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Leonurus cardiaca L. as a Source of Bioactive Compounds: An Update of the European Medicines Agency Assessment Report (2010)


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Leonurus cardiaca L. (motherwort) is a perennial herb, native to Asia and southeastern Europe, with widespread global occurrence in present days. The plant was historically used as cardiotonic and for treating gynaecological afflictions (such as amenorrhea, dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on Leonurus cardiaca L., herba (2010). The current study presents the progress made within the 2010-2018 timeframe regarding the potential applications and scientific evidences supporting the traditional use of motherwort, in the same time suggesting future research opportunities.
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Review Article
Leonurus cardiaca L. as a Source of Bioactive Compounds:
An Update of the European Medicines Agency Assessment
Report (2010)
Radu Claudiu Fierascu,1,2 Irina Fierascu ,1,2 Alina Ortan,1
Ioana Catalina Fierascu,3Valentina Anuta,3Bruno Stefan Velescu,3
Silviu Mirel Pituru,3and Cristina Elena Dinu-Pirvu1,3
1University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 M˘
,ti Blvd., 011464, Bucharest, Romania
2National Institute for Research & Development in Chemistry and Petrochemistry – ICECHIM Bucharest, 202 Spl. Independentei,
060021, Bucharest, Romania
3University of Medicine and Pharmacy “Carol Davila”, 37 Dionisie Lupu Str., 030167, Bucharest, Romania
Correspondence should be addressed to Irina Fierascu;
Received 25 February 2019; Revised 22 March 2019; Accepted 31 March 2019; Published 17 April 2019
Academic Editor: Francesca Mancianti
Copyright ©  Radu Claudiu Fierascu et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Leonurus cardiaca L. (motherwort) is a perennial herb, nativeto Asia and southeastern Europe, with widespread global occurrence
in present days. e plant was historically used as cardiotonic and for treating gynaecological aictions (such as amenorrhea,
dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively
well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on
Leonurus cardiaca L., herba (). e current study presents the progress made within the - timeframe regarding the
potential applications and scientic evidences supporting the traditional use of motherwort, in the same time suggesting future
research opportunities.
1. Introduction
Leonurus cardiaca L. (common names – motherwort in Eng-
lish, Echte Herzgespann –Deutsch,agripaume –French,
etc) represents a perennial herb belonging to the Lamiaceae
family. e plants grow up to  m, with the hollow aerial
stalks growing from the rhizomes. e leaves are palmately
lobed, being covered with sti hairs. Flowers, grouped in
- clusters in the leaf ’s axils of the last - knots, are
pink and about  cm long []. e plant, original to Asia
and southeastern Europe is now world-spread, due to its
medicinal use [–]. e potential application in treating
several cardiac disorders, as well as female-specic aictions,
made L. cardiaca a very good candidate for development
of alternative treatments, in both traditional eastern and
modern medicine [, ]. Besides the traditional medical use,
motherwort is used in some cuisines as condiment in various
vegetable soup recipes, particularly the lentil or split peas
ones, or for avoring of beer and tea [], thus increasing the
potential intake of the medicinal plant by the general public.
e current review intends to present the main ndings
regarding the composition and main biological activities of
L. cardiaca, as emerging from the scientic studies pub-
lished within the - timeframe. e time period
was selected in order to complete the very comprehensive
Assessment report on Leonurus cardiaca L., herba” pub-
lished by the European Medicine Agency [] with the latest
ndings. e search methodology involved accessing and
evaluating the papers found in the PubMed, ScienceDirect,
Wiley Online Library, ACS Publications, and SpringerLink
databases (search term “Leonurus cardiaca”, ..). Aer
the removal of duplicate entries,  studies were taken
into consideration. Figure  describes the distribution of the
reviewed works by publication year and type of paper. Most of
the information presented in the present work was collected
from the “Article” type papers ( works).
BioMed Research International
Volume 2019, Article ID 4303215, 13 pages
BioMed Research International
2011 2012 2013 2014
Publication year
Reviewed works
Book chapters
Others (Review, Editorial, Meeting Abstract, Reference work)
2015 2016 2017 2018
F : Works published in the time period - including L. cardiaca.
2. Composition of L. cardiaca
e composition of L. cardiaca was previously presented
by the EMA report [], consisting of furanic diterpenes
(labdanes), alkaloids (of special interest being stachydrine),
sterols, iridoids, avonoids, ursolic acid, minerals, and others.
Figure  presents the constituents of L. cardiaca and their
potential biomedical application, as presented by the pre-
literature sources.
e data briey presented in Figure  can be completed
with the ndings from the time period covered by the present
review.Ruschetal.[]identiedintheL. cardiaca extract the
presence of a chlorinated major iridoid glucoside (-chloro--
desoxy-harpagide), conrmed by ESI-MS and d/d H/C
NMR. Kuchta et al. [] quantied by RP-HPLC the presence
of ferulic acid, chlorogenic acid, caeic acid, cichoric acid,
rutoside, lavandulifolioside, verbascoside, and isoquercitrin
in L. cardiaca extract, as well as stachydrine in dierent parts
of L. cardiaca, included, for the rst time in literature, in the
fruits (.%) [, ].
e leaves essential oil was found to contain caryophyl-
lene, .%; 𝛼-humulene, .%; 𝛼-pinene, .%; 𝛽-pinene,
.%; linalool, .%; and limonene, .%, while the ursolic
acid present in the leaves was quantied to be .% (dry wt.)
Using HPLC-MS, Zhogova et al. [] quantied sev-
eral active compounds in both medicinal plant raw mate-
rial and medicinal preparation (harpagide, ajugol, galirido-
side, harpagide acetate, ajugoside, galiridoside, chlorogenic
acid, lavandulifolioside, verbascoside, rutin, hyperoside, iso-
quercitrin, and apigenin--O-glucoside).
An optimized recipe for the extraction of polysaccharides
from motherwort leaves was presented by Tahmouzi and
Ghodsi [], obtaining a yield of . ±.% for .C
extraction temperature, . min. extraction time, and .
ratio of water to raw material. Although the presence of
leonurine in the L. cardiaca extracts is presented by some
authors, including the previously cited report [, ], others
support the contrary, not identifying the compound in the L.
cardiaca extract [].
3. Biological Activities of L. cardiaca
e main biological activities of L. cardiaca can be divided in
several main categories.
3.1. Cardiovascular Action. e application of L. cardiaca
in cardiovascular disorders represents one of the main
applications of motherwort products []. Ritter et al. []
evaluated the cardiac and electrophysiological eects of
several types of L. cardiaca extracts by epicardial potential
mapping and by evaluation of the eect on the cardiac ion
currents using dierent types of cell models. e obtained
results suggested that L. cardiaca extractactsasamixed
ICa.L- (L-type calcium current), IKr- (rapid delayed rectier
current) antagonist, and If(funny current, recorded in
sinoatrial node cells from guinea pigs) modulator, support-
ing its application as an antianginal and antiarrhythmic
e cardioprotective potential of ursolic acid (the natural
pentacyclic triterpenoid carboxylic acid commonly found
in dierent L. cardiaca formulations) was demonstrated by
Liobikas et al. []. eir study revealed that the ursolic acid
induced uncoupling of oxidative phosphorylation in the h eart
mitochondria without aecting State  respiration rate, in
2O2production in isolated
mitochondria, in a dose-dependent manner. e uncoupling
of mitochondrial oxidation from phosphorylation, partial
inhibition of the mitochondrial respiratory chain, and a
reduction in the generation of free radicals in mitochondria
were also observed by Bernatoniene et al. [] in rat heart
mitochondria using L. cardiaca ethanol extracts.
BioMed Research International
Furanic labdane diterpenes
leocardin leosibiricin
leonurine Glycosides
Birthing aid
Women’s complaints
ursolic acid germacrene D chlorogenic acid
F : Composition and applications of L. cardiaca as emerging from pre- works (adapted from []).
e clinical trial conducted by Shikov et al. [] on
y patients treated with  mg L. cardiaca oil extract
per day for  days revealed signicant changes in systolic
blood pressure, diastolic blood pressure, heart rate, and
ECG for patients with stages  and  arterial hypertensions,
accompanied by an improvement of psychoemotional status
(anxiety, emotional liability, headache, and sleep disorders),
especially visible for stage  patients.
Stachydrine (alkaloid found in L. cardiaca)wasprovenby
Xie et al. [] to ameliorate homocysteine- (Hcy-) induced
endothelial dysfunction via nuclear factor erythroid –
related factor  (Nrf) dependent upregulation of guanosine
triphosphate cyclohydrolase I (GTPCH) and dihydrofolate
reductase (DHFR) enzymes and increase in bioavailabilities
of tetrahydrobiopterin (BH) and nitric oxide (NO), thus
protecting endothelial function.
e cardiotonic potential of L. cardiaca has been men-
tioned by Goetz [, ], Zaurov et al. [], Brenyo and Aktas
[], Kidd [], Jari´
c et al. [], Suroowan and Mahomoodally
[], Wang et al. [], Madridejos Mora [], Yarnell [],
Orhan et al. [], Dong et al. [], and Bianchi [].
3.2. Anti-Inammatory, Antimicrobial Eect, and Applica-
tion in Female Disorders. e anti-inammatory poten-
tial of leonurine (considered by some authors a natural
component of L. cardiaca []) on E. coli-induced mas-
titis in mice []: their results suggested that leonurine
alleviates the histopathological changes, downregulates the
levels of proinammatory cytokines (TNF-𝛼and IL-),
upregulates the level of anti-inammatory cytokine IL-,
and inhibits the expression of nitric oxide synthase (iNOS)
and cyclooxygenase- (COX-). e suggested mechanism
involves the inhibition of expression of toll-like receptor
(TLR)andnuclearfactor-kappaB(NF-𝜅B) activation
and mitogen-activated protein kinases (p), extracellular
signal-regulated kinase (ERK), and Jun N-terminal kinase
(JNK) phosphorylation. e anti-inammatory potential of
leonurine was also demonstrated by Liu et al. [] in rat
animal models of acute gouty arthritis. e obtained results
support the use of leonurine as COX-, mPGES- (microso-
mal prostaglandin E synthase-), and -LOX (-lipoxygenase)
inhibitor, leading to antiarthritis eects. In the same time,
amelioration of monosodium urate crystal-induced inam-
mation was achieved by decreasing interleukin-𝛽(IL-𝛽)
and tumor necrosis factor-alpha (TNF-𝛼)production.
e immunomodulatory potential of acetone/water
extract of L. cardiaca at a 𝜇g/ml concentration was
assessed by Sadowska et al. [], revealing a signicant
reduction of the platelet aggregation in the presence of
arachidonic acid, an application that could be benecial in
preventing inammatory lesions. In the same time, the tested
extract did not exhibit proapoptotic activity.
e traditional use of L. cardiaca as an anti-inammatory
and antimicrobial agent was also supported by the results
presented by Flemmig et al. []. ey tested several extracts
and components of L. cardiaca for their ability to regenerate
the pseudo-halogenating activity of lactoperoxidase (LPO).
e results supported the use of components with a ,-
dihydroxyphenylic partial structure (such as caeic acid
derivatives or phenylethanoids) as ecient LPO activity
BioMed Research International
regenerators, as well as the use of L. cardiaca ethanol extract
for the same application. e same study also presents the
isolation of the compound caeoylmalic acid, which also
revealed moderate LPO activity-regenerating eects.
Micota et al. [] studied the antimicrobial potential of L.
cardiaca acetone-water extract and its component ursolic acid
by determining the minimal inhibitory concentration, as well
as the antiadhesive and antibiolm properties against Staphy-
lococcus aureus strain (potential etiological agent of infective
endocarditis). eir results (MIC =  mg/ml for extract and
. mg/ml for ursolic acid) showed weak biostatic activity
of L. cardiaca extract in comparison to ursolic acid, but both
preparations possessed antiadhesive potential. e S. aureus
biolm formation was slightly inhibited by the extract (%),
but strongly inhibited by ursolic acid (%) at concentrations
of / MIC.
e study of Samoilova et al. [] on the eect of
subinhibitory doses of plant extract (including L. cardiaca)on
Escherichia coli biolm formation revealed that motherwort
extract showed a synergistic eect with sublethal concen-
tration of streptomycin ( 𝜇g/ml), inhibiting the specic
biolm formation. As the study was focused on the capacity
of low concentration plant extracts and p olyphenols to induce
adaptive mechanisms in E. coli,itcannotbeconsideredatruly
antimicrobial study.
Micota et al. [] used subinhibitory doses of L. car-
diaca extract to establish its eects on the characteristics
of Staphylococcus aureus. e benecial eect of the extract
was observed, such as reduction in staphylococcal adher-
ence, aggregates formation, coagulase activity, protein A
expression, or alpha-toxin synthesis. However, some of their
ndings (e.g., enhancement of staphylococcal tolerance to
exogenous hydrogen peroxide aer preincubation with the
extract) led to the conclusion of a possible risk of adverse
Wu et al. [] presented the application of leonurine
for ameliorating the inammatory responses in endometritis
model in mice. e leonurine treatment suppressed the
TNF-𝛼and IL-𝛽mRNA levels in uterus tissues, inhibited
lipopolysaccharide-induced TLR expression, and reduced
the phosphorylated p and I𝜅B𝛼proteins.
e clinical trial conducted by Denham et al. [] docu-
mented the herbal prescribing in usual practice, covering a
total of  herbs on  prescriptions (the most encountered
being L. cardiaca - %) for treatment of symptoms associated
with the menopause on  subjects. L. cardiaca was mainly
prescribed to control hot ushes, as a gynecological tonic and
as a relaxant.
going cesarean section, motherwort, in combination with
oxytocin, proved to be ecient for preventing postpartum
hemorrhage [].
Regarding the use of L. cardiaca in female disorders, the
plant is listed as a natural remedy for female reproductive
system (anxiolytic, antispasmodic, PMS, and menopausal
anxiety) [], as an emmenagogue, nervine, amenorrhea,
analgesic, and uterine astringents/vascular decongestants
and for treating adolescent dysmenorrhea [], for treating
menopausal anxiety, and as tranquilizer []. Lans et al.
[] present motherwort as a natural cure used in North
America from colonial times, due to its tonic, emmenagogue,
antispasmodic, and nervine properties, citing pre-
3.3. Antioxidant Action. e antioxidant activity of L. car-
diaca products was evaluated using several methods. Sad-
owska et al. [] evaluated the antioxidant potential of L. car-
diaca extract by ABTS, DPPH, and ferric reducing antioxi-
dant power assay, obtaining values of the antioxidant capacity
in the range ±–± 𝜇MTrolox/g.Ebrahimzadeh
et al. [] evaluated the antioxidant potential of Iranian
native L. cardiaca extract obtained from dried aerial parts by
percolation using methanol, by comparison with Grammos-
ciadium platycarpum and Onosma demawendicum extracts.
e results obtained by DPPHassay (IC50 =±.
mg/ml), iron reducing assay (results superior to vitamin
Cintheconcentration range-𝜇g/ml), nitric oxide-
scavenging assay (IC50 = . ±. mg/ml), metal chelating
assay (IC50 =±𝜇g/ml), and scavenging of hydrogen
peroxide (IC50 =.±. 𝜇g/ml) were correlated with the
total phenol content (. ±. mg gallic acid equivalent/g of
extract). Ebrahimzadeh et al. [] evaluated the correlation
between the total phenolic compounds and total avonoids
content and the nitric oxide scavenging properties for 
Iranian medicinal plants. e authors found good correlation
between total phenolic content (. ±. mg gallic acid
equivalent/g of extract) for L. cardiaca aerial parts methanol
extract, total avonoids content (. ±. mg quercetin
equivalents/g of extract), and nitric oxide radical scavenging
activity (IC50 = . ±. mg/ml).
Armatu et al. [] evaluated the antioxidant potential of
several extracts obtained from Romanian Lamiaceae species
(including L. cardiaca methanol extract) using the DPPH
assay, phosphomolybdenum method, and chemilumines-
cence assay in relationship with HPTLC ngerprints and
total phenolic content. e results obtained by the three
antioxidant assays at  mg/ml concentration (DPPH–%,
total antioxidant capacity –approx.  mg ascorbic acid
equivalents/g and % antioxidant activity for the chemilu-
minescence activity) were correlated with the relatively low
total phenolics content (. mg gallic acid equivalents/g of
Jafari et al. [] evaluated the total phenolic content and
antioxidant capacity (DPPHassay) of dierent fractions of
Iranian L. cardiaca extract. e best results were obtained for
the : metanolic-aqueous fraction (total phenolic content
.±. gallic acid equivalents/g of fraction and IC50 =
. 𝜇g/ml – DPPHassay).
e inuence of drying method was studied by Yi and
Wetzstein [] using three drying methods (greenhouse
sun-drying, C oven-drying, and Coven-drying)on
% methanol and % ethanol extracts from the leaves of
cultivated L. cardiaca plants. e best results were obtained
for ethanol extracts of C oven-dried plants (total polyphe-
nolics – approx.  mg/g GAE, Trolox-equivalent antioxidant
capacity – approx.  mM/g TE).
Polysaccharides from L. cardiaca extract exhibited a very
good scavenging activity of hydroxyl radicals (IC50 =.
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±. mg/mL), compared with vitamin C (IC50 =.±
. mg/mL) []. Wong et al. [] evaluated the antioxidant
obtained from Malaysian plants. e extract showed a rela-
tively good antioxidant potential (>% DPPHscavenging
activity at  mg/ml, >% NO scavenging activity at 
mg/ml, and >% metal chelating activity at  mg/ml) for
a phytochemical composition of . ±. mg GAE/g dry
weight (total phenolics), .±.mgQE/gdw(total
avonoids), and . ±. mg CAE/g dw (hydroxycinnamic
acids). e study of Ji et al. [] on the antioxidant eect of
plants with therapeutic potential on gynecological diseases
revealed no signicant inuence on the lag phase duration
of copper-induced low-density lipoprotein cholesterol (LDL-
C) oxidation, the authors suggesting as main reason for the
lack of antioxidant activity the solvent used for extraction.
Ziyatdinova et al. [] proposed an alternative method for the
evaluation of the antioxidant activity (determined as DPPH
inhibition using dierential pulse voltammetry) and com-
pared the values obtained for several medicinal plants with
those obtained spectrophotometrically. e results showed
better antioxidant eect for the L. cardiaca infusion (±%,
determined by dierential pulse voltammetry, respectively,
±%, determined by spectrophotometry) compared with
the tincture (% ethanol, .±.%, determined by dif-
ferential pulse voltammetry, respectively, ±% determined
by spectrophotometry). Ziyatdinova et al. [] described
a chronocoulometric method for the evaluation of the
antioxidant potential of  commercial-available medicinal
plants tinctures (including L. cardiaca), also establishing a
correlation between the antioxidant potential and the total
phenolics content. e evaluation revealed a relatively low
antioxidant capacity for the L. cardiaca tincture (.±. mg
e antioxidant potential of L. cardiaca extracts was also
briey presented in other works (for example, the works of
Sen and Chakraborty [] and Krishnaiah et al. []).
3.4. Other Applications. Motherwort was historically used
for the treatment of several nervous aictions, such as
depression, anxiety, or stress []. Romm [] classied L.
cardiaca as a natural remedy for the treatment of several aic-
tions, including postpartum depression, while the traditional
internal use of motherwort for the treatment of epilepsy was
documented by Adams et al. []. e potential towards the
treatment of anxiety and depressive disorders was evaluated
by Rauwald et al. [, ], by studying the eect of L. cardiaca
extract and constituents (isoleosibirin, R-chloro--desoxy-
harpagide, lavandulifolioside, stachydrine, and leonurine) on
the neuronal receptor gamma-aminobutyric acid (GABA).
e extract inhibited the concentration-dependent binding
of [()H]-SR to the GABA site of the GABA type
A receptor with a binding anity (IC50)of𝜇g/ml, sug-
gesting a potential neurological mechanism of action of
L. cardiaca, based on interaction to the GABA site of the
GABA type A receptor. e individual components tested
(except leonurine – IC50 -𝜇g/ml) did not exhibit signicant
activity. Commercially available leonurine was demonstrated
by Xu et al. [] to ameliorate LPS-induced acute kidney
injury in mice. e nephroprotective eect was expressed,
aer  days of treatment, by the values of reactive oxygen
species (ROS), malonyldialdehyde (MDA), and reduced glu-
tathione (GSH) which were reduced to near control levels,
while the lipopolysaccharide-induced tubular damage was
signicantly ameliorated, decreased renal injury biomarker
(KMI-), and inhibited the nuclear transfer of NF-𝜅Bp.
A similar nephroprotective eect was registered by Cheng
et al. [] in mouse unilateral urethral obstruction, by sup-
pressing ROS-mediated TGF-𝛽/Smad-induced tubulointer-
stitial brosis and inhibiting NF-𝜅B-mediated inammatory
response. Leonurine was also found to ameliorate cognitive
disfunction in rats’ model []. At a  concentration,
it was found to decrease the oxygen-glucose deprivation-
(OGD-) induced brain cell death to approx. % (fold of
control group), an approx. % reduction, compared with
the OGD group. Also, leonurine was found to alleviate
the impaired spatial learning and memory, as demonstrated
through Morris water maze test. Leonurine also decreased the
concentrations of glutamate and hydrogen peroxide in hip-
pocampus, ameliorated the impaired long-term depression
in hippocampus, improved cognitive function by modulating
the N-methyl-D-aspartate receptors-associated proteins, and
protected rats from bilateral carotid artery occlusion-induced
damage by inhibiting autophagy. e results suggested
leonurine as a potential drug candidate for chronic cerebral
Ethanolic extract obtained from aerial parts of L. cardiaca
was evaluated by Rezaee-Asl et al. [] as a potential analgesic,
using formalin, tail ick, and hot plate tests in mice. e
results of the study proved that at  mg/kg the extract
was able to reduce the formalin-induced pain in the early
phase, increase the antinociceptive activity, and signicantly
inuence the reaction time of the animals to the hot plates,
supporting the analgesic properties of the extract, action
mediated through peripheral, and central inhibitory mech-
e antiviral potential of L. cardiaca was reviewed by
Todorov et al. []. Dierent components of the extract were
found to be active against several types of viruses (ursolic
acid - HCV, HPV-; quearcetin - HSV-, poliovirus , RSV;
hyperoside – DHBV; apigenin – HSV-; rutin – HIV-), while
the chloroform and methanol extracts were presented to
possess antiherpes activity against HSV- and .
Onumah [] presents L. cardiaca as a potential adjuvant
in treating overactive thyroid, due to its action against
symptoms associated with hyperthyroidism (palpitations and
anxiety). Inhibition of the thyroid-stimulating hormone and
the reduction of excess production of thyroid hormones
were also presented by Shokri et al. [], the property being
assigned to its content in rosmarinic acid.
Unlike many other plant species, the evaluated liter-
ature data (even outside the time period covered by the
present review) presents no research regarding the phytosyn-
thesis of metallic nanoparticles using L. cardiaca extracts,
although the procedure was presented for L. japonicus
Table  summarizes the main biological activities pre-
BioMed Research International
T : Biological activities of L. cardiaca (-).
Origin Part of plant/product Typ e of
paper Activity Tests performed
responsible for
Against uterine
infection or other
tachyarrhythmia and
other cardiac
- Aerial parts Review Antioxidant -
Rutin and derivatives
of hydroxycinnamic
Aerial parts extract
(aqueous Soxhlet) and
rened extracts:
dichloromethane, %
Research Antianginal and
Epicardial potential
mapping, eect on the
cardiac ion currents
phenolic constituents []
available Ursolic acid Research Cardioprotective
Evaluation of
respiratory rates,
mitochondrial H2O2
generation, H2O2
antioxidant activity
Lithuania % ethanol extract Research Cardioprotective
Measurement of the
respiration rate and
mitochondrial H2O2
Chlorogenic acid and
avonoids orientin,
quercetin, hyperoside,
and rutin
- Soybean oil extract Clinical
Treatment of arterial
accompanied by
anxiety and sleep
dynamics of
symptoms; state –
activity – mood, the
Clinical Global
Impression scale, systolic
blood pressure, diastolic
blood pressure, heart
rate and ECG
Iridoids []
available Stachydrine Research endothelial function
Determination of cell
viability, Nitric oxide
assay, Measurement of
BH, Measurement of
cGMP levels in rat
arterial rings.
Measurement of
Quantitative reverse
(qRT-PCR), Western
- Extract Review Sedative, cardiotonic - []
- Aerial parts extract Review
bradycardic agent,
- Aerial parts tincture Review
decreases arterial
pressure and
strengthens the
contraction of uterus
BioMed Research International
T  : C o n t i n u ed.
Origin Part of plant/product Typ e of
paper Activity Tests performed
responsible for
Protective eect in
myocardial ischemia
- Lavandulifolioside Review chronotropic eects - - []
- - Review Cardiovascular - - []
- Aerial parts, tea Review
Strengthening the
heart, arrhythmia,
Cardiac arrhythmias,
tachycardia, heart
glycosides []
antioxidant --[]
relief of nervous
tension symptoms,
treatment of
maintenance of
normal cardiac
available Leonurine Research Anti-Inammatory
analysis, Cytokines
Analysis, Quantitative
Real-Time Polymerase
Chain Reaction, Western
Blot Analysis
available Leonurine Research Agent for gouty
arthritis treatment
examination, Lentiviral
transduction, Western
blot analysis, Cytokine
available, Poland
Acetone-water (:,
v/v) extract Research Immunomodulatory,
NO production in
Human umbilical vein
endothelial cells, platelet
aggregation, ABTS,
DPPHand FRAP assay
- []
Ethanol extract (%),
Soxhlet extraction,
Methanol extract, other
and antimicrobial
Eect of extracts and
single components on
lactoperoxidase activity
Phenolic components
available, Poland
Leaves acetone-water
(:, v/v) extract Research Antimicrobial
Evaluation of
anti-adhesive and
anti-biolm properties
against S. aureus
Iridoid glycosides, di-
and triterpenoids,
avonoids, tannins
and volatile oils
BioMed Research International
T  : C o n t i n u ed.
Origin Part of plant/product Typ e of
paper Activity Tests performed
responsible for
available, Russia Aerial parts water extract Research Anti-biolm
formation Biolm formation assay - []
available, Poland
Aerial parts
Eect of
extracts on S. aureus
S. aureus survival,
staphylococcal tolerance
to oxidative stress, S.
aureus 𝛼-toxin (Hla)
release and protein A
(SpA) expression,
aggregation in human
plasma, Fibrinogen
polymerization and S.
aureusadhesion to brin
available Leonurine Research Anti-inammatory
analysis, Cell viability
assay, Analysis of
cytokines, qRT-PCR
- Aerial parts, tea Clinical
To control h o t  u s h e s ,
gynaecological tonic,
- Motherwort injection Trial
Mean blood loss,
postpartum hemorrhage,
mean systolic blood
pressure, diastolic BP,
heart rate, respiratory
rate, hemoglobin and
platelet count, incidence
of postpartum
hemorrhage, safety
antispasmodic, PMS,
and menopausal
Aerial parts, tea,
tincture, infusion Review
anxiolytic, uterine
-Aerial parts, tincture,
tea, infusion Review
Menopausal anxiety,
insomnia, palpitations
-Aerial parts, infusion,
decoction Review
Tonic, Amenorrhoea,
suppressed lochia,
Aerial parts, methanol
extract Research Antioxidant, radical
activity, reducing power,
nitric oxide-scavenging
activity, Metal chelating
activity, ferric
thiocyanate assay,
Scavenging of hydrogen
Phenolic compounds []
BioMed Research International
T  : C o n t i n u ed.
Origin Part of plant/product Typ e of
paper Activity Tests performed
responsible for
Aerial parts, methanol
and water extracts Research Antioxidant Nitric oxide radical
scavenging activity
Phenolic compounds,
avonoids []
Aerial parts, methanol
extract Research Antioxidant, free
scavenging potential
reduction assay, DPPH
Polyphenolics []
Cultivated, Iran Aerial parts, extracts and
fractions Research Antioxidant DPPHassay Phenolic compounds []
Leaves, % methanol or
% ethanol Research Antioxidant ABTSassay Phenolic compounds []
Leaves, polysaccharides
extract Research Antioxidant,
Hydroxyl radical
scavenging capacity,
antimicrobial eect
evaluated by the lter
disk diusion plate
method against bacteria,
yeast and fungi
Polysaccharides []
Aerial parts, water
extract Research Antioxidant,
DPPHassay, nitric
oxide radical scavenging
assay, metal chelating
inhibition assay
Phenolic compounds []
available, China
Aerial parts, aqueous
extract Research Antioxidant LDLc oxidation delay - []
available, Russia
Commercial tinctures
and infusions Research Antioxidant
voltammetry and
available, Russia Commercial tinctures Research Antioxidant Chronocoulometry
phenolic acids, caeic
acid -rutinoside,
- Methanol extract Review Antioxidant DPPHassay Flavonoid and
phenolic glycosides []
- Aerial part, tincture, tea Review Nervine relaxant,
anxiolytic, --[]
- - Review Epilepsy treatment - - []
Aerial parts, %
ethanol extract,
Stachydrine, Leonurine,
Isoleosibirin, R-chloro-
Treatment of anxiety,
nervousness, sedative
In vitro GABA receptor
binding assays, -[,]
available Leonurine Research Nephroprotective
Measurement of TNF-𝛼,
IL-, IL-, IL-,
Measurement of serum
creatinine and blood
urea nitrogen, Assay of
GSH, Assay of ROS,
Assay of MDA level,
Western blot analyses,
Protein assay,
Histological assay
 BioMed Research International
T  : C o n t i n u ed.
Origin Part of plant/product Typ e of
paper Activity Tests performed
responsible for
available Leonurine Research Nephroprotective
Measurement of TGF-𝛽,
level, ROS assay, Assay
of MDA level, Assay of
GSH level, Western blot
analyses, Protein assay,
Histological assay
available Leonurine Research Neuroprotective
Evaluation of spatial
learning and memory
performances of rats,
levels of glutamate and
H2O2of hippocampus,
Western blot assay
-Aerial parts, ethanolic
extract Research Analgesic Nociceptive Behavioral
Tests -[]
-Aerial parts, dierent
types of extracts Review Antiviral -
ursolic acid,
quercetin, hyperoside,
glucoside, rutin
Treatment of
palpitations, anxiety
Treatment of
hyperthyroidism -Rosmarinicacid[]
4. Dosage and Toxicology
As previously has been presented, L. cardiaca preparations are
currently used in the treatment of several conditions. Relative
to commercial products, the EMA report cited [] presents
them to be safe, suggesting a duration of use limited to four
weeks. e report also presents the adverse eects of an intake
of . grams of a powdered extract per day (diarrhea, uterine
bleeding, and stomach irritation). L. cardiaca is listed as a
“herb to avoid during pregnancy” [, ], mainly due to its
emmenagogue and uterine stimulation properties. Kaye et
al. [] listed L. cardiaca as a “herbal drug associated with
bleeding abnormalities”, an aspect to be considered by the
anesthesia practitioner.
on et al. [] presented the reduction of platelet
aggregation and brinogen levels upon intravenous adminis-
tration of motherwort. L. cardiaca also potentiates antithrom-
botic and antiplatelet eects, increasing the risk of bleed-
ing. When administered concomitant with benzodiazepines,
motherwort can also have a synergistic sedative eect result-
ing in coma [].
L. cardiaca was also presented to potentialize the eect of
warfarin, by inhibiting platelet aggregation [].
Related to individual compounds, data are scarce and
mainly outside the current review time period: Milkowska-
Leyck et al. presented moderate toxicity of lavandulifo-
lioside (LD50 approx.  mg/kg) and n-butanol extract
(LD50 approx.  mg/kg) for intravenous administration,
while for oral administration, the toxicity was much lower
(LD50 > mg/kg) []; Mitchell and Rook [] present
the potential of L. cardiaca leaves to cause photosensitization
and dermatitis; herbal intravenous injection has a LD50 of
- mg/kg (mice), while the intravenous LD50 of the total
alkaloids of the herb was approx.  mg/kg, while the
minimal lethal dose of leonurine in frogs (subcutaneous
administration) was - mg/kg []. Due to the lack
in scientic evidences, most of the sources presenting tra-
ditional use of motherwort suggest the strict following of
relevant directions on products containing L. cardiaca and
the requesting supplemental information from pharmacists,
physician, or other healthcare professionals before use [].
Some chemical components from L. cardiaca aerial parts
(pyrrolidine alkaloids, such as stachydrine, cyclic peptide,
such as cycloleonurinine or labdane diterpenes, such as
leosibiricin) are considered “chemicals of concern” for human
health when used in food and food supplements [].
5. Conclusions
e use of motherwort (Leonurus cardiaca L.) has been
documented since ancient times, especially as a cardiotonic
and for the treatment of gynecological conditions. e com-
position (dominated by furanic diterpenes, alkaloids, sterols,
activity, with cardioprotective, antioxidant, antimicrobial,
anti-inammatory, analgesic, nephroprotective, and antiviral
properties, among others.
e current study aimed to present the progress made
in the study of motherwort from the date of the European
Medicine Agency “Assessment report on Leonurus cardiaca
BioMed Research International 
L., herba”. According to our ndings, most of the literature
data focuses on cardioprotective and antioxidant potential of
L. cardiaca, although the data also suggest the exploration of
new applications. is, in turn, would be a promising research
area for future studies. Future research should also be focused
on a denitive conclusion regarding the composition of
motherwort (especially the presence of leonurine), as well as
the opening of new research directions, such as the use of L.
cardiaca extracts in nanotechnology (for the phytosynthesis
of nanoparticles).
Conflicts of Interest
e authors declare no conicts of interest.
Authors’ Contributions
All authors contributed equally to data collection and analy-
sis, and manuscript design. Irina Fierascu and Radu Claudiu
Fierascu prepared and revised the manuscript.
e authors gratefully acknowledge the support obtained
through the project SusMAPWaste, SMIS , Contract
No. /.., from the Operational Program Compet-
itiveness -, project conanced from the European
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... The literature provides significant scientific data on the study of the chemical composition of motherwort herb (Leonurus cardiaca L.) [1,13,14], root/rhizome of valerian (Valeriana officinalis L.) [2], fruit, leaves with flowers of hawthorn (Crataegus genus) [3]. For example, the structures of about 300 substances have been isolated and determined from the motherwort (Leonurus genus) [13,14]. ...
... The literature provides significant scientific data on the study of the chemical composition of motherwort herb (Leonurus cardiaca L.) [1,13,14], root/rhizome of valerian (Valeriana officinalis L.) [2], fruit, leaves with flowers of hawthorn (Crataegus genus) [3]. For example, the structures of about 300 substances have been isolated and determined from the motherwort (Leonurus genus) [13,14]. They are represented by alkaloids, monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, iridoids, flavonoids, phenylpropanoids, steroids, cyclic peptides, etc. ...
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Objective: To substantiate the possibility of using polarimetry to control the quality of tinctures as an additional pharmacopoeial method. Methods: The polarimetric method (POL-1/2, Atago, Japan, the measurement accuracy of±0.002 °) was used to measure the optical activity (α °) of motherwort, valerian and hawthorn tinctures. The dynamic light scattering method (DLS; Zetasizer Nano ZS, Malvern, UK) was used to assess the stability of alcoholic and aqueous dilutions of tinctures according to the intensity of dynamic light scattering dependent on the size (d, nm) of the dispersed phase particles and the values of the electrokinetic potential (ξ, mV). Results: For the first time in this investigation, the polarimetry approach was proposed to evaluate the cardiotonic and hypotensive tinctures' quality and for their identification. Valerian tincture, dilution 1:40,-0.10°<α°<-0.89°; motherwort, tincture-dilution 1:10,-0.10°<α°<-2.21°; hawthorn, tincture without dilution,-0.76°<α°<-1.55°-these are the acceptable ranges of optical activity (α°) of their alcohol dilutions. Beyond these intervals, the use of the polarimetric approach is impossible. Values of optical activity below 0.1 correspond to too low a content of optically active components. Tinctures with optical activity above the upper value of the interval were unstable dispersed systems with low values of the electrokinetic potential (|ξ|≪25mV) and micron particle sizes. Reference tinctures were made from raw materials (Leonurus cardiaca L.) to verify the results. The quality parameters: optical activity (α°), spectra of dynamic light scattering by intensity, volume, and number ("I-d"; "V-d"; "N-d"), electrokinetic potential (ξ) values, and photon pulse count per second (Count Rate, kcps) corresponded to the results obtained for pharmaceutical dosage forms. Conclusion: The permissible intervals of optical activity (α°) of their ethanol dilutions, as well as their relationships with the particle size of the dispersed phase and the values of the electrokinetic potential, were established for the first time to evaluate the quality of tinctures. The obtained results show that polarimetry can be recommended as an additional pharmacopoeial quality control method for tinctures.
The impacts of nZVI and iron oxides on growth, physiology and elicitation of bioactive antioxidant metabolites in medicinal aromatic plants must be critically assessed to ensure their safe utilization within the food chain and achieve nutritional gains. The present study investigated and compared the morpho-physiological and biochemical changes of Leonurus cardiaca L. plants as affected by various concentrations (0, 250, 500 and 1000 mg L⁻¹) of nZVI and Fe3O4. The foliar uptake of nZVI was verified through Scanning Electron Microscopy (SEM) images and Energy Dispersive X-ray (EDX) analytical spectra. Plants exposed to nZVI at low concentration showed comparatively monotonic deposition of NPs on the surface of leaves, however, the agglomerate size of nZVI was raised as their doses increased, leading to remarkable changes in anatomical and biochemical traits. 250 mg L⁻¹ nZVI and 500 mg L⁻¹ Fe3O4 significantly (P < 0.05) increased plant dry matter accumulation by 37.8 and 27% over the control, respectively. The treatments of nZVI and Fe3O4 at 250 mg L⁻¹ significantly (P < 0.01) improved chlorophyll a content by 22.4% and 15.3% as compared to the control, and then a rapid decrease (by 14.8% and 4.1%) followed at 1000 mg L⁻¹, respectively. Both nZVI and Fe3O4 at 250 mg L⁻¹ had no significant impact on malondialdehyde (MDA) formation, however, at an exposure of 500–1000 mg L⁻¹, the MDA levels and cellular electrolyte leakage were increased. Although nZVI particles could be utilized by plants and enhanced the synthesis of chlorophylls and secondary metabolites, they appeared to be more toxic than Fe3O4 at 1000 mg L⁻¹. Exposure to nZVI levels showed positive, negative and or neutral impacts on leaf water content compared to control, while no significant difference was observed with Fe3O4 treatments. Soluble sugar, total phenolics and hyperoside content were significantly increased upon optimum concentrations of employed treatments-with 250 mg L⁻¹ nZVI being most superior. Among the extracts, those obtained from plants treated with 250–500 mg L⁻¹ nZVI revealed the strong antioxidant activity in terms of scavenging free radical (DPPH) and chelating ferrous ions. These results suggest that nZVI (at lower concentration) has alternative and additional benefits both as nano-fertilizer and nano-elicitor for biosynthesis of antioxidant metabolites in plants, but at high concentrations is more toxic than Fe3O4.
Endometriosis is one of the most common gynecological diseases, which often takes 8-10 years to diagnose. Integrative Chinese Medicine (ICM) brings together the best of modern phytopharmacology, Chinese Medicine and conventional medicine. Early therapy of endometriosis with western medicinal plants in ICM according to Jeremy Ross can not only treat pain but improve the quality of life and prevent chronification.
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This paper serves to fill a gap in the literature regarding evidence for the use of botanical remedies in the promotion of fertility. It examines the botanical remedies that were used in North America (1492–1900) for all stages of reproduction from preconception to birth, and discusses their potential for future use with present-day infertility treatments. Each medicinal plant discussed in this paper is assessed using an ethnomedicinal methodology that entails examining the published ethnobotanical, phytochemical and pharmacological data. A few clinical trials have shown that there is potential for medicinal plants to improve the success rate of assisted reproductive technology (ART) treatment if used in an integrated manner, similar to the integrated use of traditional Chinese medicine with ART treatment. For example, research has shown that older women who become pregnant have a high miscarriage rate, and this is one area that complementary and alternative medicines can address.
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Background Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for gynecological and cardiovascular disorders. This study is aimed to examine the effects of STA on homocysteine (Hcy)-induced endothelial dysfunction. Methods The effects of STA on vascular relaxation in rat thoracic aortas (TA), mesenteric arteries (MA) and renal arteries (RA) were measured by using Multi Myograph System. The levels of nitric oxide (NO), tetrahydrobiopterin (BH4) and guanosine 3′, 5′ cyclic monophosphate (cGMP) were determined. Endothelial nitric oxide synthase (eNOS) dimers and monomers were assayed by using Western blotting. GTP cyclohydrolase 1 (GTPCH1) and dihydrofolate reductase (DHFR) expressions were measured by using quantitative reverse transcriptase-PCR (qRT-PCR) and Western blotting. Results STA effectively blocked Hcy-induced impairment of endothelium-dependent vasorelaxation in rat TA, MA and RA. STA-elicited arterial relaxations were reduced by NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the NO-sensitive guanylyl cyclase inhibitor 1H- [1, 2, 4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not by inducible iNOS inhibitor 1400 W nor the nonselective COX inhibitor indomethacin. Hcy caused eNOS uncoupling and decreases in NO, cGMP and BH4, which were attenuated by STA. Moreover, STA prevented decreases of GTPCH1 and DHFR levels in Hcy-treated BAECs. Conclusion We demonstrated that STA effectively reversed the Hcy-induced endothelial dysfunction and prevented eNOS uncoupling by increasing the expression of GTPCH1 and DHFR. These results revealed a novel mechanism by which STA exerts its beneficial vascular effects. Electronic supplementary material The online version of this article (10.1186/s10020-018-0010-0) contains supplementary material, which is available to authorized users.
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Background Little information is available concerning antioxidant effects of plant teas (water boiled) which are used more commonly in traditional Chinese medicine than other extracts. Thus, we addressed this issue by evaluating the ability of teas from four different plants with therapeutic potential on gynecological diseases. Methods The aqueous extracts of Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria rhizome were prepared and then their effects on copper-induced low-density lipoprotein cholesterol (LDL-C) oxidation were evaluated by spectrophotometric method. Density gradient ultracentrifugation method was recruited to isolate LDL-C from healthy individuals. ResultsOur results showed that adding 10, 20, and 30 µl S. persicae could increase the lag phase duration of LDL-C oxidation compared with control reaction 12, 21, and 33%, respectively. The most effective delay (87%) was observed when 30 µl H. diffusa was added to the reaction. In cases of L. cardiaca and C. zedoaria, we found no significant influence on the lag phase duration (p > 0.05). Moreover, our findings about starting point of the decomposition phase were almost in parallel with the lag phase results, as 30 µl of S. persicae or H. diffusa teas could significantly increase the initiation time of decomposition (p < 0.05). Conclusions In conclusion our results showed that both S. persicae and H. diffusa teas and not L. cardiaca and C. zedoaria could have medicinal therapeutic effects partly through direct oxidation prevention.
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Historically Russia can be regarded as a “herbophilious” society. For centuries the multinational population of Russia has used plants in daily diet and for self-medication. The specificity of dietary uptake of medicinal plants (especially those in the unique and highly developed Russian herbal medical tradition) has remained mostly unknown in other regions. Based on 11th edition of the State Pharmacopoeia of the USSR, we selected 70 wild plant species which have been used in food by local Russian populations. Empirical searches were conducted via the Russian-wide applied online database, library catalogs of public libraries in St-Petersburg, the databases Scopus, Web of Science, PubMed, and search engine Google Scholar. The large majority of species included in Russian Pharmacopoeia are used as food by local population, however, aerial parts are more widely used for food. In this review, we summarize data on medicinal species published in Russia and other countries that are included in the Russian Pharmacopoeia and have being used in food for a long time. Consequently, the Russian Pharmacopoeia is an important source of information on plant species used traditionally at the interface of food and medicine. At the same time, there are the so-called “functional foods”, which denotes foods that not only serves to provide nutrition but also can be a source for prevention and cure of various diseases. This review highlights the potential of wild species of Russia monographed in its pharmacopeia for further developing new functional foods and—through the lens of their incorporation into the pharmacopeia—showcases the species' importance in Russia.
Herbs have been long known to provide health-promoting benefits and are demonstrated to have antioxidant, anti-inflammatory, antibacterial, analgesic, and antitumor activities. This study evaluated the effects of drying conditions and extraction protocols on the biochemical activity of three culinary and medicinal herbs: rosemary ( Rosmarinus officinalis ), motherwort ( Leonurus cardiaca ), and peppermint ( Mentha piperita ). Leaf tissues were dried by sun, oven-dried at 40 °C, or oven-dried at 70 °C and extracted using 80% methanol or 80% ethanol. Total polyphenol (TPP) using the Folin-Ciocalteu reagent method and antioxidant capacity using the Trolox-equivalent antioxidant capacity (TEAC) assay were determined. Both drying and extraction conditions significantly impacted TPP content and TEAC in the three herb species. Sun-dried or 40 °C oven-dried herbs exhibited significantly higher TPP content and TEAC capacity than fresh samples, suggesting low-temperature drying may be a good postharvest means to store medicinal/culinary herbs. Exposure to 70 °C oven-drying caused significant antioxidant loss. In addition, the current study showed that with fresh tissue, 80% ethanol extraction had significantly higher TPP and TEAC than 80% methanol extraction for all three herbs, yet for dried herbs, the efficacy of ethanol/methanol extraction varied with different drying treatments.
The thyroid gland regulates a wide range of physiological activities such as growth, metabolism, homeostasis, and cell proliferation and differentiation through the secretion of thyroid hormones (THs). Thyroid diseases are among the most common endocrine disorders, hypothyroidism is the most common clinical thyroid dysfunction. Hyperthyroidism means increased thyroid function and refers to excess metabolic state due to excessive synthesis and secretion of TH. Medicinal plants have been identified and used by humans throughout history. To name the herbs and natural antioxidants used to treat thyroid disorders including hypothyroidism and hyperthyroidism. Related articles were obtained using the Google Scholar, PubMed, and ScienceDirect databases. The results of this study indicate that medicinal plants include Fucus vesiculosus, Aegle marmelos, Coleus forskohlii, Linum usitatissimum, Withania somnifera, Commiphora mukul, Nigella sativa, and Bacopa monnieri. They can improve the hyperthyroidism in improving hyperthyroidism and herbal remedies, Melissa officinalis A. marmelos, Lycopus europaeus, Leonurus cardiaca, and Aloe barbadensis be effective. Herbal drugs cause comparatively fewer side effects. It is believed that the drugs derived from the plants are very safe and produce significant effects in the treatment of various diseases. Today, traditional medicine is being widely used and plants are still considered a major source of natural antioxidants that can serve as a clue for the development of new drugs.
The oxidation potentials of medicinal plant tinctures have been studied on glassy carbon electrode, modified layer-by-layer with multi-walled carbon nanotubes and poly(gallic acid) (PGA/MWNT/GCE) in phosphate buffer solution of pH 7.4. PGA-modified electrode has shown significantly higher sensitivity towards antioxidants in tinctures in comparison to bare GCE and MWNT/GCE. A novel approach for the evaluation of antioxidant capacity of medicinal plant tinctures using one-step chronocoulometry at 1.0 V has been developed. A steady state is achieved at 100 s of electrolysis. The antioxidant capacity has been expressed in quercetin equivalents per 1 mL of tincture. Linear dynamic ranges of 0.010–0.25 and 0.25–250 μmol L−1 quercetin with the limits of detection and determination of 2.9 and 9.8 nmol L−1, respectively, have been obtained. Eleven medicinal plant tinctures have been investigated. The antioxidant capacity decreases in the following order: Rhodiola rosea L. > Paeonia anomala L. > Aralia elata var. mandshurica (Rupr. & Maxim.) J. Wen > Echinacea purpurea (L.) Moench ≈ Schisandra chinensis (Turcz.) Baill. > Valeriana officinalis L. ≈ Leonurus cardiaca L. > Mentha piperita L. > Calendula officinalis L. > Crataegus spp. > Panax ginseng C. A. Meyer. Strong positive correlations of the antioxidant capacity of tinctures with the antioxidant activity and total phenolics (r = 0.9715 and 0.9738, respectively, at rcrit = 0.602, α = 0.05 and n = 11) confirm the accuracy of the developed chronocoulometric method.
Endometritis is the inflammation of the endometrium that is associated with lower conception rates, increased intervals from calving to first service, and more culls for failure to conceive, which leads to serious economic losses in the dairy industry. Leonurine, a natural active compound of Leonurus cardiaca, has been proved to possess various biological activities. However, there is still no study about its anti-inflammatory effects on LPS-induced endometritis. The present study aimed to demonstrate the underlying mechanism responsible for the anti-inflammatory effects of leonurine on LPS induced endometritis in mice and in bovine endometrial epithelial cells (bEECs). The results of pathological section displayed that leonurine alleviated LPS induced uterine injury. qRT-PCR and ELISA experiments suggested that leonurine inhibited the expression levels of TNF-α and IL-1β in uterus tissues and bEECs. Molecular studies showed that TLR4 expression and nuclear factor (NF)-κB activation were both inhibited by leonurine treatment. These results suggested that the therapeutic effects of leonurine on LPS-induced endometritis in mice and bEECs may act by inhibiting the expression of TLR4 and its downstream mediated NF-κB pathway. Accordingly, leonurine may serve as an effective drug in preventing and treating LPS induced endometritis.
Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase-1 (mPGES-1)-derived eicosanoids play an essential role in human inflammatory disorders. Here, we investigated whether inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate (MSU) crystal-induced inflammation. Virtual screening assay and in vitro enzyme inhibition assay showed that leonurine was a potential inhibitor of COX-2, mPGES-1 and 5-LOX. Compared with COX-2 inhibitor celecoxib, leonurine (30 mg/kg) significantly decreased ankle perimeter, gait score and neutrophil number in synovial fluid in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, mPGES-1 and 5-LOX and production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the synovial fluid macrophages. In addition, leonurine decreased representative M1 marker (iNOS and CD86) expression, NLRP3 inflammasome activation and M1 cytokine (TNF-α and IL-1β) production. In the in vitro cultured RAW264.7 and human monocyte-derived macrophages (MDMs), blockade of COX-2/mPGES-1 and 5-LOX by leonurine inhibited macrophage M1 polarization and NLRP3 inflammasome activation in response to MSU crystals, and thus down-regulated IL-1β and TNF-α with STAT1 and NF-κB inactivation. Conversely, these effects were partially abolished by overexpression of COX-2, mPGES-1, 5-LOX or STAT1. Furthermore, leonurine prevented a positive feedback loop between COX-2/mPGES-1/5-LOX and IL-1β/TNF-α in MSU crystal-induced inflammation. Together, simultaneous down-regulation of COX-2/mPGES-1 and 5-LOX by leonurine ameliorates MSU crystal-induced inflammation through decreasing IL-1β and TNF-α production. Our study may provide novel multi-target agents toward the arachidonic acid (AA) network for gouty arthritis therapy.
This book is a detailed guide to a new integrative approach to the prevention and treatment of various cardiac disorders and risk factors, including coronary artery disease, congestive heart failure, arrhythmias, dyslipidemia, and hypertension. This approach combines various strategies, including metabolic cardiology, low-dose medicine, exercise programs, stress management programs, evaluation for inherited risk factors, and various other healing modalities. Metabolic cardiology focuses on the prevention, management, and treatment of cardiovascular disease at the cellular level through biochemical interventions with nutritional supplements that can promote energy production in the heart. Low-dose medicine, on the other hand, interprets pathological phenomena as an imbalance in intercellular signaling that may be corrected through the administration of low physiological doses of messenger molecules. Therapies outside of mainstream medicine may also be deployed in integrative cardiology, for example acupuncture, herbal medicine, and homeopathy. Integrative Cardiology will be of interest to all practitioners wishing to learn about an approach that incorporates the incredible advances in medication and technology with a focus on nutrition, lifestyle, and mind–body influences.