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Corresponding author: Ali Esmail Al-Snafi
Department of Pharmacology, College of Medicine, University of Thi qar, Iraq.
Copyright © 2022 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0.
Medicinal plant affected respiratory, gastrointestinal, vascular and uterine smooth
muscle contractility
Ali Esmail Al-Snafi *
Department of Pharmacology, College of Medicine, University of Thi qar, Iraq.
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
Publication history: Received on 12 March 2022; revised on 14 April 2022; accepted on 16 April 2022
Article DOI: https://doi.org/10.30574/gscbps.2022.19.1.0148
Abstract
In the current review, PubMed, Web Science, Science Direct, and Scopus were searched to investigate the medicinal
plants which contracted or relaxed the respiratory, gastrointestinal, vascular and uterine smooth muscles with
emphasis on their mode of action.
Keywords: Respiratory; Gastrointestinal; Vascular; Uterine; Smooth Muscles; Contraction; Relaxation
1. Introduction
In a healthy body, the process of contraction of smooth muscle cells is regulated mainly by activation of receptors and
mechanical stimulation (stretching) of contractile proteins. A change in the membrane potential, caused by the release
of an action potential or by activation of stretch-dependent ion channels in the plasma membrane, can lead to
contraction. Smooth muscle relaxation occurs either as a result of removal of the contractile stimulus or by the direct
action of a substance that stimulates inhibition of the contractile mechanism. Regardless, the process of relaxation
requires a decreased intracellular Ca2+ concentration and increased MLC phosphatase activity (1-2). Medicinal plants
induced contraction or relaxation of smooth muscles by many mechanisms included interference with
neurotransmitters, neuro-mediators, second messengers, ionic channels and other mechanisms (3-8). The current review
focused on medicinal plants affected the function of vascular, respiratory, uterine and gastrointestinal smooth muscles.
Table 1 Medicinal plant affected respiratory smooth muscle contractility
Ref
Action
Model
Extract or
compounds
Medicinal
plant
9
Five alk(en)ylsulfinothioic acid alk(en)yl-esters
isolated from onions inhibited allergen- and PAF-
induced bronchial obstruction of guinea-pigs.
Bronchial
tissue of
guinea-pigs
Five alk(en)yl
sulfinothioic
acid alk(en)yl-
esters isolated
from onion
Allium cepa
10-
11
Benzyl-isothiocyanate (BITC) inhibited BO in a dose-
dependent fashion: 150 mg/kg: 89%; 75 mg/kg: 76%;
30 mg/kg: 66%; 15 mg/kg: 49%. Ethyl-isothiocyanate
and allyl-isothiocyanate showed similar effects, while,
p-hydoxy-benzyl-isothiocyanate, was ineffective.
Bronchial
obstruction
induced by
inhalation of
ovalbumin
Isothiocyanate
compounds
isolated from
onion
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
203
in guinea-
pigs
12-
13
Allium cepa extract caused relaxation of tracheal rings,
and a reduction in total number of cells in broncho-
alveolar lavage and eosinophil peroxidase in lungs.
Effects on
cytokine and
on smooth
muscle
contraction
in vitro and
its
therapeutic
potential in a
murine
model of
asthma
Extract
obtained by
maceration
14
It induced a dose-dependent relaxation with recorded
EC50 values of 71.87 ± 5.90 μg/ml. Pre-treatments with
mepyramine (10−7 M), methysergide (10−7 M), caffeine
(10−6 M), theophylline (10−6 M), nifedipine (10−6 M),
and dipyridamole (10−6 M) did not alter Allium sativum
bulb aqueous extract Concentration-response curves
were significantly shifted toward right in the presence
of aspirin (3.10−3 M), indomethacin (10−6 M), prazosin
(10−6 M), and propranolol (10−7 M).
Isolated
smooth
muscle of
trachea of
rats
Aqueous bulb
extract
containing
0.06%-0.10%
of allicin
Allium
sativum
15-
16
Khella’s antispasmodic properties are also useful to
treat asthma attacks. During the 1950′s, research into
khella’s usefulness as an asthma treatment led to the
creation of many asthma medications containing
khellin and visnagin
Clinical
Khella raw fruit
Ammi visnaga
17-
19
It showed significant spasmolytic activity on tracheal
muscle of cat.
Tracheal
muscle of cat
Alcoholic
extract of the
aerial parts
Andrachne
aspera
20-
21
In an open clinical study carried out on 54 patients with
chronic bronchial asthma, it showed anti-asthmatic
effects, it caused significant elevation in the values of
forced expiratory volume in first second (FEV1%) and
forced volume capacity (FVC) with marked reduction in
asthmatic attacks.
Clinical
Chamomile
was boiled and
immediately
used by
inhalation for
5-10 minutes
using vapor
machine
Anthemis
nobelis
22
The plant extract (500 and 700 μg/ml) significantly (P <
0.05) depressed and shifted the calcium concentration-
response curves (1 × 10-3- 1 × 10-1 M) to rightward
similar to that of nifedipine.
Guinea -pig
trachea in
calcium free
high K+-
MOPS-PSS
Ethanol extract
Bacopa
monnieri
23-
24
It exhibited potent activity comparable to disodium
cromoglycate, a known mast cell stabiliser.
Mast cell
stabilization
Methanolic
fraction
25-
26
50, 100 and 200 μg/ml of the extract showed a dose-
dependent direct relaxant activity.
Tracheal
smooth
muscle chain
of Guinea-
pig
Aqueous
extract
Calotropis
procera
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
204
27-
28
The broncho-dilatory effects were studied by
examining the relaxant effects on pre-contracted by 10
/μM methacholine (M) of the isolated tracheal chains of
guinea pigs. The broncho-dilatory effect of AE, ME, and
EO was lower than that of theophylline (p<0.00l), but it
was significantly higher than the effect of saline (p<0.05
for AE, p<0.01 for ME, and p<0.005 for EO). The
broncho-dilatory effect was mainly due to the non-
competitive antagonistic property at muscarinic
receptors. The β- stimulatory effect and/or anti-
histaminic effect of EO might be contributed to its non-
competitive property.
Isolated
tracheal
chains of
guinea pigs
Aqueous
extract (AE),
macerated
extract (ME)
and essential
oil (EO)
Carum carvi
29-
30
The extracts of wood and bark inhibited the histamine
induced contraction of trachea (10-80 mcg/ml) in dose
dependent pattern (P<0.05) while leaf and fruit
extracts were without any effects. The successive
chloroform extract demonstrated more activity (63.30
± 10.33) as compare to petroleum ether (87.5 ± 13.24)
and methanolic extract (166.66 ± 23.32) of wood
(P<0.05). The chronic treatment of methanolic wood
extract (100 mg/kg, ip) significantly reduced the
clonidine induced catalepsy at 60 and 120 minutes
(P<0.05) and mast cell degranulation (72.50±8.37)
against standard, disodium cromoglycate, (85.19 ±
4.30) (P<0.001)
Tracheal
chain
of methanolic
extracts of
wood, bark,
fruit and leaf
Casuarina
equisetifolia
31-
32
Cordia myxa extract inhibited contraction in both
epithelium-intact and denuded sheep trachea rings
induced by acetylcholine. The scale of relaxation with
Cordia myxa extract was dose dependent and slightly
more potentin epithelium denuded rings than
epithelium-intact preparations. L-NAME (10 nM-100
uM) but not DNAME completely inhibited the relaxant
effect in a concentration dependent manner. Cordia
myxa extract -induced relaxation was inhibited by
methylene blue (1 -100 uM), and verapamil (100 nM),
and removal of extracellular Ca2+. In contrast, Cordia
myxa extract - induced relaxation was potentiated by L-
NOARG treatment.
Sheep
trachea.
Alcoholic
extract
Cordia myxa
33-
34
It caused relaxant, inhibitory effect on histamine (H1)
and muscarinic receptors, and stimulatory effect on β-
drenoceptor on guinea pig tracheal chains. The results
showed a preventive effect of the extract and its
constituent safranal on total and differential count of
WBC in blood of sensitized guinea pigs.
Guinea pig
tracheal
chains and
ovalbumin-
sensitized
guinea pigs
Hydroethanolic
extract of
stigma and
safranal
Crocus sativus
35-
36
Sixty seven percent inhibition of spasm in respiratory
smooth muscles were observed of Dolichos lablab
alcoholic fraction at 100 mg/kg body weight
Respiratory
smooth
muscles
Alcoholic
fraction
Dolichos
lablab
37-
39
The smooth muscle of the bronchial tree was relaxed by
ephedrine. Compared with epinephrine, the action of
ephedrine was slow in onset, complete an hour or more
after administration. Ephedrine also prevented
histamine-induced broncho-constriction in patients
with asthma.
Tracheae of
cats, dogs,
rabbits,
guinea-pigs,
and rats.
Clinical
Ephedrine
Ephedra
species
40-
41
Inhibited the tone of guinea-pig tracheal chain and rat
diaphragm).
Guinea -pig
tracheal
Aqueous
extract
Hibiscus
sabdariffa
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
205
chain and rat
diaphragm
42-
43
It produced antispasmodic effect mediated through a
combination of anticholinergic and Ca2+ antagonist
mechanisms.
Guinea -pig
trachea
The crude
extract of the
seeds
Hyoscyamus
niger
44-
45
Caused no effect on the trachea. Larger concentrations
(up to 3 mg/ml) caused nonsustained large
contractions of the trachea. The contractile effects were
not inhibited by atropine
Isolated
trachea
Low conc. of
petaline
chloride, a
quaternary
alkaloid from
Leontice
leontopetalum
Leontice
leontopetalum
46-
47
Inhibited carbachol (1 μM) and K+ (80mM) induced
contractions in Guinea pig tracheal ring strips, in a
pattern similar to that of dicyclomine. The crude extract
at 0.03 mg/ml produced a rightward parallel shift of
carbachol curves, followed by nonparallel shift at
higher concentration (0.1 mg/ml), suppressing
maximum response, similar to that caused by
dicyclomine.
Guinea - pig
tracheal ring
strips
Crude extract
Lepidium
sativum
48-
49
Measurements of specific airway resistance revealed
dose-dependent broncho-dilatory activity
Airways
smooth
muscle
reactivity in
guinea pigs
Polysaccharide
- polyphenolic
conjugate
isolated from
flowering parts
ofLythrum
salicaria
Lythrum
salicaria
50-
51
possessed relaxant effects on the guinea pig tracheal.
Guinea - pig
tracheal
The leaves oil
Melissa
officinalis
52-
53
Inhibited histamine-induced guinea pig tracheal chain
contractions non-competitively.
Guinea - pig
tracheal
chain
The ethanol:
acetone (1:1)
extract(0.5 ml
of 100 mg/ml)
Mirabilis
jalapa
54
Phenolic compounds (kuwanon U, moracin O and
albanol B) showed strong antispasmodic
Rat tracheal
smooth
muscles
Phenolic
compounds
Morus nigra
55
The crude methanol extract exhibited relaxant effect on
CCh- and K⁺ (80 mM)-induced contractions in isolated
rabbit tracheal preparations.
Rabbit
tracheal
preparations
Crude
methanol
extract
Myrtus
communis
56
Thymoquinone caused a concentration-dependent
decrease in the tension of the tracheal smooth muscle
pre-contracted by carbachol, when investigated in
Guinea pig isolated tracheal zig-zag preparation. It
totally abolished the pressor effects of histamine and
serotonin on the Guinea pig isolated tracheal smooth
muscles. These effects were suggested to be mediated,
at least in part, by inhibition of lipoxygenase products
of arachidonic acid metabolism and possibly by non-
selective blocking of the histamine and serotonin
receptors.
Guinea- pig
tracheal
smooth
muscle
Thymoquinone
Nigella sativa
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
206
Table 2 Medicinal plant affected gastrointestinal smooth muscle contractility
Ref
Action
Model
Extract or
compounds
Medicinal
plant
57
An increase of the spontaneous contraction of
rabbit-duodenum was established by garlic
solution. Blockade the M3 muscarinic receptors of
the smooth muscle by atropine sustained normal
contraction.
Rabbit
duodenum
Application (4
g/ml)
Allium
sativum
58
It caused reduction of intestinal contraction.
Neostigmine and pilocarpine effect was inhibited
by the administration of Ammi visnaga.
Rabbit jejunum
Boiled distilled
water seeds
extract
Ammi visnaga
17-
19
It showed spasmolytic activity and and
antihistaminic activity on guinea pig ileum.
Guinea -pig
ileum and rat
ileum
Alcoholic extract
of the aerial parts
Andrachne
aspera
59
The crude herbal extract induced an immediate,
moderate, and transient contraction of guinea pig
ileum via the activation of cholinergic neurons of
the gut wall.
Guinea-pig
ileum
Crude herbal
extract
Anthemis
nobelis
60-
61
It produced antispasmodic effects against
histamine, serotonine and acetylecholine
induced spasms.
Rats
A defatted
ethanolic extract
of the rhizomes
Arundo donax
62-
63
It caused relaxation of spontaneous contractions
of isolated smooth muscle of rabbit jejunum.
Smooth muscle
of rabbit
jejunum
Aqueous extract
Asparagus
officinalis
64-
66
They induced stimulatory effect which abolished
by atropine, indicated that the stimulatory effect
on smooth muscle was mediated by cholinergic
effect.
Duodenum and
ileum smooth
muscles in rats
Ethanol , n-
butanol, and ethyl
acetate extracts
Calotropis
procera
67
50-1000 mg/kg of dry latex produced a dose-
dependent decrease in intestinal transit along
with a decrease in intestinal content. At lower
doses dry latex produced dose-dependent
gastro-intestinal smooth muscles in vitro (rabbit
ileum and fundus of rat stomach) that was
followed by desensitization at higher doses.
Smooth
muscles of
gastro-
intestinal tract
in rats and
rabbits
Dry latex
68
Latex of Calotropis procera inhibited intestinal
motility and its action was potentiated by
atropine and loperamide.
On intestinal
transit in rats
using charcoal
meal test
Latex alone and
with loperamide
and atropine
69-
70
The plant induced stimulatory action unaffected
by atropine and diphenhydramine, but were
inhibited by papaverine.
Small intestine
in the guinea-
pig
Several extracts
Capsella
bursa-pastoris
71
The extract of dried or green plant causes strong
contraction of the small intestine of guinea pigs.
A quarternary ammonium salt has been isolated
from the herb which is reported to be responsible
for this activity.
Guinea pig
small intestine
Extract of dried
or green plant
72-
73
The maximal contractile responses of the treated
birds decreased significantly compared to those
of the control group. The decrease was also
In vivo and in
vitro, intestinal
and lung
Soaking seeds
extract
Cassia
occidentalis
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
207
directly related to the length of treatment. The
day 5 group showed the maximum decrease. The
in vitro study suggested involvement of smooth
muscles as a primary site for the toxicosis caused
by Cassia occidentalis. The decrease in maximal
response of lung parenchymal strip suggested
the existence of an active principle(s) in the
extract which caused the effect by systemic
absorption.
parenchimal
strips of
chickens
74-
75
The bark extract reduced contractions in isolated
ileum induced by spasmogens like ACh,
Histamine, KCl and BaCl and potentiated the
effect of Nifedipine suggesting an antimuscarinic,
antihistaminic and a calcium channel blocking
action.
Isolated ileum
Bark extract
Casuarina
equisetifolia
76-
77
The crude extract exhibited a dose-dependent
increase in relaxation of smooth muscles, starting
from 5 mg/ml and maximum effect was found at
20 mg/ml (92.86%). The ethyl acetate and
chloroform fractions of Chenopodium album
exhibited relaxation of the intestinal muscles
(43.48 and 51.52%, respectively); whereas, n-
butanol fraction of Chenopodium album produced
strong relaxant effect (91.18%).
Intestinal
smooth
muscles of
rabbit
The plant was
extracted in
ethanol and
fractionated in
ethyl acetate,
chloroform, n-
butanol and
water.
Chenopodium
album
78-
79
The extract produced the normal rhythmic
contraction of rabbit jejunum, which reversed by
prior addition of cyproheptadine. Methanolic
extract also produced a stimulant activity on rat
uterus which was blocked by cyproheptadin.
Rabbit jejunum
and rat uterus
Methanolic
extract
Clerodendrum
inerme
80
The isolated guinea-pig ileum evoked
contractions were decreased by aqueous and
ethanol extracts of Crocus sativus petals.
Guinea -pig
ileum
Petals ' aqueous
extract
Crocus sativus
81-
82
All the isolated compounds elicited a
concentration-dependent inhibition of the
spontaneous and electrically-induced
contractions of guinea-pig ileum. Sakuranetin
and the ent-labdane inhibited ileum contractions
evoked by acetylcholine, histamine, and barium
chloride.
Guinea -pig
ileum
Compounds
isolated from the
chloroform-
methanol (1:1)
extract
(sakuranetin , 6-
hydroxy
kaempferyl 3,7-
dimethyl ether,
hautrivaic acid,
and ent-15, 16-
epoxy-9 alpha H-
labda-13(16)14-
diene-3 beta, 8
alpha-diol)
Dodonaea
viscose
83-
86
Hexane extract, increased the tone of the guinea
pig ileum preparation and reduced the strength
of the contractions following field stimulation.
Guinea-pig
ileum
Several organic
extracts
Erodium
cicutarium
87
The extract antagonized the effect of
acetylcholine on the isolated guinea-pig ileum
preparation.
Guinea -pig
ileum
Alcoholic extract
Equisetum
arvense
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
208
88-
89
The aqueous-methanol extract predominately
more potent against CCh than isotonic high K+
solutions-induced contractions, similar to
dicyclomine, suggesting the presence of
anticholinergic and calcium channel blocking
[CCB] activities, which were confirmed when the
extract shifted the CCh and Ca2+ concentration-
response curves in rat ileum and trachea,
towards right. Among intestinal preparations
from various species, both anticholinergic and
CCB effects of the aqueous-methanol extract
were exhibited at lower concentrations in rat
than the other species. In tracheal preparations,
the extract was the most potent in its CCB effect
in rabbit.
Jejunum, ileum
and tracheal
preparations of
rat, guinea-pig
and rabbit
Aqueous -
methanol extract
Fumaria
parviflora
90-
91
The hydro-alcoholic extract of licorice had
modifying effect on colon motility via synergist
effect with beta adrenergic receptors and
independent of the alpha adrenergic receptors.
Rat colon
The hydro-
alcoholic extract
Glycyrrhiza
glabra
92-
93
It was a potent relaxant, inhibited the contraction
induced by various types of stimulants, such as
CCh, KCl, and BaCl2 with IC50 values of 4.96±1.97
microM, 4.03±1.34 microM and 3.70±0.58
microM
Several isolated
tissues
Isoliquiritigenin
isolated from an
aqueous extract
of licorice
94-
95
Alcoholic extract of licorice rhizome decreases
bowel motility. The contraction force exerted on
the isolated duodenum pieces by acetylcholine
was remarkably reduced in the presence of
licorice rhizome extract compared to that of the
control group (P<0.05).However, this response
in the presence of atropine, propranolol and N-w-
nitro- L arginine methyl ester (L-NAME) was not
changed significantly.
Rat duodenum
pieces
Alcoholic extract
of licorice
rhizome
96
a significant (p < 0.01) dose dependent relaxant
effect (IC50 = 350 μM) on rat ileal strip
comparable to the effect shown by nifedipin and
papaverine. The extract when administered ip., it
also significantly (p < 0.05–0.01) reduced the
intestinal transit (13-35%) in rats (IC50 = 250
μM)
In vivo in rats
and in vitro, rat
ileal strip
Methanol extracts
Hibiscus
sabdariffa
97-
98
Extracts inhibited the concentration curve
response to histamine, serotonin and
acetylcholine induced contractions.
Different GIT
tissues of rats
and guinea-pigs
Methanol and
dichloromethanol
extracts of the
leaves and stems
Juniperus
oxycedrus
42-
43
It produced antispasmodic effect mediated
through a combination of anticholinergic and
Ca2+ antagonist mechanisms.
Rabbit jejunum
and guinea-pig
ileum
The
crude extract
Hyoscyamus
niger
99-
100
Extract showed antispasmodic action on excised
rat ileum. When acetylcholine was given in
presence of methanolic leaves extract of Lantana
camara, extract caused marked decrease in
contraction of ileum, indicating blocking
cholinergic receptors.
Rat ileum
Methanolic leaves
extract
Lantana
camara
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
209
101
When the extracts at 125 and 250 mg/kg doses
were administered ip, it caused significant
reduction in fecal output compared with castor
oil treated mice. At higher doses (500 and 1000
mg/kg), the fecal output was almost completely
stopped.
Charcoal and
castor oil
models in mice
Lantana camara
leaf powder,
Lantana camara
methanolic
extract,
102
Caused contraction of the ileum, and no effect on
the trachea. Larger concentrations (up to 3
mg/ml) increased the amplitude of the phasic
contractions of the ileum. The contractile effects
were not inhibited by atropine.
Isolated iliem
Low
concentrations of
petaline chloride,
a quaternary
alkaloid from
Leontice
leontopetalum
Leontice
leontopetalum
103
Caused concentration-dependent relaxation of
guinea-pig isolated ileal longitudinal segments,
the effect was not blocked by propranolol (10-6
M) alone or in combination with prazosin (3 x 10-
8 M), or by indomethacin (10-6 M), but was
reduced by desensitization of the preparation by
prior exposure to a combination of propranolol
and yohimbine
Guinea -pig
isolated ileal
longitudinal
segments
Oblongine
chloride, a
quaternary
alkaloid from
Leontice
leontopetalum
104
caused a concentration dependent stimulatory
effects both in jejunum and ileum, which was
blocked by atropine. In rabbit jejunum, the
stimulant effect of aqueous- methanolic extract
remained unchanged in the presence of atropine,
pyrilamine or SB203186, while in rabbit ileum,
the stimulatory effect was partially blocked by
atropine.
Isolated gut
preparations of
mouse rabbits
and guinea-pig:
jejunum and
ileum
Aqueous
methanolic
extract of the
seeds
Lepidium
sativum
105
the extract (0.01-5 mg/ml) reversed carbachol (
1 μM) and K+ (80 mM)- inducedcontractions
with higher potency against carbachol.
Isolatedrat
ileum
Seed extract
106
crude extract completely inhibited carbachol,
low K+(25 mM) and high K⁺(80 mM)-induced
contractions, while in Guinea-pig tissues, crude
extract caused complete inhibition of only
carbachol induced contraction. In rabbit tissues,
crude extract completely inhibited carbachol and
low K+ -induced contractions sensitive to K+
channel antagonists. Pre-treatment of Guinea-pig
and rat tissues with crude extract caused a
rightward shift in carbachol- induced
contractions, while in rabbit and rat tissues,
crude extract shifted isoprenaline curves.
Isolated ileum
and jejunum of
many animals
Crude extract
107
The alcoholic extracts produced spasmogenic
effect on the isolated ileum
Guinea-pig
ileum
Alcoholic extracts
of whole Linum
usitatissimum
(0.1, 0.2, 0.4 and
0.8 ml)
Linum
usitatissimum
108
Flaxseed extract reduced the diarrheal score in
mice, by 39%, 63.90% and 68.34% at the
respective doses of 100, 300 and 500mg/kg.
Intestinal secretions were reduced by 24.12%,
28.09% and 38.80%, and intestinal motility was
reduced by 31.66%, 46.98% and 56.20% at
Mice in vivo and
isolated rabbit
jejunum
preparations
Flaxseed extract
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
210
respective doses of 100, 300 and 500mg/kg.
Flaxseed extract produced a dose-dependent
inhibition of both spontaneous and high K+
(80mM)-induced contractions, and shifted the
concentration-response curves of Ca++ to the
right with suppression of the maximum
response.
109
The hexane, chloroform, ethyl acetate and 50%
ethanol in water extracts (10 μl/5 ml organ bath)
produced contractile effects. The largest
contractions were elicited by the 50% ethanol in
water extract.
Isolated guinea
pig ileum
The effects of
hexane,
chloroform, ethyl
acetate, and 50%
ethanol in water
extracts of
Lythrum salicaria
Lythrum
salicaria
110
The results showed that Lythrum salicaria
extracts possessed moderate muscarinic
receptor agonistic effect in Guinea pig ileum. The
most prominent response was triggered by the
50% ethanol in water extract in a concentration-
dependent manner. Atropine, indomethacin and
PPADS plus suramin significantly reduced the
contractile response caused by this extract.
Guinea- pig
ileum
The n-hexane,
chloroform, ethyl
acetate and 50%
ethanol in water
extracts of the
air-dried
flowering parts of
Lythrum salicaria
111-
112
The extract showed a potent relaxnat activity on
isolated rabbit jejunum that was refractory to the
adrenergic blockers propranolol and tolazoline.
Prior adminstration of the extract,
physiologically blocked the stimulant effect of
histamine on rat fundus strip.
Rabbitjejeinum
and rat fundus
strip
Methanolic
extract of the fruit
seeds
Mangifera
indica
113-
114
The extract possessed a significant
antispasmodic activity, it inhibited the action of
acetylcholine, bradykinin, prostaglandin E2,
histamine and oxytocin, with putative selectivity
for cholinergic contractions
Several smooth
muscle
preparations
Hydroalcoholic
extract of the
roots and aerial
parts
Marrubium
vulgare
115
The extract caused dose-dependent (0.3-3
mg/ml) relaxation of spontaneous and low K+ (25
mM)- induced contractions of the isolated rabbit
jejunum, while it exhibited weak inhibitory effect
on high K+ (80mM). The inhibitory effect of the
extract on low K+- induced contractions was
partially inhibited in the presence of
glibenclamide, while completely blocked by 4-
aminopyridine.
Isolated rabbit
jejunum
Crude aqueous-
methanolic
extract
Matricaria
chamomilla
116
possessed relaxant effects on the guinea pig ileal
smooth muscle
Ileal smooth
muscle
The leaves oil
Melissa
officinalis
117
Inhibited the rat ileum response to KCl, ACh and
5-HT in a concentration dependent manner.
Rat ileum
response
The essential oils
and citral
118
The extract possessed site- and dose-dependent
effects on the contractile activity of the
gastrointestinal tract, the motility response being
impacted in the jejunum and ileum but not in the
antrum and colon
Different
segments of the
gastrointestinal
tract of mice
Hydroethanolic
leaf extract
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
211
119
The crude extract caused inhibition of
spontaneous and high K+ induced contractions,
with EC50 values of 1.80 (1.34–2.24) and 0.60
mg/ml (0.37–0.85), respectively. The results
suggested spasmolytic activity, mediated
through calcium channel blockade which further
confirmed that the extract caused a rightward
shift in the Ca++ concentration- response curves,
similar to verapamil.
Isolated rabbit
jejunum
preparations
Crude extract
Mentha
longifolia
.
120
The results showed that KCl-, carbachol and
BaCl2- induced ileal contractions were inhibited
(P<0.001) by cumulative concentrations of the
extract with the same potency. The extract (0.25-
1 mg/ml) inhibited (P<0.01) ileal contractions
induced by CaCl2 (0.45-2.7 mM) in a
concentration- related manner. The
antispasmodic effect of the extract was not
affected by propranolol, N omega-nitro-L-
arginine methyl ester and naloxone.
Rats ileal
preparation
Leaf
hydroalcoholic
extract
121
The extract exhibited an inhibitory effect (IC50
18±0.7 micorg/ml) on gut smooth muscle
contractility.
Gut smooth
muscle
The extract of the
flowers (1-1000
mug/ml)
Mirabilis
jalapa
122
Phenolic compounds (kuwanon U, moracin O and
albanol B) showed strong antispasmodic effects
on isolated rat ileum
isolated rat
ileum
Phenolic
compounds
Morus nigra
123
The extract and its chloroform fraction inhibited
carbachol- induced contractions of rabbit
jejunum more potently than high K+ (80 mm). In
Guinea-pig ileum, the extract and its aqueous and
ethyl acetate fractions, exhibited
atropine-sensitive gut stimulant activity
Rabbit jejunum,
guinea-pig
ileum
Crude extract
124
The crude methanol extract caused complete
relaxation of spontaneous and K⁺(80 mM)-
induced contractions in isolated rabbit jejunum.
It caused right ward parallel shift of calcium
concentration response curves.
Isolated rabbit
jejunum
Crude methanol
extract
Myrtus
communis
125-
126
The extract potentiated both spontaneous and
electrically evoked contractions of guinea pig
ileum, this effect was not antagonized by the
adrenergic blocker (tolazoline).
Guinea pig
ileum
Crude extract
Nerium
oleander
127
The extract exerted mild to moderate dose
dependent relaxant effects of the ileum, and its
spasmolytic activity was mediated through
calcium antagonist effect.
Guinea pig
ileum
Aqueous extract
of the seed
Nigella sativa
128
Inhibited spontaneous movements of rabbit
jejunum. The calcium channel blockade was
suggested as spasmolytic mechanism.
Rabbit jejunum
Volatile oil and
ethanol extract
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212
Table 3 Medicinal plant affected vascular smooth muscle contractility
Ref
Action
Model
Extract or
compounds
Medicinal
plant
129-
136
Garlic-derived polysulfides stimulate the
production of the vascular transmitter and
enhance the regulation of endothelial nitric oxide
(NO), which induce smooth muscle cell relaxation,
vaso-dilation, and BP reduction. Garlic induced
significant reduction in systolic and diastolic
blood pressure due to a direct relaxant effect on
smooth muscles.
Experimental
and clinical
studies
Raw garlic,
several extracts
and polysulfides
Allium
sativum
137-
139
It was selectively inhibited the contractile
response in the rat isolated aortic ring and portal
vein segment. It caused nonspecific inhibition of
vascular smooth muscle.
Rat aortic ring
and portal
vein segment
Visnadine
Ammi visnaga
140
Visnadin, 60.0 μg/ml or 120.0 μg/ml, increased
coronary blood flow in isolated guinea-pig hearts
by 46% and 57% respectively
In isolated
guinea-pig
hearts
Visnadine
141
Khellin, visnagin or crude mixture of the Ammi
visnaga active principles have a direct muscle
relaxant. Oral preparation is used to dilate the
coronary arteries efficiently in angina pectoris
Clinical
Khellin, visnagin
or crude mixture
of the Ammi
visnaga
61,
142
It possessed vasopressor activity, raising the
blood pressure in dogs after small doses and
causing a fall in larger doses.
In dogs
Alkaloid gramine
extracted from
the plant
Arundo donax
60-
61
It produced hypotensive effect
Rats
A defatted
ethanolic extract
of the rhizomes
143-
144
Adding of Capparis spinosa aqueous extract
(CSAE)during the plateau phase of contraction,
induced by noradrenaline and KCl, produced a
rapid relaxation. Incubation of aortic ring with
CSAE during 30 min shifted the noradrenaline
induced dose response curve (p<0.001), the
maximum response (p<0.001) was attenuated
which indicating that antagonistic effect of the α1-
adrenoreceptors was non-competitive.
Aortic rings of
rats
Aqueous extract
Capparis
spinosa
145
Addition of extracts during the stage of
contraction led by the phenylephrin for the
thoracic arteries showed a light vasodilatation.
Incubation (30 min) with extracts showed a
significant vasodilator effect for fruits and kernels,
and vasoconstrictor effect for leaves.
Thoracic aorta
rings and
windpipe of
rat
Aqueous extract
of different parts
(roots, leaves,
stems, flowers,
fruits and
kernels)
146
The extract inhibited contraction elicited by
noradrenaline (NA) and potassium chloride (KCI).
It also relaxed aortic rings pre-contracted with 10-
7 M NA and 50m M KCI. The relaxation did not
require the presence of an intact vascular
endothelium and was not affected by
indomethacin and methylene blue.
Rat aortic
rings
Aqueous extract
of the leaf
Cassia
occidentalis
147-
148
This compound did not affect contraction induced
by a high concentration of potassium (60 mM K+),
Rat aorta
strips
A diester
composed of
Cichorium
intybus
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
213
while it inhibited NE-induced vaso-contraction in
the presence of nicardipine. The inhibition of
vaso-contraction is due to a decrease in calcium
influx from the extracellular space, which
enhanced by NE.
(S,S)-tartaric acid
and caffeic acid
isolated from the
plant
149
Echinacoside mediates the endothelium-
dependent vasodilator action in rat thoracic aortic
rings through nitric oxide (NO)-cGMP pathway.
Rat thoracic
aortic rings
Echinacoside , a
phenylethanoid
glycoside isolated
from Cistanche
tubulosa
Cistanche
tubulosa
150-
151
It showed inhibitory effect on contractions
induced by noradrenaline in isolated rat aortic
strips. Kankanoside F, kankanose, echinacoside,
acteoside, and cistanoside F, which isolated from
the extract were responsible for thevasorelaxant
activity.
Rat aortic
strips
Methanolic
extract from the
dried stems
152-
153
The extract possessed anti-hypertensive activity
by cardio-depression and vaso-relaxation. It
evoked vaso-relaxant effects which totally
abolished by removal of the endothelium layer or
by a pre-treatment with L-NAME
In vivo, rabbits
and in vitro rat
aortic strips
Aqueous extract
Citrus
aurantifolia
154-
156
It appeared that calcium-dependent K channels
(BKCa) has a partial role in the relaxing effect of
the ethanolic extract, but not aqueous extract.
However, with the using of high K+ Krebs, both
extracts exhibited relaxant effect due to reducing
the entry of calcium ions from outside. The
adrenergic receptor α1 has a role but with
different magnitude between the extracts, with
high degree for aqueous extract, that reduced the
maximum response (Emax) of aortic rings to
phenylephrine, and this was similar to the effect of
α1-blocker (prazosin).
Rabbit aortic
rings
Ethanolic and
aqueous extracts
Convolvulus
arvensis
157
It caused hypotensive effect and respiratory
stimulant effect. The hypotensive effect was due
to activation of parasympathetic ganglia and
dilatation of peripheral blood vessels, whereas the
respiratory stimulant effect was due to activation
of chemoreceptors in the aortic arch and carotid
body.
In vivo, rabbit
Fruit mucilage at
different stages of
maturity
Cordia myxa
158-
159
It showed slow relaxation activity against
norepinephrine (NE)-induced contraction of rat
aorta with/without endothelium. This compound
did not affect contraction induced by a high
concentration of potassium (60 mM K+), while it
inhibited NE-induced vaso-contraction in the
presence of nicardipine.
Rataorta
strips
Dicaffeoyl -meso-
tartaric acid from
Equisetum
arvense
Equisetum
arvense
160
The crude extract induced mainly endothelium-
dependent relaxant effects via NOS activation
Rat thoracic
aorta
Extract of dried
and powdered
calyces
Hibiscus
sabdariffa
161
Caused relaxation of the epinephrine-contracted
aorta. Larger concentrations (up to 3 mg/ml)
caused nonsustained large contractions of the
Isolated aorta
Low conc. of
petaline chloride,
a quaternary
alkaloid from
Leontice
leontopetalum
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
214
aorta. The contractile effects were not inhibited by
atropine
Leontice
leontopetalum
162
Caused concentration-dependent relaxation of
epinephrine-pre-contracted guinea-pig isolated
main pulmonary artery rings. The effect was not
affected by propranolol or by indomethacin but
was significantly attenuated by pre-treatment
with 3 x 10-5 M ATP and potentiated by
pretreatment with quinacrine(10-5 M).
Guinea -pig
isolated main
pulmonary
artery rings
Oblongine
chloride (3 x 105-
10-3 M), a
quaternary
alkaloid from
Leontice
leontopetalum
163
The extract strongly inhibited the in vitro KCl-
induced contraction of rat aorta. Furanic labdane
diterpenes, marrubenol and marrubiin were the
most active compounds.
Rat aorta
The crude
extracts of the
aerial parts
Marrubium
vulgare
164
The extract inhibited the contractile responses of
rat aorta to noradrenaline and to KCl (100 mM).
Inhibition was greater in aorta from
spontaneously hypertensive rats compared to
normotensive rats and was not affected by the NO
synthase inhibitor.
Rat aorta
Crude extract
165
Marrubenol inhibited the contraction of rat aorta
evoked by 100 mM KCl (IC50: 11.8±0.3 microM,
maximum relaxation: 93±0.6%) than of the
contraction evoked by noradrenaline (maximum
relaxation: 30±1.5%) in rat aorta. It also
simultaneously inhibited the Ca2+ signal and the
contraction evoked by 100 mM KCl, and decreased
the quenching rate of fura-2 fluorescence by Mn2+.
rat aorta
Marrubenol (a
diterpenoid
extracted from
Marrubium
vulgare)
166-
167
The extract caused hypotensive and vaso-dilating
actions due to the vascular smooth muscle
relaxation in rabbits.
Rabbit , in vivo
Crude extract
Melilotus
officinalis
168
The extract and rosmarinic acid isolated from the
extract possessed vasorelaxant effect, entirely
dependent on the presence of endothelium and
was abolished by pretreatment with L-NAME,
while pretreatment with indomethacin and
glibenclamide reduced the relaxation to a minor
extent
Isolated rat
aortic rings
precontracted
with
phenylephrine
Aqueous extract
Melissa
officinalis
169
In rat aortic rings, the crude extract and aqueous
fraction-induced endothelium-dependent
atropine-sensitive vasodilator effect. In rabbit
aortic rings, crude extract relaxed phenylephrine
(1 μM) and high K+ (80 mM) pre-treated ring.
Chloroform fraction was more potent against high
K+, similar to verapamil and caused a rightward
shift in the Ca++ concentration response curves.
Aqueous fraction partially relaxed high K+
pretreated ring.
Rat and rabbit
aortic rings
Crude extract and
fractions
Mentha
longifolia
170
The extract possessed dual vasoactive effects, and
the relaxation was greater than the contraction.
The relaxation was mediated by inhibition of
voltage- and receptor-dependent Ca2+ channels
in vascular smooth muscle cells, while the
contraction occurred via activation of ryanodine
receptors in the sarcoplasmic reticulum.
Isolated rat
thoracic rings
Leaves extract
Morus alba
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215
171
The crude methanol extract caused relaxation of
phenylephrine (1 μM)- and K⁺(80 mM)-induced
contractions in isolated rabbit aorta preparations,
similar to verapamil.
Isolated rabbit
aorta
preparations
Crude methanol
extract
Myrtus
communis
172
Incubation with the aqueous seed extract during
30 min caused a right shift of the contraction
response curve of aortic ring to norepinephrine
with a reduction of the maximal contraction
response (P<0.01). Endothelium destruction
significantly reduced the vaso-relaxant effect of
the extract at a dose of 30 mg/ml (P<0.01).
Rat aortic ring
Aqueous seed
extract
Nigella sativa
173
The maximum contraction of aortic ring
preparations in response to phenylephrine (10-6
m) was significantly decreased in hypertensive
rats fed with olive oil. The relaxant responses to
acetylcholine (10-5m) were significantly enhanced
in the rings from hypertensive rats treated with
olive oil. Olive oil attenuated the dose-response
curves induced by phenylephrine (10-8-10-5 m)
from hypertensive rats, accompanied with a
slower contraction.
Rat aortic ring
preparation
Oliv e oil
Olea europaea
174-
175
The crude extract caused concentration-
dependent relaxation of both phenylephrine and
high K+ (80mM)- induced contractions and caused
a rightward shift of the calcium concentration–
response curves similar to the effect of verapamil.
Isolated rabbit
aorta
Crude extract
Orchis
mascula
Table 4 Medicinal plant affected uterine smooth muscle contractility
Ref
Action
Model
Extract or
compounds
Medicinal
plant
61,
142
It produced hypotensive and antispasmodic effects
against histamine, serotonine and acetylecholine
induced spasms. Bufotenidine showed three main
pharmacological actions, anti-acetylecholine effect,
histamine release and uterine stimulant effects.
Rats
A defatted
ethanolic
extract of the
rhizomes
Arundo
donax
61-
142
Bufotenidine showed three main pharmacological
actions, anti-acetylecholine effect, histamine release
and uterine stimulant effects.
Rats
Bufotenidine
176
It exerted contractile activity on the rat uterus which
was similar to that of oxytocin. The effective
substance had some characteristics of a polypeptide.
Rat uterus
A purified
substance from
an alcohol
extract
Capsella
bursa-
pastoris
177
Water extracts (infusions) from a group of medicinal
plants including Capsella bursa-pastoris enhanced the
uterine tonus in isolated rabbit and guinea pig uterine
horn.
Isolated rabbit
and guinea pig
uterine horn
Aqueous
extract
178
The plant was used in the treatment of menorrhagia
and metrorrhagia, which seem to be mediated
through an increased contraction of smooth muscles
and uteromimitic effect. As a tea-like infusion, the
Clinical
Tea infusion
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
216
recommended dose is 2 g to 4 g in 150 ml of water
after boiling for 15 minutes.
179-
180
The leaf extract and scopolamine showed
antispasmodic effects, while root extract and
acetylcholine caused contraction of the isolated rat
uterus and rectum whole muscle. The results
indicated that the plant contained antispasmodic and
spasmogenic constituents.
Rat uterus and
rectum smooth
muscles
Leaf and root
extracts
Daturametel
181-
182
The tertiary base possessed papaverine like
nonspecific smooth muscle relaxant and spasmolytic
activity, but its activity was found to be about one-
tenth of that of papaverine.
Ileum, uterus,
blood vessels and
trachea of
different species
of animals
Anitrogen
containing
tertiary base
isolated from
the seeds
Daucus
carota
83-
86
All extracts had a spasmogenic action on isolated
uterus preparation of the rat. The methanol extract
produced regular monophasic contractions of the
quiescent uterus, which ceased immediately when the
tissue was washed.
Rat uterus
Several organic
extracts
Erodium
cicutarium
41
extracts induced rat bladder and uterine contractility
in a dose-dependent manner via a mechanism
unrelated to local or remote autonomic receptors or
calcium channels
Rat bladder and
uterus
Aqueous
extract
Hibiscus
sabdariffa
41
inhibited the tone rhythmically contracting rat uterus
Rat uterus
Aqueous
extract
183
the extract increased rat uterine motility.
Isolated rat
uterus
Aqueous
extracts of
Luffa cylindrica
leaves
Luffa
cylindrical
184
It inhibited the spontaneaous activity of the uterine
muscle and effectively antagonised the stimulant
activity of acetylcholine on the muscle.
Isolated uterus
Methanolic
extract of
Mangifera
indica fruit
seeds
Mangifera
indica
185
The extract significantly decreased the strength,
frequency and contractile activity of uterine smooth
muscle, but the contractile activity was returned to
the basal level at the concentrations of 200 and 2000
μg/ml. The effects might not be through cholinergic
muscarinic receptors and atropine could enhance the
effects of the extract on frequency through other
receptors
Virgin rat Uterine
smooth muscle
Aqueous
extract of
Mango kernel
70
The extract of dried or green plant causes strong
contraction of uterus of guinea pig. A quarternary
ammonium salt has been isolated from the herb which
is reported to be responsible for this activity.
Guinea - pig
uterus
Extract of dried
or green plant
Capsella
bursa-
pastoris
186-
189
The seeds induced abortions in rats and mice, and the
root possessed uterine stimulatory effects.
In vivo,
mice and rats
The seeds of
the plant
Momordica
charantia
GSC Biological and Pharmaceutical Sciences, 2022, 19(01), 202–225
217
2. Conclusion
The World Health Organization (WHO) estimates that 4 billion people, 80 percent of the world population, presently
use herbal medicine for some aspect of primary health care. We still need herbal medicines to relax the uterine muscles
in cases of abortion, or to increase uterine contractions to enhance delivery. Spasmolytic drugs are required to relieve
gastrointestinal colic, while drugs which relax bronchial smooth muscles are needed in asthmatic attacks. This review
was designed to discuss the plants which possessed biological activity on smooth muscles to encourage the research in
this direction to introduce new drugs characterized by therapeutic efficacy and safety.
Compliance with ethical standards
Acknowledgments
The author like to acknowledge the College of Medicine, University of Thi-Qar for support.
Disclosure of conflict of interest
The author confirms that there is no conflict of interest.
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