonism are seen). In the glucose tolerance
test, the tincture at a dose of 1.0 ml/kg (but not
0.5 ml/kg) co-administered with metformin allows
decreasing its effective dose [19].
Goutweed preparations do not increase risk of
ethanol-induced hypoglycemia. In rats receiving a
single dose of ethanol (9 g/kg intragastrically), in
which hypoglycemia was not manifested, but the
tendency to the exhaustion of liver glycogen was seen,
the tincture, on the contrary, increased glycemia, while
glycogen reserves did not undergo exhaustion (the
changes in same direction were registered in rats
receiving fenofibrate) [20]. Thus, the tincture may be
characterised as a preparation possessing the sufficient
level of safety and not inducing hypoglycemia.
Other favourable metabolic effects of goutweed
drugs are also manifested in ethanol intoxication,
adiitionally confirming their ability to decrease
xenobiotics toxicity described above. It has been
shown that the extract (1 g/kg but not 100 mg/kg)
significantly reduces the duration of ethanol-induced
narcosis in mice [21,22]. In rats receiving a single dose
of ethanol the extract (100 mg/kg and 1 g/kg) and the
tincture (5 cm3/kg) normalize the lipid composition of
the liver, surpassing fenofibrate (100 mg/kg) or being
comparable with it. The extract (1 g/kg) reduces ALT
activity, the tincture shows a dose-dependent influence
on γ-glutamyl transferase activity. These do not induce
unfavourable shifts in total protein, albumin, uric acid,
and creatinine content [20,23].
Together with the favourable influence on the
visceral systems, central effects of Aegopodium
podagraria L. are of significant interest taking into
account its planned prolonged usage for the treatment of
chronic diseases of as the component of the functional
foods. Sedative effect is among the properties of this
plant mentioned in traditional medicine [1,3]. The study
of its aerial part extract and tincture in the intact mouse
have shown that they do not induce suppression of the
locomotor activity and exploratory behaviour in the
combined open field test. The extract is able to decrease
the levels of depression under certain conditions (at a
dose of 100 mg/kg but not at a dose of 1 g/kg in female
mice that is accompanied with the worsening of the
results of the passive avoidance test). Against the
background of this dose, another useful effect is evident,
such as the reduction of the anxiety signs in the animals
of both sexes, in male mice this reduction is also seen
under the influence of the extract at a dose of 1 g/kg and
the tincture at doses of 1 and 5 cm3/kg [24]. Besides, the
same dose of goutweed extract of 100 mg/kg
significantly increases the exhaustive swimming time
(10 % and 20 % load) in male mice. In female mice such
effect is registered with 20 % load against a background
of the extract at both doses. The extract exerts a
moderate positive influence on cognitive functions in
mice (but not in rats) in the extrapolation escape test
without any significant changes in level of depression in
reserpine-treated rats. The central effects of goutweed
tincture are less pronounced [25]. The expected
prolonged usage of goutweed make it necessary to
verify the possible interactions with psychotropic drugs.
In addition to the above-mentioned ability of the extract
to decrease the duration of ethanol-induced narcosis as
the non specific CNS suppressive agent, there are data
concerning goutweed preparations interaction with the
well known drug with higher specifity of the inhibitory
action– thiopental sodium. Namely, goutweed tincture,
in contrast to the extract, significantly reduces the
duration of sleep caused by thiopental sodium in male
mice (at a dose of 1 cm3/kg, but not 5 cm3/kg), being
comparable by this effect with Hypericum perforatum L.
extract (100 mg/kg) [26]. Thus, goutweed extract and
the tincture after course administration do not lead to the
undesirable shifts in CNS functioning and do not
potentiate the action of CNS depressants.
Another important aspect of herbal drugs
pharmacology is their interaction with microorganisms.
Serbian scientists have studied the antibacterial activity
of water, ethanol and ethyl acetate extracts from
Aegopodium podagraria L. and showed that ethanol
extract was the most effective [27], it also exhibited
synergistic and additive effects with streptomycin and
chloramphenicol [28]. Moderate antibacterial and
antifungal properties were reported for methanol
extract [29].
The data available on goutweed aerial part
preparations influence on the lipid metabolism.
Lipid metabolism disorders are involved in the
pathogenesis of diseases of the cardiovascular system,
metabolic syndrome and diabetes mellitus, they can
also arise as a side effect of drugs [30]. The role of
healthy diet in prevention of such disorders is generally
accepted and certain drugs of herbal origin may
become the effective supplementation of their complex
therapy. In this context, flavonoids and
hydroxycinnamic acids attract much attention as the

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possible active components of the functional foods and
herbal drugs [31–32]. As described above, these sub-
substances are present in goutweed raw material.
Table 1 summarizes data of the experimental studies,
which addressed the influence of goutweed aerial part
preparations on the lipid metabolism.
Table 1. Summarised data of the experimental studies elucidating the influence of Aegopodium podagraria
L. aerial part preparations on the lipid metabolism
Model Preparation,
dose, course Effects Refe-
rence
Rats receiving
excess fructose
combined with
hydrochlorothiazide
Aerial part water extract,
1 g/kg, tincture (1 and
5 cm3/kg), course
administration for 10 weeks
Decrease in LDL cholesterol (elevated under the
influence of fructose excess) and normalization of
the atherogenic index (the extract and the tincture at
b
oth doses, as well as hydrochlorothiazide),
increment in HDL cholesterol (the tincture at both
doses and h
y
drochlorothiazide
)
[33]
Rats receiving a
single dose of
ethanol (9 g/kg
intragastrically)
Aerial part water extract,
100 mg/kg and 1 g/kg,
prophy-lactic administration
for 7 da
y
s
Significant reduction of triglycerides and
cholesterol, increment in the content of
p
hospholipids in the liver, lipid metabolism values
of blood
p
lasma do not differ from that of intact rats
[23]
Aerial part tincture, 1 and
5 cm3/kg, prophylactic
administration for 7 days
Decrease in the level of triglycerides and
cholesterol (only at high dose) and increment in the
content of phospholipids in the liver (at both doses),
reduction of the HDL cholesterol (that is similar to
the effect of the reference drug fenofibrate under the
conditions of the stud
y)
[23]
Rats receiving
dexamethasone
(5 mg/kg
subcutaneously for 5
da
y
s
)
Aerial part tincture,
1 cm3/kg for 5 days
(per se or combined with
metformin, 50 mg/kg)
Reduction of triglycerides level in blood plasma and
increment of HDL cholesterol content, the tendency
towards the decrease in total lipids level (the tincture
per se or combined with metformin), decline in LDL
cholesterol content
(
the tincture
p
er se
)
[16]
Rats receiving
protamine sulfate
against the
background of
atherogenic diet and
cholesterol
administ
r
ation
Aerial part water extract
(1 g/kg), tincture (1 cm3/kg),
course administration
for 16 days (per se or
com
b
ined with metformin,
50 mg/kg)
Decrease in the level of triglycerides and
cholesterol and increment in the content of
p
hospholipids in the liver (both preparations and
their combinations with metformin), lipid spectrum
of the blood plasma is not changed significantly by
all drugs
[18]
Phytochemical сomposition of the
preparations obtained from Aegopodium
podagraria L. By the commonly used methods of
phytochemical analysis (qualitative reactions, paper
and thin-layer chromatography), phenolic compounds
such as flavonoids and hydroxycinnamic acids were
identified in both goutweed preparations, while
coumarins were detected in the tincture. Among
phenolic compounds hydroxycinnamic acids prevail.
Chlorogenic acid and caffeic acid were identified
through comparison with authentic samples.
The procedure of hydroxycinnamic acids and
flavonoids quantitative assay by direct
spectrophotometry was successfully applied to
goutweed aerial part [34,35] and to the preparations
obtained from it, the content of hydroxycinnamic acids
(chlorogenic acid equivalent) equalled 5.33±0.07 % in
the extract and 0,36±0,01 % in the tincture 1:5 (if the
plant material and solvent were taken in 1:10 ratio, this
value equalled 0.26±0.03 %), while the content of
flavonoids equalled 0.47±0.02% and <0.02 %
respectively [10,36].
The protein polysaccharide complex of the
aerial part of the plant partially mediates its nephro-,
hepatoprotective and hypouremic activity. Its content
was determined [10,37], and it equalled 28.5±3.0%.
The monomer composition of the protein
polysaccharide complex carbohydrates was studied
using paper chromatography after hydrolysis, which
allowed identifying glucose, galactose, fructose,
arabinose, xylose, rhamnose. The amino acid
composition of the protein polysaccharide complex
was investigated using the methods [38,39]. Aspartic
acid (0.88 %), glutamine (0.70 %), tyrosine (0.55 %),
histidine (0.48 %), methionine (0.45 %), serine
(0.43 %), glycine (0.43 %), isoleucine (0.3 %)
predominate in the protein part of the protein
polysaccharide complex. The content of the basic
amino acids obtained by hydrolysis was also
determined in the goutweed extract. Tyrosine (0.69 %),
methionine (0.5 %), glutamine (0.47 %), aspartic acid
(0.36 %), arginine (0.35 %) histidine (0.34 %) were
predominant among them [10].
In addition, the aerial part of goutweed contains
a significant amount of mineral elements such as
silicon (500 –1140 mg/100 g), phosphorus (190 –
300 mg/100 g), magnesium (420 – 1020 mg/100 g),
calcium (1040 – 2050 mg/100 g), iron (15 –

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95 mg/100 g), copper (0.7 – 4 mg/100 g), zinc (0.05 –
10 mg/100 g) et al. Potassium (3810–8300 mg/100 g)
is the predominant among the macroelements in the
raw material. Its content reaches 60% of the ash
weight. Potassium in a significant amount is trans-
transferred to the extract (from 6000 mg/100 g to
16000 mg/100 g), while its content in the tincture is
much lower and equals 350 mg/100 g. Potassium
supplementation is of high importance, since the
modern population suffer from its deficiency, and its
high content in goutweed raw material contributes to
the activity of the preparations obtained from it
(besides, these preparation are characterized by high
K+/Na+ ratio that, according to the data in the literature,
is specific for herbal drugs able to enhance the
excretory renal function) [10,11,40,41]. At the same
time, it is important that heavy metals concentration
(plumbum, molybdenum, nickel) in goutweed raw
material is low and they are not accumulated [40,41].
The data discussed above confirm the promising
phytochemical composition of goutweed preparations as
well as their high level of safety and significant efficacy
in the disorders of lipid as well as uric acid metabolism.
At the same time, the study of the promising substances
for functional foods and drugs development presupposes
the determination of their effects in the intact animals.
Besides, the changes of the lipid metabolism in the intact
rat receiving goutweed preparations under the conditions
of alimentary lipemia, which is of special interest from
the point of view of nutriciology, are still not described.
The purpose of the experimental part of this
study was to establish the basis for functional foods
and drugs development through the evaluation the
efficacy of goutweed extract and the tincture under the
conditions of alimentary lipemia as well as their safety
in the intact animals.
The following tasks were formulated to achieve
this aim:
1. to determine the influence of the prophylactic
course administration of goutweed extract
(100 mg/kg and 1 g/kg intragastrically) and
goutweed tincture (1 and 5
cm3l/kg
intragastrically) on the blood plasma values of
the lipid metabolism in the test with olive oil
loading in rats (the conditions of the alimentary
lipemia);
2. to study the possible shifts in the lipid
metabolism in the intact rats after the course
administration of goutweed extract (100 mg/kg
and 1 g/kg intragastrically) and goutweed
tincture (1 and 5 cm3/kg intragastrically).
Research Materials and Methods
Plant material and extraction. The aerial parts
of A. podagraria were collected from the natural
population in Kharkiv region (Ukraine) in June. The
herbal raw material was dried at room temperature and
powdered using a standard grinding mill to obtain the
powder with the mean particle size of approximately
2 mm. The powder was twice extracted with water at
90ºC. The plant material and solvent were taken in
1:10 ratio, the solvent volume was increased according
to the swelling index. The extract was filtered under
vacuum conditions and concentrated using a rotary
evaporator, and a dry solid was obtained (residual
water content equalled 5%), corresponding to an
average yield of 25%. Goutweed dry extract is a brown
powder with a characteristic pleasant odour, sour-bitter
to taste.
Goutweed tincture was prepared by double
extraction with 70% ethyl alcohol. The plant material
and solvent were taken in 1:5 ratio, the solvent volume
was increased according to the swelling index. The
solvent was divided into two parts. The plant material
was macerated in 2/3 solvent at room temperature for
five days being periodically shaked and stirred. The
mixture was filtered under vacuum conditions and
maceration process was repeated under the same
conditions with the rest of the solvent. The obtained
liquids were combined into one, kept for two days at
4ºC, filtered and brought to the calculated volume with
the solvent. Goutweed tincture is dark green liquid with
a characteristic odour. The standard technology of A.
podagraria dry extract and tincture obtaining was in
accordance with the requirements of State
Pharmacopoeia of Ukraine and was described
previously [7–9].
The content of the active components, namely
the hydroxycinnamic acids, was measured in the
extract and in the tincture by the direct
spectrophotometry, the data obtained were within the
limits described above.
Noninbred albino rats breeded in the Central
Scientific-Research Laboratory of National University
of Pharmacy (Ukraine) were used. Male rats were
housed in a well-ventilated animal room at a controlled
temperature and relative humidity, on a natural light-
dark cycle. Food and water were supplied ad libitum.
All the experimental protocols were in accordance with
“Directive 2010/63/EU of the European Parliament and
of the Council of 22 September 2010 on the protection
of animals used for scientific purposes.”
The doses of goutweed preparations were
chosen on the basis of previous experiments
confirming their positive metabolic and
organoprotective activity. Herbal preparations were
administered intragastrically once a day. Ethanol was
removed from the tincture before administration. Rats
of the intact control groups received intragastrically tap
water by the similar scheme.
At the first stage of the experiment the values of
the lipid metabolism were determined under the
conditions of alimentary lipemia as described in [33].
The rats (with 200 to 250 g body weight) were
randomised into six groups: intact control (n=7);
hyperlipidemic control (n=8) and and the animals
receiving the extract at doses of 100 mg/kg (n=6) and 1

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g/kg (n=6); the tincture at doses of 1 ml/kg (n=7) and
5 ml/kg (n=8). On day 7 after the administration of the
last dose of the herbal preparations (or water) the rats
received olive oil (qualified “for food purposes”) load-
loading at a dose of 10 g/kg. 8 hours after the blood
samples were obtained from a cut at the tip tail [42]
and blood plasma was separated immediately by
centrifugation (the anticoagulant heparin in vitro).
Total cholesterol content in plasma was determined
using enzymatic methods, plasma total lipids level – by
the reaction with phospho-vanillin reagent with
commercially-available kits (Spine-Lab, Ukraine).
At the second stage of the experiment the values
of the lipid metabolism were determined in the intact
rats (with 160 to 210 g body weight) after 12 day of
goutweed preparations administration. Uric acid
concentration in plasma was also measured in these
animals samples because this value is amond the
targets of goutweed influence, and hyperuricemia is
commonly registered in the patients with metabolic
syndrome, hyperlipidemia and other “diseases of
civilization,” thus it is important to verify the
possibilities of the simultaneous shifts of the values of
the lipid and purine metabolism. In the previous
studies [11] the influence of goutweed preparations on
uric acid exchange in rats was limited to the short
course of administration – up to 3–6 days – and mainly
addressed renal excretion of this metabolite.
Rats were randomly assigned to 5 groups: intact
control (n=9) and the animals receiving the extract at
doses of 100 mg/kg (n=8) and 1 g/kg (n=9); the
tincture at doses of 1 ml/kg (n=7) and 5 cm3/kg (n=8).
On day 12 after the administration of the last dose of
the herbal preparations (or water), blood samples were
obtained and plasma was obtained as described above.
Total cholesterol content in plasma was determined
using enzymatic methods, HDL cholesterol – using
phosphotungstate-Mg2+ precipitation and enzymatic
cholesterol assay, plasma total lipids level– by the
reaction with phospho-vanillin reagent, uric acid
concentration – by the uricase method with
commercially-available kits (Spine-Lab, Ukraine).
Atherogenic index was calculated by using the
following formula: atherogenic index=(total
cholesterol − HDL-C)/HDL-C
Medians, 25% and 75% percentiles (upper and
lower quartiles) were calculated as recommended for
biomedical research. The traditionally used arithmetic
means and their standard errors (M±m) are also given.
The comparison of the central tendencies of
independent samples was performed by the criterion of
Mann-Whitney U.
Results of the research and their discussion
The results of the first stage of the experiments
confirmed a hypolipidemic effect of Aegopodium
podagraria L. that was also partially reported in [33].
As can be seen in Figure 1, the extract at a dose of
1 g/kg (but not 100 mg/kg) significantly reduced
triglycerides content which was noticeably increased
after lipid loading . This value in the animals receiving
the tincture did not differ significantly from
hyperlipemia control group, still the increment in the
dose was not beneficial. The absence of the advantages
of the dose increase was also shown in regard to the
carbohydrate metabolism [13,14].
Median; Box: 25%-75%; Whisker: Non-Outlier Range
***
**^ **##
**
*&^^
123456
0,2
0,4
0,6
0,8
1,0
1,2
1,4
1,6
1,8
2,0
2,2
2,4
2,6
2,8
3,0
3,2
Triglycerides level. mmol/l
Median 25%-75% No n-Outlier Range O utlier s Extremes
Fig. 1. The changes in plasma triglycerides level in rats receiving goutweed drugs
under the conditions of olive oil loading, mmol/dm3
Notes. 1. Intact control; 2. Hyperlipidemia control; 3. Hyperlipidemia + goutweed extract, 100 mg/kg;
4. Hyperlipidemia + goutweed extract, 1 g/kg; 5. Hyperlipidemia + goutweed tincture, 1 cm3/kg; 6.
Hyperlipidemia + goutweed tincture, 5 cm3/kg; * – p<0.05 compared to intact control; ** – p<0.01 compared to
intact control; *** – p<0.001 compared to intact control; ## – p<0.02 compared to the hyperlipemia control group;
^ – p<0.05 compared to the group receiving the extract at a dose of 1 g/kg; ^^ – p<0.02 compared to the group
receiving the extract at a dose of 1 g/kg; & – p<0.05 compared to the group receiving the tincture at a dose of
1 ml/kg.

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Харчова наука і технологія 15 Volume 11 Issue 4/ 2017
A similar pattern was seen in the influence of
goutweed tincture on the total lipids level (Figure 2) –
hypolipidemic effect was eliminated after the incre-
increment in the dose. The influence of goutweed
extract on this value was dose-dependent with the
opposite relationship “dose-effect,” still there were no
statistically significant differences with hyperlipemia
control group value.
Median; Box: 25%-75%; Whisker: Non-Outlier Range
*** ***^&&
*** **#
**
123456
0,0
1,0
2,0
3,0
4,0
5,0
6,0
7,0
8,0
9,0
Total lipids level, g/l
Median 25% -75% Non-Outlier Range Out lie r s Extremes
Fig. 2. The changes in plasma total lipids level in rats receiving goutweed drugs
under the conditions of olive oil loading, g/dm3
Notes. 1) Intact control; 2) Hyperlipidemia control; 3) Hyperlipidemia + goutweed extract, 100 mg/kg;
4) Hyperlipidemia + goutweed extract, 1 g/kg; 5) Hyperlipidemia + goutweed tincture, 1 cm3/kg;
6) Hyperlipidemia + goutweed tincture, 5 cm3/kg; ** – p<0.01 compared to intact control; *** – p<0.001
compared to intact control; # – p<0.05 compared to the hyperlipemia control group; ^ – p<0.05 compared to the
group receiving the extract at a dose of 1 g/kg; && – p<0.02 compared to the group receiving the tincture at a
dose of 1 cm3/kg.
Total cholesterol level (Figure 3) tended
towards decrease in rats receiving the extract at a high
dose and demonstrated inter-individual differences in
animals treated with the tincture at a low dose, so there
were no statistically significant differences with
hyperlipemia control group value.
Median; Box: 25%-75%; Whisker: Non-Outlier Ra nge
*** *
123456
1,5
2,0
2,5
3,0
3,5
4,0
4,5
5,0
5,5
6,0
6,5
Cholesterol level, mmlol/l
Median 25%-75% Non-Outlier Range O utlie r s Extremes
Fig. 3. The changes in plasma total cholesterol level in rats receiving goutweed drugs
under the conditions of olive oil loading, mmol/l
Notes. 1. Intact control; 2. Hyperlipidemia control; 3. Hyperlipidemia + goutweed extract, 100 mg/kg;
4. Hyperlipidemia + goutweed extract, 1 g/kg; 5. Hyperlipidemia + goutweed tincture, 1 cm3/kg; 6.
Hyperlipidemia + goutweed tincture, 5 cm3/kg;* – p<0.05 compared to intact control;
** – p<0.01 compared to intact control

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Харчова наука і технологія 16 Volume 11 Issue 4/ 2017
As shown in Table 2, all investigated prepara-
preparations did not considerably change the
values of the lipid and uric acid metabolism after 12
days of administration to the intact rat. This
confirms their high level of safety which is
necessary for the substances planned to be used as
the components of functional foods or drugs used in
chronic diseases.
Table 2 – Influence of Aegopodium podagraria L. preparations (course administration)
on plasma values of lipid and uric acid metabolism in the intact rats;
Mean ± S.E.M; Q50 (Q25–Q75), n=6–9
Indicators Intact control
Goutweed
extract,
100 mg/kg
Goutweed
extract, 1 g/kg
Goutweed
tincture, 1 cm3/kg
Goutweed tincture,
5 cm3/kg
Total
cholesterol,
mmol/dm3
1.75±0.16
1.84
(1.34–2.01)
1.90±0.21
1.94
(1.59–2.31)
1.85±0.15
1.85
(1.76–2.08)
2.01±0.13
2.10
(1.86–2.22)
1.99±0.21
1.89
(1.67–2.54)
HDL cholesterol,
mmol/dm3
0.92±0.10
0.92
(0.90–1.09)
0.99±0.08
1.03
(0.86–1.10)
0.94±0.12
0.92
(0.71–1.18)
1.04±0.07
1.09
(0.94–1.11)
0.99±0.15
1.09
(0.70–1.28)
Atherogenic
index
0.99±0.15
1.00
(0.79–1.18)
0.94±0.18
0.99
(0.62–1.36)
1.13±0.18
0.91
(0.75–1.59)
0.95±0.17
0.74
(0.68–1.01)
1.17±0.20
1.03
(0.73–1.42)
Total lipids,
g/dm3
2.02±0.24
2.04
(1.30–2.75)
2.15±0.16
2.14
(1.97–2.51)
1.99±0.23
2.10
(1.33–2.48)
2.28±0.24
2.18
(1.99–2.70)
2.07±0.17
2.22
(1.52–2.43)
Uric acid,
mmol/dm3
0.054±0.008
0.050
(0.033–0.072)
0.056±0.010
0.052
(0.041–0.078)
0.068±0.006
0.072
(0.057–0.081)
0.060±0.007
0.060
(0.051–0.070)
0.068±0.005
0.071
(0.061–0.077)
Aegopodium podagraria L. extract is
characterised by the high content of potassium
[10,12,40]. In certain cases this may lead to the
disadvantageous effect, for example, the rats receiving
excess fructose combined with hydrochlorothiazide
and a diet relatively low in sodium, an unfavourable
hyperaldosteronism with extensive renal excretion of
potassium and unfavourable shifts in glucose
metabolism [14]. Lipid exchange is also is known to be
exacerbated by aldosterone [43]. Evidently, in the
intact rat these effects were not manifested and all the
studied values of the lipid metabolism did not differ
significantly from the intact animals data.
Also there were no changes in uricemia. This
result is in good agreement with the data previously
obtained on mice in which uricemia remained
unchanged after a shorter course of administration [24]
(this study addressed mostly behavioral reactions and
uricemia was determined in the context of the possible
impact of purine metabolism changes on CNS [44] that
is poorly understood in relation to the herbal drugs
effects).
Uric acid renal excretion in rats after a similar
course, as reported in [19] showed a tendency to the
increase against the background of the both doses of
the extract, no changes were registered in the animals
receiving the tincture at a low dose (that is consistent
with our previous data [11]), while at a high dose the
tincture slightly decreased this value. Thus, under
physiological conditions, goutweed preparations do not
induce any shifts in purine metabolism, while in
pathological states they are able to induce a selective
normalising action.
The tincture causes restoration of uricemia,
decreased in alloxan-induced diabetic mice [13], while
in oxonate-induced hyperuricemic mice and rats the
tincture as well as the extract significantly reduce uric
acid blood level [10,11], the extract also exerts a
hypouricemic effect in rats receiving excess fructose
combined with hydrochlorothiazide. At the same time,
in other models of the metabolic disorders not causally
related to the purine metabolism, such as induced by
high doses of ethanol or dexamethasone, goutweed
preparations do not lead to the unwanted changes in
uric acid exchange (in dexamethasone-induced model
there is also favourable influence on the renal excretion
of this metabolite) [17,20].
Taking into account the possible
disadvantageous effects of hypouricemia [44,45], this
metabolic neutrality is a positive characteristic of the
preparations supposed to be used during long periods
(as drugs or as components of the functional foods).
Conclusions
1. The hypolipidemic effect of the extract and the
tincture obtained from the aerial part of goutweed
(Aegopodium podagraria L.) has been confirmed
under the conditions of alimentary lipemia. In the
test with olive oil loading, goutweed extract
(1 g/kg) significantly reduces the level of
triglycerides in blood plasma, goutweed tincture

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Харчова наука і технологія 17 Volume 11 Issue 4/ 2017
(1 cm3/kg) significantly decreases the level of
plasma total lipids.
2. In the intact rats after 12 days of administration
goutweed extract at doses of 100 mg/kg and
1 g/kg; goutweed tincture at doses of 1 and
5 cm3/kg do not influence on the values of the
lipid metabolism and do not induce any changes
in uricemia.
The metabolic neutrality of goutweed active
components, together with their influence on the lipid
metabolism values under the conditions of the
alimentary lipemia, substantiate the possibility of use
of this herbal raw material for functional foods
development.
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БИОЛОГИЧЕСКАЯ АКТИВНОСТЬ СНЫТИ ОБЫКНОВЕННОЙ
(Aegopodium podagraria L.) И ВОЗМОЖНОСТИ ЕЕ ПРИМЕНЕНИЯ
ДЛЯ КОРРЕКЦИИ НАРУШЕНИЙ ОБМЕНА ЛИПИДОВ
О.В. Товчига, к.фарм.н., доцент*/***, E-mail: farmacol@nuph.edu.ua
О.О. Койро, к.фарм.н. *, E-mail: farmacol@nuph.edu.ua
С.И. Степанова, к.фарм.н., доцент**, E-mail: bromatology@nuph.edu.ua
С.Ю. Штрыголь, д.мед.н., профессор*/***, E-mail: farmacol@nuph.edu.ua
В.В. Евлаш, д.техн.н., профессор****, E-mail: chem_mikro@hduht.edu.ua
В.Г. Горбань , к.техн.н., доцент****, E-mail: chem_mikro@hduht.edu.ua
Т.К. Юдкевич, н.с.***, E-mail: cndl@nuph.edu.ua
*кафедра фармакологии
**кафедра нутрициологии и фармацевтической броматологии
***Центральная научно-исследовательская лаборатория
Национальный фармацевтический университет, ул. Пушкинская, 53, г. Харьков, 61002
****кафедра химии, микробиологии и гигиены питания
Харьковский государственный университет питания и торговли, ул. Клочковская, 333, г. Харьков, 61051
Аннотация. В статье обобщены сведения о биологической активности перспективного растительного сырья:
надземной части сныти обыкновенной (Aegopodium podagraria L., Apiaceae). Освещена технология получения
препаратов из этого раститтельного сырья, охарактеризован их химический состав и фармакологические эффекты,
внимание акцентировано на возможностях коррекции нарушений обмена липидов и их профилактики. Приведены
экспериментальные данные, подтверждающие эффективность экстракта и настойки сныти обыкновенной в условиях
алиментарной липемии, наряду с их безопасностью у интактных животных. Так, гиполипидемическая активность
экстракта сныти (1 г/кг внутрижелудочно) и настойки сныти (1 см3/кг внутрижелудочно) была установлена на крысах
в тесте с нагрузкой оливковым маслом. У интактных крыс экстракт в дозах 100 мг/кг и 1 г/кг, а также настойка в дозах

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Харчова наука і технологія 19 Volume 11 Issue 4/ 2017
1 и 5 см3/кг не изменяют показатели обмена липидов после 12-дневного введения. Создание лекарственных препара-
препаратов, а также диетических добавок или функциональных пищевых продуктов на основе сырья сныти
обыкновенной является перспективным.
Ключевые слова: сныть обыкновенная (Aegopodium podagraria L.), растительное сырье, лекарственные
препараты растительного происхождения, обмен липидов, диетические добавки, функциональные пищевые продукты.
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Отримано в редакцію 19.09.2017 Received 19.09.2017
Прийнято до друку 22.10.2017 Approved 22.10.2017