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Lady's mantle (Alchemilla vulgaris L., Rosaceae): A review of traditional uses, phytochemical profile, and biological properties

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  • Institute for Medicinal Plant Research "Dr. Josif Pancic"

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Lady's mantle (Alchemilla vulgaris L. syn. Alchemilla xanthochlora Rothm., Rosaceae) has been commonly used in folk medicine to heal inflammations in the mouth, bleeding of the nose, furuncules, gynaecological (menorrhagia and dysmenorrhoea), and gastrointestinal disorders. Although therapeutic indications for lady's mantle are non-specific diarrhoea and gastrointestinal complaints, it has been reported to exert, as well, a variety of biological activities, including wound healing, antimicrobial, neuroprotective, gastroprotective, cytotoxic, and antioxidant. Lady's mantle presents a valuable source of natural bioactive compounds, mostly phenolic compounds - a large amount of tannins, phenolcarboxylic acids, and flavonoids, being responsible for the abovementioned effects. In this work, a literature review of biological properties, investigated in in vitro and in vivo experiments in regard to the determined chemical profile is presented. In addition, the data reported are discussed, and the directions for further investigations are proposed.
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Review Article Natural Medicinal Materials vol. 40 (2020) 66
Lady’s mantle (Alchemilla vulgaris L., Rosaceae): A
review of traditional uses, phytochemical profile, and
biological properties
VANJA TADI ´
C1,*, NEMANJA KRGOVI ´
C1,AND ANA ŽUGI ´
C1
1Institute for Medicinal Plants Research "Dr. Josif Panˇ
ci´
c", Tadeuša Koš ´
cuška 1, 11000 Belgrade, Serbia
*Corresponding author:vtadic@mocbilja.rs
Received: November 11, 2020
Accepted: December 20, 2020
Published on-line: December 22, 2019
Published: December 25, 2020
Lady’s mantle (Alchemilla vulgaris L. syn. Alchemilla xanthochlora Rothm., Rosaceae) has been com-
monly used in folk medicine to heal inflammations in the mouth, bleeding of the nose, furuncules,
gynaecological (menorrhagia and dysmenorrhoea), and gastrointestinal disorders. Although thera-
peutic indications for lady’s mantle are non-specific diarrhoea and gastrointestinal complaints, it has
been reported to exert, as well, a variety of biological activities, including wound healing, antimicro-
bial, neuroprotective, gastroprotective, cytotoxic, and antioxidant. Lady’s mantle presents a valuable
source of natural bioactive compounds, mostly phenolic compounds a large amount of tannins, phe-
nolcarboxylic acids, and flavonoids, being responsible for the abovementioned effects. In this work,
a literature review of biological properties, investigated in in vitro and in vivo experiments in regard
to the determined chemical profile is presented. In addition, the data reported are discussed, and the
directions for further investigations are proposed.
Key words: Alchemilla vulgaris, lady’s mantle; phytochemical profile; traditional application; biological properties
http://dx.doi.org/10.5937/leksir2040066T
1. INTRODUCTION
In the last ten years, two revolutionary changes occurred in
classical medicine, which have great implications on the re-
search both in phytomedicine and natural products chemistry.
The first change can be described as a gradual withdrawal
from the dogma of mono-substance therapy and an increasing
transition to the treatment of patients with drug combina-
tions. We call this therapy multidrug therapy. The second can
be characterized as a transition to a new kind of multitarget
therapy, which is directed primarily toward the activation of
defense, protective, and repair mechanisms of the body rather
than toward the direct destruction of the damaging agents
(e.g. the tumor cell or the pathogenic microorganism). Phy-
tomedicine research has a good chance of contributing to these
new strategies through the development of new and better
drugs for evidence-based and rational therapy. Namely, phy-
totherapy has long followed and developed these strategies
by using mono-extracts or extract combinations containing
mixtures of bioactive compounds and by activating primar-
ily self-healing and protective processes of the human body,
rather than attacking and directly destroying the damaging
agents (Tadi´c et al.,2014).
Medicinal plants have been recognized as an inexhaustible
source of bioactive compounds which have been used since
ancient times for the treatment of many diseases. Herbal
medicinal products as potential therapeutic agents are be-
coming increasingly important in pharmacy and have great
popularity from the perspective of the general public who
perceive medicinal plants as a good alternative to the single
chemical entity medicines application. The benefit of using
herbal medicinal products for a particular illness is because
they contain a complex of active components with polyphar-
macological action and synergistic effects (Gibbons,2003). In
this contest, of great importance is to make a review of up to
date performed investigations on medicinal plants tradition-
ally used in the treatment of different health impairments.
One of these plants, that have medicinal quality to provide the
rational means for the treatment of many diseases, is Alchemilla
vulgaris L. syn. Alchemilla xanthochlora Rothm., commonly
known as lady’s mantle and bear’s foot, well-known species
from the genus Alchemilla (Rosaceae). The genus Alchemilla in-
cludes about 250 species growing on wet meadows in Europe,
western Asia, and North America (Evans and Evans,2009;
Duckstein et al.,2012). In Serbia, lady’s mantle is presented
with three subspecies (subsp. montana, subsp. pratensis and
subsp. vulgaris) (Vlaisavljevi´c et al.,2019). According to the
phytochemical studies, the aerial part of the plant contains
mostly phenolic compounds a large amount of tannins (el-
Review Article Natural Medicinal Materials vol. 40 (2020) 67
lagitannins, the main one is agrimoniin), phenolcarboxylic
acids (ellagic, gallic and caffeic acid) and flavonoids (quercetin
and kaempferol, and their glycosides) (Shilova et al.,2020).
ESCOP Monographs described lady’s mantle usage for non-
specific diarrhoea, gastrointestinal disorders, and dysmenor-
rhea based on human experience and long-standing use (Öz-
bilgin et al.,2019;Blumental et al.,1998;ESCOP,2003;Hager,
1979;Tucakov,1997). Lady’s mantle is traditionally used due
to its tannin content for the treatment of inflammation of the
upper digestive tract and diarrhoea internally, as a wound-
healing agent and astringent externally, and as gargle against
mouth and throat inflammation. In Bulgaria, it is used to heal
inflammations in the mouth, bleeding of the nose, furuncules,
and gynecological diseases, while in Poland is used as an anti-
inflammatory, carminative and anti-diarrheal remedy, and
against gastritis. It is also reported that the aerial parts of this
plant are used traditionally in Montenegro, internally to treat
mild and nonspecific diarrhoea, menopausal complaints, and
dysmenorrhea, and against ulcers, eczema, and skin rashes
externally (Ergene et al.,2010). Other Alchemilla species are
also used as a diuretic, in the treatment of liver inflammation,
asthma, bronchitis, cough, and diabetes, as well as kidney,
intestinal, and gastric disorders (Özbilgin et al.,2019). In this
paper, several most important biological effects of lady’s man-
tle extracts will be presented in relation to the determined
phytochemical profile.
2. PHYTOCHEMICAL ANALYSIS OF LADY’S MANTLE
Rational phytotherapy is a modern form of phytotherapy that
involves the treatment and prevention of diseases and health
impairments by applying herbal medicinal products based
on standardized extracts with clinically proven therapeutic
efficacy (Petrovi´c,2019). In standardized extracts, the active
constituents (single or groups) responsible for the assessed bi-
ological activities should be determined (Heinrich et al.,2012).
Hence, taking into account the principle of modern phytother-
apy, qualitative and quantitative analysis of plant extracts are
necessary to be performed. Due to the growing development
of new methods, the chemical analysis enabled the elucidation
of the molecular structure of secondary metabolites, at the
same time providing the identification or confirmation of the
structural identity of a chemical compound(s) responsible for
the evaluated biological activity. Generally, the presence of dif-
ferent types of polyphenol compounds in the plant materials
well correlates with numerous biological activities. Therefore,
according to the results presented in previous studies on the
chemical composition of various lady’s mantle extracts, the
major identified components which might be responsible for
the biological effects presented in this review were given in
Figure 1.
3. BIOLOGICAL EFFECTS OF LADY’S MANTLE
3.1. Wound healing
Human skin is permanently exposed to the external atmo-
sphere and is therefore easily prone to injury. However, it has
a natural ability to promote the self-regeneration after damage,
achieved through a complex biological process comprising
several overlapping biochemical and cellular phases. In this
context, investigations of the potential of medicinal plants to
accelerate wound healing may be especially applicable, due
to their multi-component nature hence providing several bio-
logical activities, such as antioxidant, anti-inflammatory, an-
timicrobial, and cell-stimulating properties, relevant to wound
healing management. The traditional usage of lady’s mantle in
wound healing has been confirmed in several recent scientific
studies (Choi et al.,2018;Tasi´c-Kostov et al.,2019).
In one of our previous papers, several extracts of lady’s mantle
aerial part were prepared by maceration with various solvents
(water, ethanol, and propylene glycol). Thereafter, stated ex-
tracts have been investigated for wound healing in the in vitro
scratch assay using L929 fibroblasts. With the idea of not
only the scientific justification of the traditional usage, but
also the correlation of wound healing activity to the chemical
composition of the investigated extracts, this study revealed
macerate prepared with ethanol to be the most abundant in
total phenolic, total flavonoid, and total tannins content and
at the same time to possess the strongest antioxidant activity
as well as the most pronounced effect of fibroblasts migra-
tion and the highest extent of wound closure. Hence, the
wound healing of lady’s mantle extracts was attributed to
phenolic compounds and their antioxidant activity. Further
assessed HPLC analysis (Figure 2) confirmed the presence of
different polyphenols (ferulic acid (1), rutin (2), hyperoside
(3), ellagic acid (4), isoquercetin (5), luteolin-7-O-glucoside
(6), kaempferol-3-O-glucoside (7), apigenin-7-O-glucoside (8),
luteolin (9), kaempferol (10), morin (11), quercetin (12) and
tiliroside (13)), with ellagic acid, isoquercetin and morin being
most abundant (the quantity varied from 1.9 to 6.5 mg/g dry
extract in the investigated samples). These three phenolic com-
pounds (ellagic acid, isoquercetin, and morin) were detected
in all investigated extracts, indicating their high content to
be partly responsible for the observed wound healing proper-
ties of the extracts (Tasi´c-Kostov et al.,2019). Indeed, a recent
study revealed ellagic acid (4) to be able to prevent collagen de-
struction and inflammatory responses caused by UV-B light, in
addition to previously reported prevention of cutaneous lipid
peroxidation, thus improving collagen production and subse-
quently increasing the speed of healing (Amadeu et al.,2003;
Bae et al.,2010;Jimenez et al.,2006;Singer and Clark,1999). In
this connection, Ili´c-Stojanovi´c et al. (2018) recently reported
the development of stimulus-sensitive hydrogels, which are
used as carriers for modified release of ellagic acid from lady’s
mantle extract. Aside from ellagic acid, another compound
found in lady’s mantle, quercetin-3-O-
β
-glucuronide (14) was
reported to stimulate collagen synthesis. Namely, the activity
of this compound as a collagenase inhibitor was higher than
doxycycline, a Federal Drug Administration (FDA)-approved
drug, used as a positive control in this study. It might be added
that aside from wound or burn healing, collagenase inhibitors
might be useful in the treatment of other skin-related diseases,
such as dermatitis, acne, urticarial, or photoaging (Mandrone
et al.,2018). Also, Vlaisavljevi´c et al. (2019) revealed amylase
and tyrosinase inhibitory effects of A. vulgaris, which might be
related to antidiabetic and skin-related diseases (Vlaisavljevi´c
et al.,2019). Improvement of wound healing of lady’s mantle
was also connected to its anti-inflammatory effects (Ghedira
et al.,2012), which were recently confirmed in the study of
Boroja et al. (2018) where a methanolic extract of aerial part
of this plant (in the concentration of 50
µ
g/mL) was shown to
inhibit the activity of COX-1 enzyme by 44.4 %, whereas the
inhibition of COX-2 was higher (63.6 %) (Boroja et al.,2018).
Aside from the papers dealing with the wound healing prop-
erties of the extracts of lady’s mantle, several papers dealt
with the stated activity of topical formulations containing ex-
tracts of this plant as active principles. For instance, Choi
et al. (2018) showed that the application of an ointment con-
taining the herbal mixture of lady’s mantle and Mimosa tenui-
flora (mimosa), another plant traditionally used to treat cu-
taneous wounds, on the dorsal skin wounds of mice led to
the faster healing process compared to conventionally used
ointment with fusidic acid, used as control. Further assessed
histological investigation revealed the mixture to promote re-
epithelialization, collagen synthesis, and regeneration of skin
appendages, while immunohistochemical analysis indicated
Review Article Natural Medicinal Materials vol. 40 (2020) 68
Fig. 1. Secondary metabolites identified in lady’s mantle (A. vulgaris L., Rosaceae) extracts investigated in the literature cited in the review
improvement of angiogenesis and stabilization of blood ves-
sels, as well as the acceleration of the formation of granulation
tissue. Also, the herbal mixture enhanced the migration of Ha-
CaT, fibroblasts, and HUVECs on a two-dimensional wound
model, and also promoted the proliferation of macrophages
and lymphatic vessels (Choi et al.,2018). Similarly, Tasi´c-
Kostov et al. (2019) investigated topical preparations (gels) con-
taining the extracts of lady’s mantle aerial parts as active prin-
ciples for wound healing using the in vitro scratch assay, com-
plemented by the in vivo test of barrier repairment of the skin
after skin damage induced using the detergent sodium lauryl
sulfate (SLS). Although there were no significant differences
between gels containing macerates of A. vulgaris aerial parts
prepared with various solvents (water, ethanol, and propylene
glycol) in the in vitro wound closure, the most prominent ef-
fect was observed in the case of the gel with propylene glycol
extract. Further assessed in vivo study revealed an increase
of transepidermal water loss (TEWL), as the measure of skin
barrier repairment, accompanied by the growth of stratum
corneum hydration after 7-day treatment with all investigated
Review Article Natural Medicinal Materials vol. 40 (2020) 69
Fig. 2.
Comparative HPLC hromatograms of propylene glycolic
(AP), ethanolic (AE) and water (AW) extracts of A. vulgaris (the
numbers asigned to peaks correspond to compounds presented in
Figure 1)
gels with lady’s mantle extracts. Such findings suggested hy-
drogels to be adequate vehicles for wound dressings on the
one hand, and indicated topical application of gels with lady’s
mantle extracts, regardless of the extraction solvent, to induce
the epithelial cell growth, thus promoting the wound healing
process, on the other (Tasi´c-Kostov et al.,2019).
In a similar experimental setup (in vivo investigation of the
effects on SLS-irritated skin), cream with the extract of lady’s
mantle in the concentration of 1.5 % was reported to provide
the best anti-inflammatory effect, among several creams with
the same action in different concentrations (1 %, 1.5 %, 2 %,
and 3 %). Namely, this concentration of the extract in a semi-
solid vehicle, after its seven-day application on artificially
irritated skin, led to the decrease of irritation i.e. recurrence of
erythema index (EI) to the level before irritation. In compar-
ison, cream with 1 % of the extract led to recurrence of EI to
initially accessed values (before irritation) only after nine days
of application. In addition, the increase of the extract concen-
tration from 1.5 % to 2 % or 3 % did not cause an increase in
the anti-inflammatory potential of the corresponding creams.
Chemical analysis of the lady’s mantle extracts incorporated
into the tested creams revealed the presence of tannins (not
less than 3.5 %), while further accessed HPLC analysis identi-
fied three major flavonoids to be isoquercetin (5), luteolin-7-O-
glucoside (6), and quercetin (12). Thereafter, the authors con-
nected the chemical composition of the extracts to the exerted
anti-inflammatory effect of the investigated creams. Namely,
quercetin and isoquercetin were previously shown to inhibit
both acute and chronic phases of inflammation, to possess
COX and lipoxygenase (LOX) inhibitory activities, and were
effective in the treatment of allergic reactions. In addition, they
are probably included in the inhibition of the production and
the release of histamine. On the other hand, biological effects
of tannins in animal and human cells and tissues are related
to their ability to chemically react with proteins and build
insoluble complexes, which is manifested in the precipitation
of proteins in the surface layers (astringent effect). In addition,
all identified compounds in the extract were shown to have a
pronounced antioxidant effect (Žižovi´c et al.,2016).
3.2. Antioxidant activity
Lately, a number of diseases such as Parkinson’s disease, can-
cer, cardiovascular, and obesity-related diseases have been
connected to oxidative stress, therefore underlining many sci-
entific reports investigations of antioxidative activity of differ-
ent compounds, and in particular the ones of plant origin. In
this connection, several authors reported strong antioxidant
activity of lady’s mantle (ESCOP,2003), but only the most
recent ones will be presented in this review.
In the investigation of (Boroja et al.,2018) different assays
were performed in order to compare the antioxidative po-
tential of the methanolic extracts of aerial parts and roots of
lady’s mantle. The results of this study pointed to significantly
better (P<0.05) antioxidant activity of the extracts prepared
from the aerial parts compared to the roots in all employed
methods, except for total antioxidant activity. Nevertheless,
the potential of the extract obtained from the aerial parts of the
plant to neutralize free radicals (DPPH
, ABTS
•+
, and
OH)
was significantly lower (P<0.05) compared to the synthetic
antioxidant butylated hydroxytoluene (BHT), while there was
no statistically significant difference compared to catechin. It
should be emphasized that particularly better antioxidant ac-
tivity in the inhibition of lipid peroxidation was observed for
this extract compared to the one prepared from the roots of
lady’s mantle. Such results were ascribed to the high amount
of polyphenols in the tested extract, where in the one obtained
from Alchemillae herba the major identified compound was
ellagic acid (Boroja et al.,2018).
Similarly, Vlaisavljevi´c et al. (2019) used several antioxidant
assays (DPPH, ABTS, CUPRAC, phosphomolybdenum, metal
chelating, FRAP) to compare the antioxidant potential of
methanolic, ethanolic, ethyl-acetate, and water extracts of
lady’s mantle. The authors found a strong correlation be-
tween total phenolic content and antioxidant activity, with
ethyl-acetate extract having the highest content of total phenol
compounds (9.65 mg GAE/g) and therefore the highest antiox-
idant activity. In general, the most pronounced and significant
antioxidant effects of tested extracts were observed for DPPH
and FRAP assays, where the best activity of the ethyl-acetate
extract was followed by methanolic and water extract, which
revealed significantly lower anti-radical activity compared to
the other extracts (Vlaisavljevi´c et al.,2019). Antioxidative
effects of macerates of Alchemillae herba prepared with wa-
ter, ethanol, and propylene glycol were recently confirmed in
DPPH and
β
-Carotene–linoleic acid assay. The activity of the
ethanolic extract was determined to be much higher than two
other extracts in DPPH test, which was in line with the highest
amount of total phenols, total flavonoids, and total tannins
in this extract; however, exerted antioxidant potential was
much weaker compared to the reference antioxidants (BHT
and BHA) (Choi et al.,2018;Tasi´c-Kostov et al.,2019).
3.3. Treatment of dysmenorrhoea
The application of the aerial parts of lady’s mantle in dysmen-
orrhea, which is recommended by its ESCOP monograph, is
in line with its traditional utilization against pruritus vulvae,
bleeding from the uterus, and menstrual pains (ESCOP,2003;
Vlaisavljevi´c et al.,2019).
Recently, a study by Vlaisavljevi´c et al. (2019) suggested that
the use of the plant in traditional medicine for woman re-
lated diseases might be scientifically justified due to hormone-
dependent anticancer activity (breast and ovarian anticancer
effects) observed for several lady’s mantle extracts. Namely,
in this study cytotoxic effects of methanolic, ethanolic, ethyl-
acetate, and water extracts of lady’s mantle from Southeast
Serbia (central Balkan) was investigated against several cancer
cell lines, including invasive cancer lines resistant to conven-
tional chemotherapeutics, such as human breast MCF7 and
ovarian A2780 cancer cells. The results of this study revealed
that ethyl-acetate extract generally had the strongest potential
to decrease tumor cells’ viability. Also, ovarian A2780 and
breast carcinoma MCF7 displayed a better response to treat-
ment with methanolic extract compared to the ethanolic one.
Different efficacy of used lady’s mantle extracts against tested
cell lines in this study might be connected to their different
chemical composition, especially when it comes to substances
with proven anticancer activity. For instance, caffeic (15) and
gallic acid (16), determined to be present only in the ethyl-
Review Article Natural Medicinal Materials vol. 40 (2020) 70
acetate extract, were previously shown to possess strong anti-
proliferative and cytotoxic properties in a wide range of tumor
types such as those used in this study. Stated effects of these
phenolic acids were achieved through several mechanisms
such as interference with main signaling pathways involved
in cell cycle progression and cell death, then interference with
migrative and invasive properties, epithelial/mesenchymal
transition, and angiogenesis, as well as the ability to sensitize
tumor cells to conventional therapeutics. Aside from these
components, genistein (17), protein tyrosine kinase inhibitor,
and quercetin (12), which were also present only in the ethyl-
acetate extract, were reported to display strong anticancer po-
tential through inhibition of cell cycle progression, induction
of apoptosis, affecting MAP-ERK signaling pathway, inhibit-
ing the metastatic properties of malignant cells (Vlaisavljevi´c
et al.,2019).
3.4. Neuroprotective activity
Various central nervous system (CNS) disorders including
neurodegenerative diseases, stroke, and trauma can be caused
by different biochemical reactions and substantial processes,
such as protein aggregation, reactions of free radicals, insuf-
ficient blood supply, glutamate excitotoxicity, and oxidative
stress, which lead to apoptotic or necrotic cell death. Medici-
nal plants are widely studied for their neuroprotection activity.
One of the biologically-active groups of secondary metabolites
in plants are polyphenols (flavonoids, phenolic acids, tannins)
which are powerful antioxidants with beneficial effects on
brain health. Polyphenols have been reported to exert their
neuroprotective actions through an ability to suppress neu-
roinflammation, to decrease oxidative stress, and to increase
the expression of genes that encode antioxidant enzymes, neu-
rotrophic factors, and cytoprotective protein (Lalkovicová and
Danielisová,2016).
Aging is the primary risk factor for most neurodegenerative
diseases, including Alzheimer’s and Parkinson’s disease. Few
or no effective treatments are available for these disorders,
which tend to progress in an irreversible manner and are as-
sociated with large socioeconomic and personal costs (Hou
et al.,2019). In Parkinson’s disease (PD) there is selective de-
generation of neuromelanin-containing neurons, especially
substantia nigra dopaminergic neurons, where the loss of
dopaminergic (DA) neurons therein leads to the typical motor
symptoms of the disease and constitutes the cardinal patho-
logic diagnostic criterion for PD. The dark-brown cytoplasmic
pigment neuromelanin (NM) accumulates with age and is the
main risk factor for PD. It is supposed that brain tyrosinase
overexpression implicates age-dependent neuromelanin pro-
duction in PD pathogenesis. Therefore, inhibitors of tyrosinase
may be a useful therapeutic option in the prevention of PD
(Carballo-Carbajal et al.,2019). Alzheimer’s disease (AD), the
most common dementia type, is a progressive, irreversible
neurodegenerative disease clinically characterized by cogni-
tive and behavioral impairments. The prevalence of AD is
rising and reaching epidemic proportions. It is stated that
decreased cortical acetylcholine levels in dementia patients
are in correlation with an increase in cognitive symptoms, and
available anti-dementia medications provide only modest and
transient cognitive benefits. Among them are cholinesterase
inhibitors (donepezil, rivastigmine, and galantamine), which
are indicated for the symptomatic management of mild to
moderately severe AD (Micov and Pecikoza,2020).
Recently performed studies gave evidence that some plants
worked as acetylcholinesterase inhibitors. Shilova et al. (2020)
performed an investigation of the neuroprotective properties
of the infusion of lady’s mantle aerial part in an experiment
on animals. They evaluated the effects of the infusion after
hypoxic exposure modeled by hypoxia in a hermetic chamber
on the number of free radicals reacting with the stable free
radical-chromogen DPPH, the content of LPO end-metabolite
thiobarbiturate-reactive products (TBA-RP), and orientational-
exploratory behavior indicators of animals. Infusion of the
aerial part of lady’s mantle (in dose 0.5 mL/kg) exhibited
neuroprotective properties, normalized the exploratory be-
havioral parameters of the animals after hypoxic exposure,
reduced the contents of TBA-RP by exhibiting antioxidant
properties and of antiradical antioxidants that increased as a
result of LPO activation in brain tissues due to oxidative stress
caused by hypoxic shock. Neuroprotective properties of lady’s
mantle infusion were probably due to phenolic constituents
(simple phenols arbutin (18), flavonoids rutin (2), hypero-
side (3), luteolin-7-O-glucoside (6), astragalin (7), apigenin-7-
O-glucoside (8), luteolin (9), kaempferol (10), quercetin (12),
apigenin (19), phenolcarboxylic acids - p-coumaric (20), sinapic
(21), ferulic (1), caffeic (15), gallic (16), chlorogenic (22) ellagic
(4), coumarins umbelliferone (23), esculetin (24), scopoletin
(25), esculin (26), primarily hydrolyzed tannins - ellagitannins,
the main one being agrimoniin (27), up to 10 %) (Shilova et al.,
2020).
The treatment of neurodegenerative disorders such as AD and
PD, include the use of acetylcholinesterase and tyrosinase in-
hibitors. While inhibitor of acetylcholinesterase was approved
in Europe for the treatment of AD (such as galantamine, iso-
quinoline alkaloid isolated from the Galanthus woronowii bulbs
(Bulduk et al.,2018), tyrosinase inhibition has become a pop-
ular target in drug development and research for PD. In a
line with this, three different concentrations (3 mg/mL, 1.5
mg/mL, and 0.75 mg/mL) of aqueous and 70 % ethanolic ex-
tracts of lady’s mantle and Filipendula ulmaria were evaluated
for their acetylcholinesterase and tyrosinase inhibitory effects.
The acetylcholinesterase inhibitory activity was determined
to be between 77.03 and 98.39 % (at the highest used dose,
being 3 mg/mL), and the tyrosinase inhibitory activity was
found to be between 60.00 and 90.65 % (at 3 mg/mL) for all
investigated plants extracts. The lady’s mantle 70 % ethanolic
extracts (3 mg/mL) showed higher acetylcholinesterase in-
hibitory activity compared to aqueous extract (96.50 84.86 %
). The result for galantamine, positive control, was 99.98 % (at
1.5 mg/mL). In addition, 70 % ethanolic extract of lady’s man-
tle (at 3 mg/mL) showed higher tyrosinase inhibitory activity
compared to aqueous extract (71.55 60.00 %). The result for
kojic acid, potent tyrosinase inhibitor was 94.2 % (at 3 mg/mL).
The evaluated activities might be assigned to the presence of
apigenin-7-O-
β
-glucoside, luteolin-7-O-
β
-glucoside, quercetin,
and rutin, whose enzyme inhibitory activities were confirmed
in earlier conducted research (Kim and Uyama,2005;Lee et al.,
2016;Si et al.,2012). Besides, it was suggested that these statis-
tically significant differences between extracts were due to the
higher content of polyphenols and proanthocyanidins (28) in
ethanolic extracts (Neagu et al.,2015).
3.5. Gastroprotective activity
Peptic ulcer disease represents the break in the inner lining of
the stomach, the first part of the small intestine, duodenum,
or sometimes the lower esophagus. The lifetime prevalence
of peptic ulcer disease in the general population has been
estimated to be about 5–10 %, and incidence 0.1–0.3 % per
year (Lanas and Chan,2017). The predominant symptom
of uncomplicated peptic ulcer is epigastric pain, which can
be accompanied by other dyspeptic symptoms such as full-
ness, bloating, early satiety, and nausea. The imbalance of
aggressive gastric luminal factors acid and pepsin and defen-
sive mucosal barrier function is the major mechanism in the
pathogenesis of peptic ulcer. Several factors such as smok-
ing, excessive alcohol use, drug use (especially nonsteroidal
anti-inflammatory drugs, NSAID), emotional stress, and psy-
Review Article Natural Medicinal Materials vol. 40 (2020) 71
chosocial factors contribute to ulcer formation by increasing
gastric acid secretion or weakening the mucosal barrier. More-
over, epidemiological studies revealed a very strong associa-
tion between Helicobacter pylori infection and duodenal and
gastric ulcers (Malfertheiner et al.,2009). Treatment of peptic
ulcers has been focused on mitigation of symptoms, healing
ulcers, and avoiding reappearance of the ulcer. For these
purposes several drugs are used, i.e. inhibitors of a proton
pump (omeprazole and lansoprazole), antagonists of the H2-
receptor (famotidine), and antibiotics. As an alternative treat-
ment method, herbal medicines present a source of different
biologically active substances (tannins, flavonoids, alkaloids,
triterpenoids, steroids, saponins, and coumarins) with antiul-
cerogenic activity, and their use is now considered integral to
practicing a healthy lifestyle (Asnaashari et al.,2018). H. py-
lori and the NSAIDs are the main aggressive factors involved
in the pathophysiology of gastroduodenal ulcer. Valcheva-
Kuzmanova et al. (2019) in their study aimed to investigate the
effects of four Aronia melanocarpa-based juices in a rat model
of indomethacin-induced gastric ulceration. The juices were:
AM1 and AM2 (produced from A. melanocarpa fruits at 20
°
C
and 60
°
C, respectively), AMRC (a mixture of AM2 with Rosae
caninae pseudofructus extract), and AMAV (A. melanocarpa juice
with Alchemillae herbae extract). The pre-treatment of rats with
the four juices ameliorated the severity of the ulcer model
which was demonstrated by macroscopic indices as well as by
histopathological and immunohistochemical investigations.
The ulcer number and ulcer area, as well as the ulcer score
and ulcer index, were reduced by pretreatment of rats with
juices. Juice AMAV, characterized by the highest total polyphe-
nol content, flavonoids, and phenolic acids, showed the best
gastroprotective effect. In this experiment, probably the most
important mechanism underlying the gastroprotective effect
of the juices was the inhibition of apoptosis. Juice AMAV an-
tagonized the effects of indomethacin on apoptosis markers
with the highest activity (Valcheva-Kuzmanova et al.,2019).
In another study, Krivoku´ca et al. (2015) revealed strong anti-
Helicobacter pylori activity of different extracts of Alchemilla
species, ascribing mainly the revealed effects to the presence
of ellagic acid in the investigated samples (Krivoku´ca et al.,
2015).
3.6. Protective role in cisplatin-induced toxicity
Cisplatin (cis-diamminedichloroplatinum-II) is a highly effec-
tive chemotherapeutic agent used in the treatment of testicular,
head and neck, ovarian, cervical, and non-small-cell lung can-
cers, whose clinical application is limited by side effects such
as nephrotoxicity, ototoxicity, and hepatotoxicity (Ojha et al.,
2016;Oun et al.,2018). Tissue injury caused by cisplatin can
be explained by oxidative damage, inflammatory processes,
and apoptosis (Abdel-Daim et al.,2019). Natural products and
phytochemicals can be used for the prevention of cisplatin-
induced toxicity. Based on the results of numerous studies
revealing strong antioxidant capacity in vitro, the possible ef-
fect of lady’s mantle methanol extracts obtained from aerial
parts and roots (AVA and AVR, respectively) was evaluated in
the prevention of cisplatin-induced hepatorenal and testicular
toxicity in rats. Results showed that application of cisplatin
decreased testosterone level and tissue’s antioxidants activ-
ity (SOD - superoxide dismutase, CAT - catalase, and GSH -
glutathione), while it increased levels of transaminases, ALP
(alkaline phosphatase), GGT (gamma-glutamyl transferase),
urea, uric acid, creatinine and TBARS (thiobarbituric acid reac-
tive substances). Treatments with AVA and AVR significantly
decreased the levels of serum parameters of the liver (total
bilirubin and ALP) and kidneys (urea and creatinine), and
improved enzyme antioxidant activity, while the impact of
extracts on other parameters was neutral or negative. Ellagic
acid, catechin (33) and catechin gallate (34) were dominant
components in both extracts (Juri´c et al.,2020).
3.7. Antibacterial and antifungal properties
Although there are over 200 types of antibiotics and
chemotherapeutics available on the world drug market today,
the problem of bacterial multidrug resistance remains. One
reason is the appearance and spreading of multiresistant and
pan-resistant agents around the world leading to severe infec-
tions in humans and animals. The World Health Organization
has declared the spreading of pan-resistant bacterial strains
"pandemic of pan resistance" because these strains were found
all over the world. Still, there is not one specific solution for
this phenomenon. Infections caused by pan-resistant agents
lead to death in more than 90 % of the cases. This is why the
scientists in the scientific literature call bacterial resistance to
antibiotics "the plague of the 21
st
century". In this context,
plants are considered as sources of non-antibiotic substances
with antibacterial activity, at the same time with no contri-
bution to further increase of the resistance. Another reason
for the utilization of plant extracts is their complex multi-
component nature that may be especially well suitable for
interfering simultaneously with multiple targets, encompass-
ing the possibility of low-dose administration of active agents
and therefore reducing the potential undesired events, while
at the same time providing prospective synergistic or additive
effects. The search for new and effective antimicrobial natural
products revealed that secondary metabolite isolated from
plant materials possessed the antimicrobial activity against
antibiotics resistant pathogens (Atef et al.,2019).
Morover, there is significant consumer demand for foods that
are minimally processed and free from synthetic chemical
preservatives with the perception of being "natural". As a
result, the food industry is facing great challenges to produce
naturally occurring food antimicrobials and antioxidants to
reduce the use of synthetic chemical preservatives and still
produce safe foods that are also regarded as healthy. The im-
pact of food-borne diseases on children, the aging population,
and the immunocompromised individuals, as an emerged
public health problem, caused the increased interest in the
utilization of plant extracts as antimicrobial agents for food
preservation. The World Health Organization has defined the
meaning of food-borne illness as the disease after ingestion of
contaminated food or water. Food contamination can occur
during any time between food production and consumption.
In addition, the epidemiology of foodborne diseases indicated
that the bacterial infections caused, mainly, by Salmonella enter-
itidis,Escherichia coli,Bacillus cereus, and Staphylococcus aureus
have become increasingly resistant to empirical antimicrobial
agents.
Recent studies performed by (Boroja et al.,2018) confirmed
significant antibacterial activity lady’s mantle aerial extracts.
Enterococcus faecalis,S. typhimurium,Micrococcus lysodeikticus,
and B. mycoides were the most sensitive examined bacterial
species to the tested lady’s mantle extracts, with MICs between
0.156 and 0.625 mg/mL revealing the moderate antimicrobial
activity. Namely, according to (Kuete,2010), an extract can be
considered as a potent antibacterial agent with significant an-
tibacterial activity with MICs below 0.1 mg/mL, while MICs
between 0.1 and 0.625 pointed to moderate activity against
bacterial growth. MICs above 0.625 mg/mL referred to weak
activity. On the contrary, Klebsiella pneumoniae was the most
resistant bacteria in the study (MIC = 5 and 10 mg/mL). MICs
values above 1 mg/mL for the investigated extracts were also
observed for Pseudomonas aeruginosa,B. subtilis,Azotobacter
chroococcum, and E. coli. As in the study ellagic acid and cat-
echin were used as reference compounds, catechin failed to
inhibit the growth of all tested bacteria at concentrations lower
Review Article Natural Medicinal Materials vol. 40 (2020) 72
than 0.5 mg/mL, while ellagic acid exhibited antibacterial po-
tential against the same bacteria as the extracts, but with MICs
being lower than those for the extracts for the majority of bac-
teria. The investigation of the antifungal activity against As-
pergillus brasiliensis,Phialophora fastigiate,Penicillium canescens,
Trichoderma viride,T. longibrachiatum,A. glaucus,Fusarium oxys-
porum,Alternaria alternata,Doratomyces stemonitis and yeast
Candida albicans revealed weak activity of the tested extracts
with MICs greater than 2.5 mg/mL (Boroja et al.,2018).
The antibacterial activity was evaluated as well, against food
poisoning bacteria including two strains of Gram-positive bac-
teria (B. cereus and S. aureus) and two strains of Gram-negative
bacteria (E. coli, and P. aeruginosa) using the disc diffusion
method and determining the minimal inhibitory concentra-
tion, revealing MIC values to be greater than 1 mg/mL. Gener-
ally, Gram negative bacteria such as E. coli,P. aeruginosa and S.
enteritidis were less sensitive to the antimicrobials because of
the lipopolysaccharide outer membrane of this group, which
restricts diffusion of phenolic compounds. In contrast, Gram-
positive bacteria (S. aureus,Listeria monocytogenes, or B. cereus)
are usually more susceptible to bioactive compounds of plants
due to the direct interaction of the cell membrane with their
lipophilic compounds (Seffo,2020).
3.8. Antiviral activity
Despite a global victory over smallpox, there is still a potential
danger of re-emergency of this infection, because zoonotic
orthopoxviruses pathogenic for humans (vaccinia, smallpox
buffalo, cowpox, and monkeypox) and their natural reser-
voir (various rodents) persist in many parts of Central Africa,
Eurasia, and South America. In spite that vaccination is the
most effective way of protection against smallpox and other
orthopoxviruses, vaccines can cause adverse side effects and
vaccine-induced complications. Besides, antiviral drugs, e.g.
Cidofovir and Glivec, have been shown to exhibit relatively
low activity against smallpox. In addition, constant mutations
that characterized the viral genome, contributed to overall
unsatisfactory outcomes of antiviral drug application, con-
currently developing the drug resistance to the virus. The
abovementioned problems necessitate the search for the devel-
opment of new antiviral drugs and new antiviral compounds
with different mechanisms of action. The unexpected side
effects of conventional drugs and the growing phenomenon
of resistance have led researchers to turn to the plant kingdom
as a source of potential new antiviral drugs. The plant com-
plexes have proved to be usually more active than their most
abundant isolated compounds because of existing synergistic
mechanisms. The interaction mechanisms of bioactive com-
pounds with target molecules were investigated on the cellular
and molecular level, but for detailed highlighting of the action
mechanism, the molecular docking studies were conducted,
as well (Denaro et al.,2020). Recently performed experiments
have shown that plants exhibited significant antiviral activity,
confirmed in in vitro and in vivo studies. However, the same
plants can have different antiviral activity against RNA or
DNA viruses, either enveloped or non-enveloped, and even
against different types or strains of a virus.
In the research performed by Filippova (2017), antiviral effects
of the aqueous solutions of the lady’s mantle aerial parts and
roots extracts were studied in vitro using a continuous cell
line of kidney cells of green monkey (Vero). Orthopoxviruses
vaccinia virus (VV, strain L IVP) and smallpox virus of mice
(ectromelia virus, EV, strain K-1) were expanded in Vero cell
culture. Antiviral activity of lady’s mantle extracts was evalu-
ated by changes in orthopoxvirus titers in Vero cell monolayer.
Increasing the concentration of all studied extracts of lady’s
mantle led to a decrease in the titers of VV and EV and, con-
sequently, to an increase in neutralization indices, calculated
as differences between Titer of control and Titer, experimen-
tally obtained for orthopoxviruses. In general, lady’s mantle
extracts suppressed the reproduction of orthopoxviruses (VV
and EV) in the culture of Vero cells. Further studies should be
aimed at the identification of the substance responsible for the
activity.
3.9. Other biological properties
Apart from the activities mentioned in subsections 3.1.– 3.8,
the detailed survey of the literature revealed that lady’s man-
tle extracts exerted other biological activities. The enzyme
inhibitory activities were confirmed. Namely, besides the
already described significant anti-cholinesterase and anti-
tyrosinase activities, lady’s mantle extracts exhibited the anti-
amylase activity. The presence of polyphenols such as catechin,
quercetin, and luteolin-7-O-
β
-glucoside in the investigated
extracts might be responsible for the shown activity (Jhong
et al.,2015;Martinez-Gonzalez et al.,2019;Vlaisavljevi´c et al.,
2019;Yilmazer-Musa et al.,2012). The study of Pawlaczyk
et al. (2009) has revealed the anticoagulant activity of lady’s
mantle which is traditionally used as an anti-inflammatory,
carminative and antidiarrheal remedy and also against gas-
tritis and burns in Poland. According to an in vivo study, the
extract prepared from the aerial part of lady’s mantle and
containing polyphenolic compounds was found to stimulate
synthesis and peripheral deiodination of thyroid hormones in
rats which were subjected to intense cooling. (Borodin et al.,
1999;Pawlaczyk et al.,2009). Lady’s mantle was reported to
possess inhibitory activity of pancreatic lipase, as well, shown
in the study of Slanc et al. (2009).
CONCLUSION
A detailed survey of the literature regarding chemical compo-
sition and biological properties of lady’s mantle (Alchemilla
vulgaris L., Rosaceae) confirmed its potential medicinal signifi-
cance. The recent scientific research confirmed some of lady’s
mantle biological properties recognized within traditional use,
such as effects on wound healing and dysmenorrhea. How-
ever, a lot of work remains to be done to determine optimal
treatments, doses, and formulae for the preparations obtained
from this plant. In addition, data about the interactions of
medicinal plants in the living system is scarce, opening the
direction of future research towards the pharmacokinetics and
pharmacodynamics investigation. Therefore, further investi-
gations should be performed to provide evidence of in vivo
biological effects as a prerequisite for their prospective clinical
confirmation.
ACKNOWLEDGMENTS
The authors wish to send their gratitude to Serbian Ministry of
Education, Science and Technological Development (Contract
No. 451-03-68/2020-14/200003).
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... На этом фоне возрастает популярность использования фитопрепаратов благодаря их уникальным свойствам, таким как низкая токсичность при достаточно высокой эффективности, широкий спектр терапевтического действия, комплексный органопротекторный эффект, гармонизирующее воздействие на все органы и системы организма, минимум побочных эффектов [5][6][7]. Фитотерапия нашла применение при первичной и вторичной профилактике различных заболеваний, а также как мера по оздоровлению и реабилитации широких слоев населения в условиях воздействия негативных факторов окружающей среды, в качестве средства, повышающего адаптационные резервы здорового организма, в спортивной медицине. На основании результатов современных исследований складывается представление о том, что разностороннее влияние компонентов растений на организм человека объясняется их информационно-регулирующей активностью. ...
... веществ, обладающих свойством нормализовать проницаемость капилляров [37]. Помимо флавоноидов, в траве и листьях МО находят фенолкарбоновые кислоты (галловую, эллаговую) и их производные [7,34,36], которые, представляя собой растительные вторичные полифенольные метаболиты, являются компонентами дубильных веществ [38]. ...
... Таким образом, изучая эффекты МО, исследователи имеют дело прежде всего с комплексом ПФС [39]. При этом конкретный количественный и качественный состав используемого продукта из МО зависит от пространственно-временных характеристик сырья (места произрастания, культивирования, инвазии насекомых, сезона сбора, стадии роста растений и т.п.), а также способа извлечения ПФС [7,9,11]. Поскольку наибольшая полнота лечебного эффекта растительных препаратов обусловлена естественным эволюционно выработанным комплексом компонентов растений, методики переработки последних для получения фитопрепаратов ориентированы на сохранение всего комплекса активных веществ растения, а не на выделение действующего вещества в очищенном виде. ...
Article
Adaptogens are a category of herbal medicinal products that enhance the adaptive reserves of the body, resistance to extreme factors and survival under stress. Adaptogenic properties have been revealed in dozens of plants, in particular, preparations based on raw materials from the Lady’s Mantle (Alchemilla vulgaris L.), a perennial herbaceous plant from the family Rosaceae, have a wide range of biological activity, including antioxidant, antiinflammatory, neuroprotective, anticancer and other, which allows them to be used for prevention and supportive therapy in the treatment of many pathological processes. The results of the authors’ own research and a number of literature data substantiate the presence of adaptogenic properties in this plant. The review analyzes the information in the scientific literature on the chemical composition of compounds included in preparations based on A. vulgaris raw materials, the modern interpretation of the concept of “adaptogen” and criteria for evaluating the adaptogenic properties of plants, and discusses possible molecular and cellular mechanisms that ensure the presence of such properties in the Lady’s Mantle.
... Phytomedicine research has recently proved a good contribution to the development of multitarget therapy directed principally for the stimulation of defense, protective and repair mechanisms of the body instead of confronting the damaging agents [1][2][3]. Cancer is one of the most common devastating diseases that has a good chance for the application of multitarget therapy using natural plant-based products [4,5]. Lady's mantle (Alchemilla vulgaris Auct. ...
... The cultures were incubated at 27 °C for two days, after which inhibition zones in mm were recorded for the control (A) and the treatments (B). The growth inhibition percentage was calculated according to Equation (1). The minimum inhibitory concentration (MIC) of the tested extract against the three bacterial strains was determined as the lowest extract concentration that suppresses the bacterial growth after 24 h of incubation: ...
Article
Despite the proven biological activity of the aerial part extract of Alchemilla vulgaris, scarce information is available about the activity of the root extract. This encouraged us to initiate the current investigation to study the cytotoxic activity of A. vulgaris methanolic root extract against various cancer cell lines in vitro, along with its antimicrobial activity and phytochemical screening. MTT assay was applied to test the cytotoxic effect against the prostate (PC-3), breast (MCF-7) and colo-rectal adenocarcinoma (Caco-2), together with normal Vero cells. Flow cytometry was employed to assess cell cycle arrest and apoptosis vs. necrosis in PC-3 cells. The expression of apoptosis-related genes (BAX, BCL2 and P53) was quantified by qRT-PCR analysis. The obtained results showed strong antiproliferative activity on the three cancer cell lines and the normal Vero cells in a dose-dependent manner. A high selectivity index (SI) was recorded against the three cell lines with PC-3 cells showing the highest SI and the lowest IC50. This effect was associated with cell cycle arrest at G1 phase and induction of total apoptosis at 27.18% being mainly early apoptosis. Apoptosis induction was related to the upregulation of the proapoptotic genes P53 and BAX and the downregulation of the antiapoptotic gene BCL2. Additionally, the extract demonstrated in vitro antibacterial activity against Agrobacterium tumefaciens, Serratia marcescens and Acinetobacter johnsoni. Additionally, it showed antifungal activity against Rhizoctonia solani, Penicillium italicum and Fusarium oxysporium. Seven phenolic acids and seven flavonoids were detected. The predominant phenolic acids were cinnamic and caffeic acids, while hisperdin and querestin were the principal flavonoids. These findings provide clear evidence about the promising proapoptotic effect of A. vulgaris root extract, which contributes to laying the basis for broader and in-depth future investigations.
... In addition, quercetin, one of the phytochemicals in AV, can decrease the risk of arteriosclerosis by inhibiting the oxidation of low-density lipoprotein, which reduces cardiac damage (Yücel and Yücel, 2020). Many compelling publications have endorsed the idea that AV supplementation boosts the effectiveness of antioxidant enzymes and mitigates the action of LPO (Jurić et al., 2020;Tadić et al., 2020). ...
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Introduction: Isoproterenol (ISO) is regarded as an adrenergic non-selective β agonist. It regulates myocardial contractility and may cause damage to cardiac tissues. Alchemilla vulgaris (AV) is an herbal plant that has garnered considerable attention due to its anti-inflammatory and antioxidant bioactive components. The present investigation assessed the cardioprotective potential of AV towards ISO-induced myocardial damage. Methods: Four groups of mice were utilized: control that received saline, an ISO group (85 mg/kg, S.C.), ISO + AV100, and ISO + AV200 groups (mice received 100 or 200 mg/kg AV orally along with ISO). Results and discussion: ISO induced notable cardiac damage demonstrated by clear histopathological disruption and alterations in biochemical parameters. Intriguingly, AV treatment mitigates ISO provoked oxidative stress elucidated by a substantial enhancement in superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione (GSH) content, as well as a considerable reduction in malondialdehyde (MDA) concentrations. In addition, notable downregulation of inflammatory biomarkers (IL-1β, TNF-α, and RAGE) and the NF-κB/p65 pathway was observed in ISO-exposed animals following AV treatment. Furthermore, the pro-apoptotic marker Bax was downregulated together with autophagy markers Beclin1 and LC3 with in ISO-exposed animals when treated with AV. Pre-treatment with AV significantly alleviated ISO-induced cardiac damage in a dose related manner, possibly due to their antioxidant and anti-inflammatory properties. Interestingly, when AV was given at higher doses, a remarkable restoration of ISO-induced cardiac injury was revealed.
... Among many plants that exert a variety of biological activities is Alchemilla vulgaris, widely known as lady's mantle, as many ethnomedicinal reports mention its well-known effects against disorders of the female reproductive system (pruritus vulvae, dysmenorrhea, heavy menstrual flow, menopausal complaints). In addition, its activity against reproductive system-related diseases (endometriosis, cysts, fibroids, and infertility) has been described [19][20][21][22][23]. The anticancer activity of this plant has been reported against tumors of the female reproductive organs (A2780 and HeLa), as well as against human prostate cancer (PC-3), human breast cancer (MCF-7), human melanoma A375, human lung carcinoma A549, and human colorectal cancer (Caco2, HCT116) cell lines in vitro [24][25][26]. ...
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Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.
... Extracts from Alchemilla vulgaris L. (Rosaceae) showed remarkable antioxidant and anti-inflammatory activities (17). Scientific data support its multiple biological effects (neuroprotective, gastroprotective, antimicrobial, cytotoxic, antioxidant) (18). The most important flavonoids in A. ...
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Research background The current changes in the global economy, characterised by the climate crisis and the economic and health impact of the COVID-19 pandemic, have led to a significant demand for medicinal herbs. This trend is expected to increase significantly by 2050. In this study, we investigated the biopotential of aqueous infusions of four medicinal plants: Calendula officinalis, Chelidonium majus, Teucrium chamaedrys and Alchemilla vulgaris. Experimental approach The flavonoid analysis of the aqueous infusions of the selected plants was carried out using the RP-HPLC technique. The antiproliferative activity of the prepared aqueous plant infusions was analysed against three human cancer cell lines (MDA-MD-231, T24 and A549), while the antioxidant potential was measured using three antioxidant methods (DPPH, FRAP and Rancimat assay). Results and conclusions T. chamaedrys had the highest total phenolics (expressed as GAE (2061±42) mg/L), free radical scavenging activity (IC50=1.9 mg/mL) and Fe(III) reducing antioxidant power (expressed as FeCl2 (9798±27) mg/L). At a concentration of 1 mg/mL, the antiproliferation of T24 by C. majus was 96 % and of MDA-MD-231 cells by A. vulgaris was 75 % after 72 h. After principal component analysis, T. chamaedrys and C. majus were grouped together. Quercetin glucoside and antioxidant capacity (DPPH) contributed the most to differentiate these infusions from the other two. Novelty and scientific contribution This study represents a comparative analysis of the biopotential of four medicinal plants. A new RP-HPLC method was developed to separate the flavonoids in the herbal infusions. This is the first report on the presence of kaempferol-3-O-rutinoside in C. officinalis and isorhamnetin-3-O-rutinoside in A. vulgaris aqueous infusion. For the first time, C. majus has been shown to contribute to the oxidative stability of edible oil. Furthermore, this is the first comparative study on the antiproliferative activity of selected medicinal plants against the cell lines MDA-MD-231, T24 and A549.
... SOD is the main component of enzymatic antioxidant defence mechanism that mitigates oxidative stress by catalysing dismutation of highly reactive O 2− into less reactive H 2 O 2 (Hoseinifar et al., 2020). The elevation of SOD activity observed up to 0.25 % dietary inclusion of extract (P < 0.05) in this study revealed an improved antioxidant status in the larvae, which may be correlated to the presence of phenolic compounds like tannins, phenol-carboxylic acids, and flavonoids (Fa Emeish et al., 2018;Tadic et al., 2020;Mansour et al., 2022) can also be linked to the FTIR result of our study. Previously it is reported that, T. arjuna bark is rich in large amount of phytosterol, lactones, flavonoids, phenolic compounds and tannins and glycosides (Mandal et al., 2013). ...
... The medicinal plant is mainly used by these populations to treat bacterial infections, fungal infections, anaemia, haemorrhages and diarrhoea [45,46]. Characterised by a high phenolic contents, the aerial part of species in the genus Alchemilla are traditionally used as sedative, anti-inflammatory agents, antioxidant agents, neuroprotective agents and hence against neurodegenerative disorders [47][48][49]. Early scientific studies with Alchemilla kiwuensis Engl. ...
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Alchemilla kiwuensis Engl. (Rosaceae) (A. kiwuensis) is an herbaceous plant traditionally used by Cameroonians to treat epilepsy and other central nervous system disorders. The present study evaluated the antiepileptogenic and antiepileptic effects of A. kiwuensis (40 mg/kg, 80 mg/kg) following Pentylenetetrazole (PTZ)-induced kindling as well as its sub-chronic toxicity. Following an initial i.p administration of a challenge dose (70 mg/kg), Wistar rats of both sexes received sub convulsive doses (35 mg/kg) of PTZ every other day, one hour after the oral gavage of animals with treatments, until two consecutive stage 4, in all animals of negative control. Seizure progression, latency, duration, and repetition were noted. Twenty-four hours later, animals were dissected to extract their hippocampi. The resulting homogenates were used to evaluate Malondialdehyde, reduced glutathione, catalase activity, GABA, GABA-Transaminase, glutamate, glutamate transporter 2, IL-1β and TGF-1 β. Sub-chronic toxicity was conducted according to OECD 407 guidelines. The lyophilisate of A. kiwuensis significantly increased the latency of seizure appearance, delayed seizure progression and decreased seizure repetition and duration. Biochemical analysis revealed that the lyophilisate significantly increased the catalase activity, reduced glutathione, GABA, glutamate transporter 2 and TGF-1B levels. The lyophilisate equally caused a significant decreased in the GABA-Transaminase activity, malondialdehyde, and IL-1 β levels. There was no noticeable sign of toxicity. A. kiwuensis possesses antiepileptic and antiepiletogenic effects by enhancing GABAergic neurotransmission and antioxidant properties, coupled to modulation of glutamatergic and neuroinflammatory pathways and is innocuous in a sub-chronic model. These justifies its local use for the treatment of epilepsy.
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Due to issues with the corrosion problem in the petroleum industry and the use of less ecologically acceptable corrosion inhibitors, great emphasis, within research on corrosion inhibitors, is now being put on green corrosion inhibitors (GCIs). In this study, Lady’s mantle flower extract (LMFE) has been observed as a plant-based GCI for carbon steel in a simulated CO2-saturated brine solution. The effectiveness of the inhibitor in static and flow conditions has been determined using potentiodynamic polarization with Tafel extrapolation and electrochemical impedance spectroscopy (EIS). In static conditions, the inhibitor has been tested at concentrations from 1 g/L to 5 g/L with an increment of 1 g/L per measurement, while, in dynamic (flow) conditions, the inhibitor has been tested at concentrations from 3 g/L to 6 g/L with an increment of 1 g/L per measurement. All measurements were performed at room temperature. EIS and potentiodynamic polarization methods showed that LMFE achieves maximum effectiveness in protecting carbon steel from corrosion when added at a concentration of 4 g/L in static conditions and at a concentration of 5 g/L in flow conditions. The test methods proved that the inhibitory effectiveness of LMFE is greater than 90% in both test conditions (static and flow). The inhibitor efficiency was attributed to the adsorption of LMFE on the carbon steel surface, which was demonstrated by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). A biodegradability of 0.96 and a toxicity of 19.34% for LMFE were determined. The conducted laboratory tests indicate that LMFE could be used as an effective corrosion inhibitor for CO2 carbon steel corrosion.
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Alchemilla vulgaris L., Trifolium pratense L. and Glycyrrhiza glabra L. are important remedies in traditional medicine, known for many usages, including treating gynecological diseases. Despite folkloric use of the plant materials, there is a lack of scientific data to support their therapeutic application. The aims of the present study were to evaluate the relative binding affinities (RBAs) of plant-derived phytoestrogens for estrogen receptor β (ERβ) using fluorescent biosensor in yeast and to apply this assay for the assessment of the potential of plant materials towards ERs and treatment of estrogen-related disorders. Ligand-binding domain of ERβ fused with yellow fluorescent protein (ERβ LBD-YFP) was expressed in S. cerevisiae and fluorescence was detected by fluorimetry and fluorescence microscopy. Structural basis for experimental results was explored by molecular docking. Yeast-based fluorescent assay was successfully optimized and applied for identification of natural phenolic compounds and phytoestrogen-rich plant extracts that interact with ERβ-LBD, making this biosensor a valuable tool for screening estrogenic potential of a variety of plant extracts. This assay can be used for preliminary testing of plant-derived or fungal extracts, but also other sources of environmental substances with ER-modulating activity in order to assess their possible effects on the female reproductive system.
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Ethnopharmacological relevance: The genus Alchemilla L. (lady's mantle) comprises 1000 species, of which more than 300 have been characterized from Europe. Notably, as folk medicines, Alchemilla species have long been prescribed for the treatment of dysmenorrhea, pruritus vulvae, menopausal complaints, and related diseases in women. This review summarizes the traditional uses, highlights promising plant species, and focuses on phytochemical and biological studies to highlight future areas of research. Aim of the review: This literature review aims to provide a comprehensive overview of Alchemilla species, covering their botany, traditional uses, phytochemistry, and biological and pharmacological activities, and to summarize the current research status to better understand the application value of Alchemilla plants in modern phytotherapy. Materials and methods: The search strategy utilized the major thematic platforms Reaxys, Web of Science, Google Scholar, Scopus, ScienceDirect, PubMed, the USDA Plant Database and Kew Science (Royal Botanic Gardens) and was performed with the term Alchemilla. These platforms were systematically searched for articles published from 1960 to 2023. Results and discussion: Alchemilla species, as members of the Rosaceae family, produce tannins, phenolic acids, flavonoids, anthocyanins, coumarins, triterpenes and violet compounds. Effort has been made with this comprehensive review of Alchemilla plants to highlight the recent developments and milestones achieved in modern phytochemistry and phytotherapy, underlaying a broad spectrum of the activities of these plants, such as antioxidant, anti-inflammatory, neuroprotective, antimicrobial, antiobesity, cardiovascular, anticancer, and wound healing effects. Conclusions: An increasing number of studies on the plants in the Alchemilla genus have provided data about the main constituents and their importance in modern medicine. Both in vitro and in vivo studies have indicated that Alchemilla plants possess an extensive spectrum of biological activities. Regardless of the remarkable medical potential of Alchemilla extracts, clinical studies are limited and need to be performed to produce safer and less expensive plant-based drugs.
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Acetone/water extracts from the leaves, including stalks, of Alchemilla vulgaris L. and A. mollis (Buser) Rothm. were investigated for their phenolic composition by liquid chromatography- tandem mass spectrometry (LC-MS/MS). A total of 24 and 27 compounds were detected for A. vulgaris and A. mollis, respectively. Pedunculagin and agrimoniin, as described in earlier reports for A. vulgaris, as well as other monomeric and oligomeric ellagitannins such as sanguiin H-10, castalagin/vescalagin, and galloyl-bis-hexahydroxydiphenoyl (HHDP) hexose constituted the major phenolic fraction of both plant species. Also, gallic and chlorogenic acids were found in both extracts. Interestingly, catechin and a procyanidin trimer were detected only in A. mollis. The fl avonoid fraction comprised quercetin glucuronide as major compound in addition to several other quercetin glycosides. Most interestingly, a tentatively identifi ed kaempferol glucuronide and a methylated quercetin glucuronide were exclusively found in A. mollis. Finally, the overall phenolic fingerprints of both Alchemilla species, harvested in May and August, i.e. at the beginning and the end of the flowering period, were compared. A general accumulation of phenolic constituents was observed later in the year, especially with regard to the ellagitannins.
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Alzheimer’s disease (AD), the most common cause of dementia, is growing health, social and economic issue because of the increasing number of sufferers, limited efficacy of available treatment options, and high total healthcare costs. It is clinically characterized by cognitive and behavioral impairments, both of which need to be treated appropriately to improve patients’ quality of life and their caregivers as well. Currently, available anti-dementia medications provide only modest and transient cognitive benefits. Donepezil, rivastigmine and galantamine (cholinesterase inhibitors) are indicated for the symptomatic management of mild to moderately severe AD, while memantine (NMDA glutamate receptors antagonist) is recommended for moderate-to-severe AD. A special focus on behavioral symptoms (e.g. anxiety, depression, aggression) management is required as they cause great suffering in patients/caregivers. The use of medications that can impair cognitive function, such as drugs with anticholinergic activity, should be avoided in patients with dementia. Additionally, interventions that could delay or prevent dementia onset in some subjects are focused on minimizing modifiable risk factors (hypertension, diabetes, depression) and maximizing protective factors (physical activity, healthy diet, leisure, and social activities). The treatment of AD remains a challenge. Key words: Alzheimer’s disease, donepezil, rivastigmine, galantamine, memantine, pharmacist-led interventions
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The infusion from the aerial part of common lady’s mantle Alchemilla vulgaris L. injected preliminarily for 5 d exhibited neuroprotective properties by normalizing conditioned reflexes and orientational-exploratory behavior indicators of animals after hypoxic exposure. Infusion at a dose of 5 mL/kg was the most active. A. vulgaris infusion at a dose of 5 mL/kg with activation of lipid peroxidation after hypoxic action normalized the content of thiobarbiturate-reactive products in brain homogenate and reduced the concentration of antiradical antioxidants in the lipid extract.
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The current study was designed to evaluate the phytochemical profile and biological properties (antioxidant, enzyme inhibitory and cytotoxic activity) of methanolic, ethanolic, ethyl-acetate and water extracts of Alchemilla vulgaris from Southeast Serbia (central Balkan) which was traditionally used to alleviate and treat many diseases. Bioactive compounds were characterized by LC-MS/MS technique and biological properties were evaluated using antioxidant, enzyme inhibitory and cytotoxic assays. Twenty-six phenolic compounds were quantified in methanolic, ethanolic, ethyl acetate and water extracts, whereas the highest yields were found in ethyl-acetate (EA) extract (gallic acid, caffeic acid, catchin, quercetin). This extract has also shown the greatest antioxidant, anticancer and inhibitory enzyme activities which were demonstrated for the first time in this study. The obtained results indicated that Alchemilla vulgaris from South Serbia possesses high potential for pharmaceutical applications.
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According to legislation of EU, as well as of our country, herbal medicinal products (HMPs) and traditional herbal medicinal products (THMPs) are categories of medicinal products. As active ingredients, they contain herbal drugs (herbal substances) and/or herbal drug preparations (herbal preparations). HMPs are authorized based on proved quality, clinical efficacy and safety. THMPs are registered based on proved quality and sufficient data on traditional use (acceptable safety level and plausible efficacy). The Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency (EMA) publishes EU herbal monographs, which comprise preclinical and clinical data on HMPs with well-established use (WEU), as well as data on traditional use (TU) for THMPs. HMPC also develops drafts of EU list entries for THMPs, which are adopted and their final versions are published by the European Commission. By the end of July 2019, HMPC issued 160 final monographs, which are available on the EMA website (157 monographs for 156 herbal drugs and herbal drug preparations, two monographs for two herbal drug combinations, and monograph for herbal tea combinations); EU list entries on 13 herbal drugs and preparations were finalized. This paper provides an overview of the therapeutic areas and indications approved in these final EU monographs. In addition, overview of HMPs and THMPs, which are authorized/registered in the Republic of Serbia is given.
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Ageing is the primary risk factor for most neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD). One in ten individuals aged ≥65 years has AD and its prevalence continues to increase with increasing age. Few or no effective treatments are available for ageing-related neurodegenerative diseases, which tend to progress in an irreversible manner and are associated with large socioeconomic and personal costs. This Review discusses the pathogenesis of AD, PD and other neurodegenerative diseases, and describes their associations with the nine biological hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion and altered intercellular communication. The central biological mechanisms of ageing and their potential as targets of novel therapies for neurodegenerative diseases are also discussed, with potential therapies including NAD+ precursors, mitophagy inducers and inhibitors of cellular senescence.
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Due to rapid development of microbial resistance against chemotherapeutic agents (mostly antibiotics), it has become essential currently to screen effective, safe, cheap, and available therapeutics from various medicinal plants—like herbs—for their potential antimicrobial effect. To estimate the antibacterial activity of aqueous, ethanol, and methanol extracts of each of Moringa oleifera L. leaves and Matricaria recutita L. flowers against antibiotic-resistant and sensitive bacterial strains isolated from patients having wound infections. In the present study, a total of one hundred clinical samples were obtained from different cases of infected wounds. Forty isolates (40%) of pure bacterial cultures were detected. Pseudomonas aeruginosa was found to be the predominant agent isolated from the wound infections (32.5%) followed by Staphylococcus spp. (25%), E. coli (20%), Klebsiella spp. (20%), and Proteus mirabilis (2.5%). Sensitivity of the bacterial isolates was tested against antibiotic discs: piperacillin, ampicillin, oxacillin, pinicillin, gentamicin, tobramycin, amikacin, streptomycin, ceftriaxone , ceftazidime, cefoxitin, cefoperazone, cefuroxime, cefepime, cefotaxime, ciprofloxacin, oflaxacin, levofloxacin, lomefloxacin, moxifloxacin, tetracycline, aztreonam, azithromycin, erythromycin, imipenem, piperacillin-tazobactum, ampicillin-sulbactam, linezolid, teicoplanin, trimethoprim-sulphamethoxazole , chloramphenicol, and clindamycin. Out of the 40 bacterial strains studied, 20 isolates were multidrug-resistant (MDR), 7 extensively drug-resistant (XDR) and 3 were pan drug-resistant (PDR). The in vitro susceptibility test showed that the water, ethanol (95%), and methanol (80%) extracts of Moringa oleifera L.(leaves) and Matricaria recutita L.(flowers) produced an inhibitory effect against 12 resistant MDR, XDR, and PDR test isolates, with minimum inhibitory concentration (MIC) ranging from 7.8–62.5 mg/ml. Water and methanol extracts of both plants represented good activity against most of the sensitive and resistant isolates whereas ethanol extract of both plants showed a lesser activity against nearly all of the isolates This study had the potential value to develop antibacterial agents against resistant (MDR, XDR, and PDR) and susceptible bacteria supporting the significant use of plant extracts in treating wound infections related to bacteria and these active extracts will provide useful information for discovering new compounds with better activity and more effective against resistant (MDR, XDR, and PDR) and susceptible bacteria responsible for wound infections than currently available antibiotic agents.
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Viral infections represent one of the main causes of disease worldwide, especially today due to the increase of migration, global travel, and urbanization. The several side effects of the conventional drugs and the growing phenomenon of resistance have led researchers to turn to the plant kingdom as a source of potential new antiviral drugs. The aim of this work is to summarize the updated evidence for antiviral activity of different plants and their isolated bioactive compounds, evaluating also the potential interactions, which can occur in cotreatment with conventional antiviral drugs. The plant complexes have proved to be usually more active than their most abundant isolated compounds by hypothesizing synergistic mechanisms. In addition to cellular and molecular investigations, molecular docking studies have proved essential in highlighting the interaction mechanisms of bioactive compounds with target molecules. However, the use of nonstandardized extracts, or too high concentrations in vitro, which do not reproduce their bioavailability in vivo, are often limiting factors. Moreover, the lack of studies concerning the safety profile of plant extracts and their isolated compounds, alone or in combination with conventional antiviral drugs, is the most worrying aspect. In light of this, further studies are needed to validate their possible therapeutic use.
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This study was designed to evaluate the possible effect of methanol extracts of aerial parts and roots of Alchemilla vulgaris L. (AVA and AVR, respectively) in preventing cisplatin-induced hepatorenal and testicular toxicity in rats. UHPLC/DAD/(−)HESI-MS/MS analysis was performed to determine the detailed phenolic profile of AVA and AVR. The male Wistar rats were orally treated with extracts at three different concentrations (50, 100, and 200 mg/kg b.w.) for 10 days and toxicity was induced by injection of single dose of cisplatin on the 5th day (7.5 mg/kg b.w.). Determination of serum biochemical markers of hepatorenal and testicular tissue injury, as well as oxidative-stress parameters in tissues and histopathological study, were performed. Treatments with AVA and AVR significantly attenuated the levels of serum parameters of liver, kidneys and testicles injury, tissue's morphology and parameters of oxidative stress caused by an application of the cisplatin. Chromatographic analysis showed the presence of more than 20 different phenolic compounds in extracts where ellagic acid, catechin, and catechin gallate were dominant components in both extracts. The obtained results indicate that A. vulgaris extracts may be used in preventing cisplatin-induced toxicity during chemotherapy as well as in the treatment of oxidative stress-related disorders.
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The aim of the study was to investigate the effects of four Aronia melanocarpa-based juices in a rat model of indomethacin-induced gastric ulceration. THE JUICES WERE: AM1 and AM2 (produced from aronia fruits at 20 °C and 60 °C, respectively), AMRC (a mixture of AM2 with Rosa canina extract) and AMAV (aronia juice with Alchemilla vulgaris). Male Wistar rats were used. Each of the juices (10 ml/kg) was administered for 10 days. Indomethacin (30 mg/kg) was injected subcutaneously and after 4 h, the effects were estimated. Indomethacin caused heavy destructions of the gastric mucosa, increased the expression of Bax and decreased the expression of Bcl-2, induced a certain increase in lipid peroxidation and a slight decrease in gastric PGE2 content. The pretreatment with the juices reduced the severity of indomethacin-induced gastric lesions and antagonized the effects of indomethacin on apoptosis and lipid peroxidation. The highest was the protective effect of AMAV, the juice with the highest polyphenolic content. The protective effect of Aronia melanocarpa-based juices against indomethacin-induced gastric lesions could be attributed to their polyphenolic contents. The mechanism involved to the highest extent in the protective effect of the juices was the inhibition of apoptosis.