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Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated perfused rat liver

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Different species from the Achillea millefolium aggregate are used against gastrointestinal and hepato-biliary disorders in traditional European medicine. In this work, a fraction enriched in dicaffeoylquinic acids (DCCAs) and luteolin-7-O-beta-D-glucuronide was investigated on its choleretic effect in the isolated perfused rat liver (IPRL) compared to cynarin (1,3-DCCA), the main choleretic compound of Cynara scolymus L. A fraction containing 3,4-, 3,5- and 4,5-DCCA and luteolin-7-O-beta-D-glucuronide was prepared by solid phase extraction from a 20% methanolic extract of yarrow. A total amount of 48.8% DCCAs and 3.4% luteolin-7-O-beta-D-glucuronide was determined by HPLC analysis with cynarin as internal standard. IPRL experiments revealed a dose-dependant increase in bile flow (23-44-47%) by the Achillea fraction. Choleresis was two- to three-fold higher than that of cynarin. The combined effect of DCCAs and luteolin-7-O-beta-D-glucuronide stimulated bile flow more effectively than the single compound cynarin. Due to their polar structure, these compounds are quantitatively extracted into teas and tinctures; hence, they seem to be the choleretic active principles in the traditional application forms of yarrow.
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Phytomedicine 13 (2006) 702–706
Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated
perfused rat liver
B. Benedek
a
, N. Geisz
a
,W.Ja
¨ger
b
, T. Thalhammer
c
, B. Kopp
a,
a
Department of Pharmacognosy, University of Vienna, PharmaCenter Vienna, Althanstraße 14, A-1090 Vienna, Austria
b
Department of Clinical Pharmacy and Diagnostics, University of Vienna, PharmaCenter Vienna, Althanstraße 14,
A-1090 Vienna, Austria
c
Department of Pathophysiology, Medical University of Vienna, Wa
¨hringer Gu
¨rtel 18-20, A-1090 Vienna, Austria
Abstract
Different species from the Achillea millefolium aggregate are used against gastrointestinal and hepato-biliary
disorders in traditional European medicine. In this work, a fraction enriched in dicaffeoylquinic acids (DCCAs) and
luteolin-7-O-b-D-glucuronide was investigated on its choleretic effect in the isolated perfused rat liver (IPRL)
compared to cynarin (1,3-DCCA), the main choleretic compound of Cynara scolymus L. A fraction containing 3,4-,
3,5- and 4,5-DCCA and luteolin-7-O-b-D-glucuronide was prepared by solid phase extraction from a 20% methanolic
extract of yarrow. A total amount of 48.8% DCCAs and 3.4% luteolin-7-O-b-D-glucuronide was determined by HPLC
analysis with cynarin as internal standard. IPRL experiments revealed a dose-dependant increase in bile flow
(23–44–47%) by the Achillea fraction. Choleresis was two- to three-fold higher than that of cynarin. The combined
effect of DCCAs and luteolin-7-O-b-D-glucuronide stimulated bile flow more effectively than the single compound
cynarin. Due to their polar structure, these compounds are quantitatively extracted into teas and tinctures; hence, they
seem to be the choleretic active principles in the traditional application forms of yarrow.
r2005 Elsevier GmbH. All rights reserved.
Keywords: Achillea millefolium s.l.; Dicaffeoylquinic acids; Choleresis; Isolated perfused rat liver
Introduction
Different species from the Achillea millefolium aggre-
gate are used in traditional European medicine as
infusions and tinctures against gastrointestinal and
hepato-biliary disorders due to their antiphlogistic,
spasmolytic and antimicrobial properties (Willuhn,
2002;Jurenitsch, 1992). While the antiphlogistic activity
is mediated by sesquiterpenes (Kastner et al., 1993;Sosa
et al., 2001), flavonoids are described as the antispas-
modic compounds (Lemmens-Gruber et al., 2005), and
the essential oil and sesquiterpenes exhibit antimicrobial
effects (Simic et al., 2002). However, the choleretic
principles of yarrow are still unknown.
Extracts from artichoke leaves are widely used in the
treatment of hepato-biliary dysfunction and digestive
complaints. Mono- and dicaffeoylquinic acids (DCCAs,
Fig. 1) and flavonoids as the main phenolic constituents
of Cynara scolymus L. are reported to have choleretic,
hepatoprotective and cholesterol-lowering effects (We-
gener and Fintelmann, 1999). A standardised artichoke
extract showed a considerable increase in bile secretion
in a randomised placebo-controlled double-blind study
(Kirchhoff et al., 1994). Furthermore, in the isolated
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0944-7113/$ - see front matter r2005 Elsevier GmbH. All rights reserved.
doi:10.1016/j.phymed.2005.10.005
Corresponding author. Tel.: +43 1 42 77 55 255;
fax: +43 1 42 77 95 52.
E-mail address: brigitte.kopp@univie.ac.at (B. Kopp).
perfused rat liver (IPRL) cynarin (1,3-DCCA) and other
DCCAs besides monocaffeoylquinic acids and flavo-
noids were reported to be the choleretic active principles
in artichoke leaves (Matuschowski, 1998).
As yarrow is traditionally applied similar to artichoke
and contains a considerable amount of DCCAs as well,
a fraction enriched in those phenolcarboxylic acids and
luteolin-7-O-b-D-glucuronide was prepared and tested in
the IPRL in order to examine its effect on bile flow. As a
positive control we used cynarin, the main choleretic
constituent of C. scolymus L. (Fig. 1).
Material and methods
Plant material
A commercial sample of the aerial parts of yarrow (A.
millefolium s.l.) supplied by Aboca, Sansepolcro, Italy
(sample 1D5787), was used for the preparation of the
plant extract. A voucher specimen (Aboca 1) is
deposited at the Department of Pharmacognosy, Uni-
versity of Vienna.
Preparation of the extract
Twenty-five grams of the powdered drug were
extracted with 1500 ml 20% (v/v) methanol p.a. for
30 min under reflux, followed by centrifugation. For
exhaustive extraction, the residue was treated in the
same way for another 20 min. Methanol was removed
from the combined extracts by evaporation under
reduced pressure at 40 1C. The remaining aqueous
solution was lyophilisated and yielded 9.1 g crude
extract, giving a drug–extract ratio of 2.7:1.
In order to obtain a fraction enriched in DCCAs, the
extract was dissolved in 270 ml 20% (v/v) methanol in
an ultrasonic bath for 10 min. Twenty millilitres of the
solution were applied to a C18-cartridge (Varian, Mega
BE-C18, 10 g, 60 ml), previously conditioned with 2
reservoir volumina (RV) methanol and 2 RV deionised
water. After purging with air for 10 min, the extract was
eluted at a flow rate of 8 ml/min with 4 RV deionised
water, followed by 4 RV 20% (v/v) methanol and 4 RV
80% (v/v) methanol, respectively. This procedure was
repeated several times in order to fractionate the whole
extract. From the combined 20% (v/v) methanol
fractions methanol was evaporated under reduced
pressure at 40 1C, and the remaining aqueous solution
was lyophilisated, affording 1.3 g of a fraction.
Analysis of the extract
To 4.2 mg of the fraction obtained by solid phase
extraction 200 ml of internal standard solution (1.04 mg
in 1 ml methanol) were added and diluted to 1.00 ml
with 20% (v/v) methanol. The solution was centrifuged,
and 10 ml were injected repeatedly onto the HPLC
column.
Analysis of the fraction was performed by HPLC on a
Perkin Elmer Series 200 instrument equipped with a
column oven and an UV/VIS detector set at a
wavelength of 345 nm. As stationary phase a 5mHypersil
BDS C18 (250 4 mm) column was used, the mobile
phase consisted of water adjusted to pH 2.8 with acetic
acid (A) and acetonitrile (HPLC-grade, Riedel-de Ha
¨en,
purchased from Sigma-Aldrich) containing 0.8% acetic
acid (B). Gradient elution was performed starting with
16% B at 0.1%/min for 20 min at a flow rate of 1.2 ml/
min and a temperature of 25 1C(Fig. 2).
Quantification of the DCCAs and the flavonoid
luteolin-7-O-b-D-glucuronide was carried out by internal
standardisation with cynarin (Sequoia Research Pro-
ducts, Oxford, UK; purity496%). As the DCCAs
contained in the sample are structural isomers of the
internal standard cynarin, we used a calibration factor
of 1 for all of them. As luteolin-7-O-b-D-glucuronide is
not commercially available, a calibration curve with the
internal standard cynarin and luteolin-7-O-b-D-gluco-
side (Extrasynthe
`se, Genay, France; purity498%)
instead of the glucuronide was established. We found
linear correlation from 0.059 to 0.297 mg/ml with a
correlation coefficient of 0.9993. The calibration factor
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OR1OR2
OR4
HOOC OR3
12
3
4
5
6
Quinic acid: R1 = R2 = R3 = R4 = H
O
OH
OH
OH
Caffeic acid (CA)
R1R2R3R4
Cynarin
3,4-DCCA
3,5-DCCA
4,5-DCCA CA
CA
CA
CA
CA
CACA
CA
HH
H
HH
HH
H
Fig. 1. Structures of dicaffeoylquinic acids from yarrow and
cynarin.
B. Benedek et al. / Phytomedicine 13 (2006) 702–706 703
was calculated, taking into account the molecular weight
of luteolin-7-O-b-D-glucoside and -glucuronide, as
0.877.
Liver perfusion
Male Sprague-Dawley rats (body weight: 180–270 g;
liver weight: 11.4–15.4 g) were purchased from the
Department of Animal Research and Genetics of the
Medical University of Vienna. Animals were housed in a
temperature- and humidity-controlled room under a
12 h light–dark cycle with free access to water and food.
Liver perfusion experiments were carried out as
described before (Ja
¨ger et al., 2003) on animals
anaesthetised with phenobarbital according to the
protocol approved by the committee of the institution.
Before the excision of the liver, glass canulas for the
influent perfusate were applied in the portal vein, for
the effluent perfusate in the vena cava inferior. For the
collection of bile, a canula was inserted into the bile
duct.
The excised liver was transferred to a chamber where
it was kept constantly at 37 1C. Perfusion was carried
out in a single pass system at a constant flow rate of
35 ml/min using freshly prepared Krebs Henseleit
bicarbonate–CO
2
buffer (KHB) pH 7.4 (118 mM NaCl,
4.5 mM KCl, 2.75 mM CaCl
2
, 1.19 mM KH
2
PO
4
,
1.18 mM MgSO
4
and 25 mM NaHCO
3
). The buffer
was equilibrated with 95% O
2
and 5% CO
2
during the
whole procedure. The perfusion pressure was constantly
monitored by measuring the water pressure. Single bile
drops falling from the bile duct canula were weighed
(approximately 8 mg) in order to determine the bile flow
by measuring the time interval between drops. The bile
flow rate is expressed in ml/g
liver
/min.
The basal flow was determined by equilibrium
perfusion with pure KHB for 30 min. Then 5, 10 and
20 mg of the Achillea fraction were diluted in KHB
giving final concentrations of 10, 20 and 40 mg/l. Livers
were perfused with those solutions for 10 min each,
followed by intervals of 10 min purging with pure KHB.
The increase in bile flow was expressed in percentage of
the basal value.
Cynarin was used as a positive control. A stock
solution of 120 mg in 6 ml ethanol was prepared and
added to the perfusion medium to give final concentra-
tions of 10, 20 and 40 mg/l. The perfusion procedure was
carried out under identical conditions as mentioned
above for the Achillea fraction.
Statistics
For statistical analysis, the arithmetic mean and
standard error of the mean (SEM) of three individual
experiments were calculated. Differences of po0.01
were regarded as statistically significant.
Results and discussion
As shown in Fig. 2, HPLC analysis of the fraction
prepared by eluting the Achillea extract with 20% (v/v)
methanol from C18-cartridges revealed a total amount
of 48.8% DCCAs (7.9% 3,4-DCCA, 24.2% 3,5-DCCA
and 16.7% 4,5-DCCA) and 3.4% luteolin-7-b-D-O-
glucuronide besides other minor compounds that could
not be identified because of their small amount in the
fraction. Due to its polar structure the flavonoid
luteolin-7-b-D-O-glucuronide eluted together with the
DCCAs. The remaining flavonoids, present in the crude
plant extract, were eluted with 80% (v/v) methanol from
the C18-cartridges, whereas chlorogenic acid, also a
major compound of the crude extract, was eluted with
water, thus not being present in the tested fraction.
As shown previously for the phenolic constituents
from artichoke (Matuschowski, 1998), the DCCAs are
the main choleretic active principles. In particular,
cynarin revealed an increase in bile flow of 20% at a
concentration of 5.7 mg and a perfusion rate of 1 ml/
g
liver
/min which corresponds to our results. Monocaf-
feoylquinic acids contribute to the choleretic activity to
a minor extent whereas the flavonoid luteolin-7-b-D-O-
glucoside exhibited no significant effect on bile flow
which explains that this study focussed on the DCCAs
from yarrow.
In the liver perfusion experiments both, the Achillea
fraction and cynarin, showed a dose-dependant increase
in bile flow in the tested concentration range. Fig. 3
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1
2
3
4
5
5 10 15 20
200
400
600
100
300
500
700
intensity (mAU)
time (min)
Fig. 2. HPLC analysis of a fraction enriched in dicaffeoylqui-
nic acids [3,4-DCCA (3), 3,5-DCCA (4), 4,5-DCCA (5)] and
luteolin-7-b-D-O-glucuronide (2) from a commercial Achillea
sample with cynarin (1) as internal standard on a 5mHypersil
BDS C18 (250 4 mm) column by gradient elution with
acetonitrile/H
2
O (pH 2.8) and detection at 345 nm.
B. Benedek et al. / Phytomedicine 13 (2006) 702–706704
shows the course of bile flow after 30 min equilibrium
perfusion with pure KHB followed by application of
increasing concentrations (10, 20, 40 mg/l; 10 min each)
of Achillea fraction with intervals of 10 min purging with
pure KHB. A dose-dependant increase in bile flow of
23.1% (76.9), 44.1% (717.2) and 47% (712.2) by the
Achillea fraction was observed. Compared to the single
compound cynarin, which was applied in the same
concentrations, showing an increase in bile flow of 5.1%
(72.0), 15.9% (73.6) and 21.6% (78.9), the Achillea
fraction exhibited a two- to three-fold higher increase
(po0.01) in bile flow (Fig. 4).
Candidates for the observed choleretic effect of the
Achillea fraction are the above-mentioned DCCAs,
amounting to 48.8% in the tested fraction, due to their
structural similarity to the choleretic active DCCAs
from C. scolymus L. Since they are not commercially
available and difficult to isolate, no experiments with the
pure compounds could be carried out. The DCCAs from
yarrow seem to act synergistically, thus stimulating bile
flow much more effective than the single compound
cynarin. The flavonoid luteolin-7-b-D-O-glucuronide
being also present in the fraction might also contribute
to the choleretic effect.
Due to their polar structure, mono- and DCCAs are
extracted almost quantitatively into infusions and
tinctures, the traditional application forms of yarrow
in traditional European medicine. While the results
obtained in this study indicate the choleretic effect of the
DCCAs, it is also known that chlorogenic acid exerts an
increase in bile flow (Matuschowski, 1998). Since all
those phenolcarbonic acids are present in yarrow with a
total amount of about 2.5%, we strongly believe that
they are the main choleretic active principles in yarrow,
thus justifying the traditional application in case of
hepato-biliary disorders.
Moreover, a randomised placebo-controlled double-
blind cross-over study revealed an increase in choleresis
up to 51.5% after oral intake of a standardised
artichoke extract containing 0.38% caffeoylquinic acid
derivatives, therefrom 0.16% DCCAs and 0.06%
cynarin which corresponds to a daily intake of 7 mg
caffeoylquinic acids in total and 1.1 mg cynarin,
respectively (Kirchhoff et al., 1994). In contrary, we
investigated a tea preparation from yarrow and found a
caffeoylquinic acid content of 10 mg per cup, therefrom
7.5 mg DCCAs. Considering the recommended dosage
of three cups of tea, a daily intake of 22.5 mg DCCAs is
reached, thus leading to the conclusion that tea
preparations from yarrow might exert a considerable
increase in bile flow.
Furthermore, we suggest a standardisation of phyto-
pharmaceuticals containing yarrow with regard to the
content of DCCAs, the compounds responsible for the
choleretic effect. As described above, we established a
HPLC method that allows a rapid analysis of the
DCCAs by internal standardisation with cynarin.
In conclusion, this is the first time an in vitro
choleretic effect of yarrow has been shown. Hence, a
choleretic activity can be considered also in humans
after oral intake of preparations containing yarrow due
to the phenolcarbonic acid content. Taking into account
the low risk of side effects and the further beneficial
therapeutical effects like spasmolytic and antiphlogistic
activity, yarrow preparations might be appropriate
especially for long-term treatment of digestive disorders.
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B. Benedek et al. / Phytomedicine 13 (2006) 702–706706
... In total, 12 of 28 identified compounds could be assigned to this substance class, with dicaffeoylquinic acids (19)(20)(21)(22)(23) being the most abundant phenolic acids. Based on the report of Benedek et al. (2006) [30], 3,4-, 3,5-and 4,5-di-O-caffeoylquinic acids may be among these compounds. These caffeic acid derivatives have already been proven for A. millefolium and are the main choleretic principles in these Achillea species [30]. ...
... In total, 12 of 28 identified compounds could be assigned to this substance class, with dicaffeoylquinic acids (19)(20)(21)(22)(23) being the most abundant phenolic acids. Based on the report of Benedek et al. (2006) [30], 3,4-, 3,5-and 4,5-di-O-caffeoylquinic acids may be among these compounds. These caffeic acid derivatives have already been proven for A. millefolium and are the main choleretic principles in these Achillea species [30]. ...
... Based on the report of Benedek et al. (2006) [30], 3,4-, 3,5-and 4,5-di-O-caffeoylquinic acids may be among these compounds. These caffeic acid derivatives have already been proven for A. millefolium and are the main choleretic principles in these Achillea species [30]. Moreover, they are involved in a wide range of plant stress responses and contribute to the protection of plants against high intensities of light and UV-B radiation. ...
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... It is extensively used in traditional medicines for the treatment of inflammation, pain and gastrointestinal disturbances (Miraldi et al., 2001;Sharma et al., 2004;Passalacqua et al., 2007). Previous researches revealed a diversity of pharmacological properties of A. millefoilum, such as anti-inflammatory (Benedek et al., 2007;Burk et al., 2010), analgesic (Pires et al., 2009), antitumor (Li et al., 2011, antioxidant (Wojdyło et al., 2007), cholagogue (Benedek et al., 2006), and antifungal (Falconieri et al., 2011) activities. Up to date, several types of compounds including sesquiterpenes, monoterpenes, flavonoids, and phenolic compounds have been reported from A. millefoilum (Ali et al., 2017;Si et al., 2006). ...
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Seven undescribed guaianolide sesquiterpene lactones, millefoliumins A−G, and five known analogues were isolated from the whole plant of Achillea millefolium L. growing in Xinjiang, China. Their structures were elucidated by analysis of spectroscopic data and comparison with literatures. The absolute configurations of millefoliumins A−G were determined by single-crystal X-ray crystallography, ECD data analysis along with quantum-chemical ECD calculations. The X-ray crystal structures of 8α-angeloxy-1β,2β,4β,5β-diepoxy-10β-hydroxy-6βH,7αH,11βH-12,6α-guaianolide and 8α-angeloxy-4α,10β-dihydroxy-2-oxo-6βH,7αH,11βH-1(5)-guaien-12,6α-olide were reported for the first time, and the full ¹³C NMR data of malaphyllidin were attributed for the first time. Millefoliumins F and G, and austricin could improve the melaogenesis by increasing the melanin content and tyrosinase activity of B16 melanoma cells. Millefoliumins A, C and D, and austricin showed anti-inflammatory activity against the NO production in LPS-induced RAW264.7 cells.
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The variability of the chemical composition of the aerial part of common yarrow (Achillea millefolium L.) was studied as a function of its environmental growth conditions. Samples of four populations of A. millefolium growing wild at various altitudes (1150, 1500, 1700, and 2450 m) above sea level were collected. Their essential oils were obtained by hydrodistillation followed by a determination of their chemical compositions by chromatography–mass-spectrometry. Analytical results showed that the yield of essential oil from the plants depended on the habitat and varied from 0.06 to 0.16 mL/100 g. The composition of the essential oil of A. millefolium comprised 61 constituents, of which 47 were identified, the main group being monoterpenes and their derivatives. The yield of essential oil and its composition were controlled by linear effects of several abiotic factors related to the altitude gradient.
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More than half of the population in developing nations depends on natural medication for treatment of different sicknesses and problems. Among them, Achillea millefolium from Asteraceae family is one restoratively significant plant called as “yarrow” and revealed as being utilized in folklore medication for sicknesses, for example, skin irritations, convulsive, hepatobiliary, and gastrointestinal issues. Monoterpenes are the most delegate metabolites, establishing 90% of the fundamental oils comparable to the sesquiterpenes, and a wide scope of chemical compounds have likewise been found. Distinctive pharmacological examinations in numerous in vitro and in vivo models have demonstrated the capability of A. millefolium with anti-inflammatory, antiulcer, anticancer activities, and so forth loaning help to the reasoning behind various of its conventional uses. Because of the essential pharmacological activities, A. millefolium will be a superior alternative for new medication discovery. Our chapter extensively gathers late phytochemical and pharmacological activities of A. millefolium, and should, accordingly, act as an appropriate reference for future investigation into the plant’s phytochemical profiling and by and large pharmacological assessment.Keywords Achillea millefolium PhytochemistryTherapeutic usesPharmacologyConstituents
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Capsella bursa-pastoris L. is widely found in countries such as Cyprus, Europe, Saudi Arabia, Turkey, Pakistan, India, Iraq, Iran, China, Azerbaijan, and in ethnomedical records of many other Asian countries. C. bursa-pastoris (L.) Medic—a traditional herb belongs to genus Capsella. Animal model-based preclinical studies have provided important comprehensive scientific data of its phytochemistry and phytopharmacology besides its various important uses. The main focus of this chapter aims to provide a detailed information about the traditional uses, scientific evidence-based pharmacological actions, and phytoconstituents from C. bursa-pastoris (L.) Medic based on the data available from the past 40 years. The data available shows that the plant’s crude extracts and some phytoconstituents have anti-inflammatory, smooth muscles contraction, infertility, antimicrobial, hepatoprotective, cardiovascular, anticancer, sedative, antioxidant, acetylcholinesterase inhibition potential. The data also showed that C. bursa-pastoris (L.) has a good nutritional value due to the presence of plethora of phytoconstituents which include flavonoids, phytosterols, phenolics, etc. Other than immense pharmacological potential, C. bursa-pastoris is a rich source of nutrients also. The available scientific data on ethnopharmacology, phytochemistry, and pharmacological actions of C. bursa-pastoris suggest that this plant can be a promising target for discovery and development of novel drugs for treating wide range of human ailments due to the safe and effective nature of C. bursa-pastoris. More scientific studies need to be carried out on this plant because different traditional uses and phytoconstituents.KeywordsEthnopharmacologyPhytochemistryPharmacological actionsPhytosterolsPhenolicsFlavonoidsAnti-inflammatory C. bursa-pastoris
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Cholelithiasis is most prevalent gastrointestinal diseases in Indian sub-continent because of consumption of Westernization diet, sedentary lifestyle and craving for fast food culture. This disease affects all peoples irrespective of gender and ages. However, the prevalence this disease is higher in the youngster age group up to 25 due to soft drink and tea consumption, low physical inactivity, high body mass index (BMI), frequent intake of junk food in the form of sweet foods and high refined sugars, low fibre contents, high fructose intake, fast food, high fat, and low vitamin C intake. Doctors follow surgical treatments such as laparoscopic cholecystectomy and open cholecystectomy, and non-surgical treatments such as endoscopy retrograde cholangiopancreatography (ERCP), oral dissolution therapy and shock wave lithotripsyto cure this gallstone disease. All these treatments are costly and have some post-operative complications. Hence, recent times most of the peoples seek alternative and traditional medication system such as Ayurveda, Yoga, Naturopathy, Unani, Siddha, Homeopathy and Acupuncture to treat various diseases without any side effects and at low cost. Among these, Siddha system of medicine is the foremost than all other medical systems in the world, in which the plants are used in various forms and through various root of delivery system to treat the diseases. Hence, in the present study, the plant Silybum marianum plant leaf extract and AuNPs of Silybum marianum are used to test the efficacy of gallstone prevention and dissolution in a cholesterol fed mice.
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The oil of a wild growing population of Achillea asplenifolia Vent, was studied for yield, composition and antibacterial activity. The major components in the oil were β-caryophyllene (17.6%), germacrene D (15.6%) and chamazulene (13.3%). In an antibacterial diffusion assay, the oil showed activity against all tested Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) and Gram-positive Staphylococcus aureus.
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The choleretic action of artichoke extract [main ingredient: cynarin (1.5-di-caffeoyl-D-quinc acid)] was investigated in a randomised placebo-controlled double-blind cross-over study (pilot study) [n = 20]. The effect of the standardized, artichoke extract: Hepar SL forte (administered as a single dose: 1.92 g, by the intraduodenal route in a solution of 50 ml of water) was studied by measuring intra-duodenal bile secretion using multi-channel probes. Thirty minutes after the test-substance was administered, a 127.3% increase in bile secretion was recorded, after 60 minutes, 151.5%, and after another 60 minutes, 94.3%, each in relation to the initial value. The relevant differences for the placebo were significant to the extent of p < 0.01 and were clinically relevant. The highest increase in the case of the placebo (139.5%) was seen after 30 minutes. At 120 and 150 minutes the volume of bile secreted under the active treatment was also significantly higher than under the placebo (p < 0.05). In the placebo group, bile secretion fell below the initial level after 3 hours. An effective period of about 120-150 minutes was regarded as satisfactory to influence enzymatic digestion and the motor function of the intestine when the test substance was given postprandially. No side effects nor changes in the laboratory parameters in connection with the experiment were observed. Results indicate that artichoke extract can be recommended for the treatment of dyspepsia, especially when the cause may be attributed to dyskinesia of the bile ducts or disorder in the assimilation of fat.
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Münster (Westfalen), Univ., Diss., 1998 (Nur beschränkt für den Austausch).
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The results of several clinical investigations showed the efficacy and safety of artichoke extracts (Cynara scolymus L.) in the treatment of hepato-biliary dysfunction and digestive complaints, such as sensation of fullness, loss of appetite, nausea and abdominal pain. Moreover earlier findings on a lipidlowering and hepatoprotective effect may be confirmed. In-vitro and in-vivo it has been possible to evaluate the underlying pharmacological mechanisms. Flavonoids and caffeoylquinic acids are mainly responsible for the observed actions.
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The topical anti-inflammatory activity of a germacrane derivative [1,4-dihydroxy-germacra-5E-10(14)-diene; DHGD] isolated from Achillea pannonica Scheele (Asteraceae) was investigated employing the Croton oil-induced dermatitis in the mouse ear. Its effects on the oedematous response and on leukocytes infiltration are described. The germacrane derivative significantly inhibited ear oedema in a dose-dependent manner, with an ID(50) of 0.40 micromol/cm(2). DHGD (0.75 micromol/cm(2)) provoked a global inhibition of the oedematous response (61 %) higher than that induced by an equimolar dose of indomethacin (43 %) within 24 hours; the reduction induced by hydrocortisone (0.10 micromol/cm(2)) was 68 %. The effect of DHGD (61 % inhibition) was higher than that of the equimolar dose of indomethacin (51 % inhibition) also on granulocytes recruitment at the site of inflammation. Hydrocortisone (0.10 micromol/cm(2)) reduced the cellular infiltrate by 44 %.
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Untersuchung der spasmolytischen Aktivität der Flavonoid-Fraktion aus Achillea millefolium s.l. am isolierten Meerschweinchendünndarm Die Flavonoid-Fraktion einer kommerziell erhältlichen Probe von Achillea millefolium s.l. sowie ihre Hauptflavonoide, Quercetin und zwei Flavonoid-Metabolite wurden am isolierten Meerschweinchendünndarm hinsichtlich ihrer spasmolytischen Wirkung getestet. Die Aglykone Quercetin, Luteolin und Apigenin erwiesen sich mit IC50-Werten von 7,8 µmol/L, 9,8 µmol/L und 12,5 µmol/L als am stärksten antispasmodisch wirksam. Rutin und die Flavonoid-Metabolite Homoprotocatechinsäure und Homovanillinsäure veränderten die Kontraktilität der isolierten terminalen Ilea nicht signifikant. Von den Ergebnissen kann abgeleitet werden, dass die Konzentration der im Schafgarbentee enthaltenen Flavonoide hoch genug ist, um zur spasmolytischen Wirkung im Magen-Darm-Trakt beizutragen. Die Wirkung ist hauptsächlich auf einen calciumantagonistischen Effekt und teilweise auf eine Mediator-vermittelte Reduktion der Kontraktilität zurückzuführen.
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Flavopiridol (FLAP) is a novel anticancer agent that is extensively glucuronidated in patients. Biliary excretion is the main elimination pathway of FLAP conjugates responsible for enterohepatic recirculation and for the main side effect diarrhea. To investigate the hepatic transport system for FLAP glucuronides, livers of Wistar and Mrp2-deficient TR- rats were perfused with FLAP (30 microM) in a single pass system. Biliary excretion and efflux into perfusate during a 60 min period greatly differ in TR- rats. While cumulative biliary excretion of M1 and M2 was significantly reduced to 4.3% and 5.4% efflux into perfusate was increased by 1.5 and 4.2-fold. This indicates that in control rats, M1 and M2 are almost exclusively eliminated into bile by Mrp2. Cumulative FLAP secretion into bile and perfusate, however, was non-significantly reduced by 36.7% and 43.2% in the mutant rat strain, suggesting that besides Mrp2, other transporters might also be involved in FLAP elimination. FLAP stimulates bile flow up to 24% in control rats, but secretion is nearly absent in TR- rats further supporting an efficient transport of FLAP glucuronides by Mrp2. FLAP (30 microM) also reversibly inhibited the Mrp2-mediated biliary elimination of bilirubin and bromsulphthalein in Wistar rats by 54% and 51%, respectively, indicating a competition with the elimination of Mrp2-specific substrates. In summary, we found that FLAP glucuronides are substrates of Mrp2 effectively inhibiting the biliary excretion of bilirubin. This may explain the increased serum bilirubin levels observed in cancer patients during FLAP therapy.
Beitrag zur Pharmakologie und Wirkstoff-Findung von Cynara scolymus L Mathematisch-Naturwissenschaftliche Fakulta¨ Fakulta¨estfaï Wilhelms-Universita¨ Universita¨ü nster Composition and antibacterial activity of Achillea asplenifolia essential oil
  • P Matuschowski
Matuschowski, P., 1998. Beitrag zur Pharmakologie und Wirkstoff-Findung von Cynara scolymus L. Ph.D. Thesis, Mathematisch-Naturwissenschaftliche Fakulta¨ Fakulta¨estfaï Wilhelms-Universita¨ Universita¨ü nster. Simic, N., Palic, R., Vajs, V., Milosavljevic, S., Djokovic, D., 2002. Composition and antibacterial activity of Achillea asplenifolia essential oil. J. Essent. Oil Res. 14, 76–78.
Investigation of the spasmolytic activity of the flavonoids in yarrow (Achillea millefolium s.l.) on isolated guinea-pig ilea. Fitoterapi, submitted for publication Beitrag zur Pharmakologie und Wirkstoff-Findung von Cynara scolymus L
  • R Lemmens-Gruber
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Lemmens-Gruber, R., Marchart, E., Rawnduzi, P., Engel, N., Benedek, B., Kopp, B., 2005. Investigation of the spasmolytic activity of the flavonoids in yarrow (Achillea millefolium s.l.) on isolated guinea-pig ilea. Fitoterapi, submitted for publication. Matuschowski, P., 1998. Beitrag zur Pharmakologie und Wirkstoff-Findung von Cynara scolymus L. Ph.D. Thesis, Mathematisch-Naturwissenschaftliche Fakulta¨tFakulta¨t, Westfa¨-Westfa¨lische Wilhelms-Universita¨tUniversita¨t Mü nster.