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REVIEW
Scientific evaluation of medicinal plants used for the treatment
of abnormal uterine bleeding by Avicenna
Masumeh Mobli •Marzieh Qaraaty •
Gholamreza Amin •Ismaeil Haririan •
Mannan Hajimahmoodi •Roja Rahimi
Received: 9 September 2014 / Accepted: 19 January 2015 / Published online: 31 January 2015
ÓSpringer-Verlag Berlin Heidelberg 2015
Abstract
Purpose Abnormal uterine bleeding (AUB) is one of the
prevalent gynecological disorders that cause considerable
morbidity and management of that plays an important role
in protecting women’s health. This review focuses on
medicinal plants mentioned by Avicenna, a great Iranian
philosopher and physician (A.D. 980–1037), in his book
Canon for treatment of AUB.
Methods Medicinal plants mentioned in Canon for treat-
ment of AUB were elicited and searched in electronic
databases including PubMed, Scopus, Google Scholar and
Cochrane library to find studies that confirmed their effi-
cacy. Data were collected for the years 1980–2014.
Results The findings included 23 plants belonging to 18
families. Scientific findings have revealed that these plants
control AUB through four mechanisms of action including
inhibition of inflammatory process, inhibition of prosta-
glandins production, antiproliferative activity on human
cervical cancer cells (HeLa), and estrogenic activity. All of
the plants exhibited anti-inflammatory activity in vitro and/
or in vivo. Cuscuta chinensis and Portulaca olera-
cea exhibited estrogenic activity. Boswellia carteri,Lens
culinaris,Myrtus communis,Polygonum aviculare,Pista-
cia lentiscus, and Punica granatum have revealed inhibi-
tory activity on biosynthesis of prostaglandins. Some of the
mentioned plants including: Ceratonia siliqua,Cuscuta
chinensis,Cuscuta epithymum,Cydonia oblonga,Paeonia
sp., Portulaca oleracea,Solanum nigrum,Rumex aceto-
sa and Onopordum acanthium have shown antiprolifera-
tive activity on HeLa cells.
Conclusion Investigation of traditional Iranian medicine
literatures can lead to the identification of effective natural
medicines for the management of AUB; however, con-
clusive confirmation of the efficacy and safety of these
treatments needs more evaluations.
Keywords Abnormal uterine bleeding Avicenna
Medicinal plants Prostaglandin Estrogenic
Antiproliferative Anti-inflammatory
Introduction
Abnormal uterine bleeding (AUB) is an important men-
strual disorder covering 20 % of gynecological visits and
creates considerable morbidity in women of reproductive
age and imposes major medical, social, and economic
problems to women, their families, the workplace, and
health services [1–4]. The prevalence of AUB is estimated
at 11–13 % in general population and increases with age,
reaching 24 % in those aged 36–40 years [5]. Chronic and
M. Mobli G. Amin M. Hajimahmoodi R. Rahimi (&)
Department of Traditional Pharmacy, School of Traditional
Medicine, Tehran University of Medical Sciences,
1417653761 Tehran, Iran
e-mail: rojarahimi@gmail.com
M. Qaraaty
Traditional Medicine Clinical Trial Research Center,
Shahed University, Tehran, Iran
G. Amin
Department of Pharmacognosy, Faculty of Pharmacy, Tehran
University of Medical Sciences, Tehran, Iran
I. Haririan
Department of Pharmaceutics, Faculty of Pharmacy, Tehran
University of Medical Sciences, Tehran, Iran
M. Hajimahmoodi
Department of Drug and Food Control, Faculty of Pharmacy,
Tehran University of Medical Sciences, Tehran, Iran
123
Arch Gynecol Obstet (2015) 292:21–35
DOI 10.1007/s00404-015-3629-x
acute AUB and inter-menstrual bleeding are types of AUB
[6,7]. AUB has structural (organic) and non-structural
(non-organic) causes. Polyp, adenomyosis, leiomyoma,
malignancy and hyperplasia are structural causes. Coagu-
lopathy, ovulatory disorders, endometrial disorders, iatro-
genic causes and imbalance in the metabolism of local
endometrial prostaglandins are non-structural causes [3,8,
9]. Medical therapy is first-line treatment. However, cer-
tain situations may call for surgical management. Hor-
monal drugs such as IV conjugated equine estrogen,
combined oral contraceptives, and oral progestins are
considered as the first-line pharmacological treatments in
the management of AUB. However, increased risk of
myocardial infarction, stroke, invasive breast cancer, pul-
monary emboli and deep vein thrombosis in postmeno-
pausal women during treatment with these medications has
been reported [5,7]. Because of these serious side effects,
it seems logical to investigate other available sources to
discover more effective and safe drugs. One of the most
valuable ones to achieve this goal is traditionally used
remedies. One of the advantages of traditionally used
remedies is their use by people of a region for many years
and this issue may confirm their efficacy and safety.
Avicenna (A.D. 980–1037), a famous Iranian philosopher
and physician, has described AUB by terms such as ‘‘Efrat-e
Tams’’ or ‘‘Kesrat-e Tams’’ and also emphasized on its
etiology and treatment. In treatment section, he has implied
various herbs that could be used for the management of AUB
[10–12]. The aim of present study is to review medicinal
herbs claimed to be effective in ‘‘Canon of Medicine’’ for
AUB to new source that may be used as complementary and/
or alternative to conventional treatment.
Methods
Medicinal herbs used for the treatment of AUB were
extracted from ‘‘Canon of Medicine’’ (Table 1)[12].
Electronic databases including PubMed, Scopus, Google
Scholar and Cochrane library were explored for each of
these herbs and all retrieved articles were evaluated to
achieve any in vitro, animal, or clinical evidence for their
efficacy and pharmacological mechanisms related to AUB.
Studies either demonstrate direct efficacy of these medic-
inal herbs or effect of them in mechanisms involved in
AUB was considered. Data were collected for the years
1980 to June 2014. The search terms were ‘‘uterine
bleeding’’ or ‘‘menstrual cycle’’ or ‘‘menstruation’’ in title
and abstract and the name of each herb in the whole text.
Results from primary search were screened by two inde-
pendent investigators. References of finally included arti-
cles were reviewed for more relevant studies. Included
articles were reviewed to extract plant’s scientific name,
medicinal part and active components (if mentioned), and
animal model and species for in vivo studies. In human
studies, study design, number of patients, interventions,
duration of treatment and efficacy and tolerability of the
herbal treatment were also collected. Results are shown in
Tables 2,3and 4.
Findings and results
Below, the medicinal herbs mentioned for the management
of AUB in ‘‘Canon of Medicine’’ and all evidence con-
firming their efficacy are described individually.
Boswellia species
Oleogum resin from various Boswellia species has been
claimed to be effective for the management of AUB in
Table 1 Medicinal plants used for treatment of AUB mentioned in
‘‘Canon of Medicine’’
Scientific names Family Name(s) in ‘‘Canon of
Medicine’’ book
Boswellia sacra Flueck. Burseraceae Kondur
Ceratonia siliqua L. Fabaceae Kharnub
Cuscutachinensis Lam. Convolvulaceae Kashus
Cydonia oblonga Mill. Rosaceae Safarjal
Cymbopogon
schoenanthus (L.)
Spreng.
Poaceae Izkher
Hyoscyamus sp. Solanaceae Banj
Juglansregia L. Juglandaceae Juz
Lens culinaris Medik. Fabaceae Adas
Myrtus communis L. Myrtaceae Aas
Nymphaea alba L. Nymphaeaceae Nilufar
Oleae uropaeaL. Oleaceae Zeitun
Onopordum acanthium
L.
Asteraceae Shukaei
Paeonia officinalisL.
Paeonia emodi Wall. ex
Royle
Paeoniaceae Ood-al- Saleeb, Favania
Pistacia lentiscus L. Anacardiaceae Mastaki
Polygonum aviculare L. Polygonaceae Asi-al-raei
Portulaca oleracea L. Portulacaceae Boghla-al-homgha
Punica granatum L. Lythraceae Jolnar
Rhus coriaria L. Anacardiaceae Somagh
Rumex acetosa L. Polygonaceae Hommaz
Solanum nigrum L. Solanaceae Enab-al-saalab
Symphytum sp. Boraginaceae Samghuton
Tragopogon sp. Asteraceae Lahyat-al-tis
Ziziphus spina-christi
(L.) Willd.
Rhamnaceae Sedr
22 Arch Gynecol Obstet (2015) 292:21–35
123
Table 2 In vitro studies on plants used for treatment of AUB mentioned in ‘‘Canon of Medicine’’
Plant Part/extract Active constituent Result Reference
Boswellia carteri
Birdw.
Gum resin C(28)-hydroxylated
lupeolic acid
Suppression of eicosanoids biosynthesis through
inhibition of cytosolic phospholipase A2
[15]
Ceratonia siliqua
L.
Pods/crude polyphenol
fraction
Polyphenols Antioxidant activity [16]
Sapwood/methanol extract Gentisic acid and (-)-
epicatechin
Antitumor activity; ;intracellular ROS production
by HeLa cells after treatment with H2O2
[21]
Leaves/methanol extract Gallic acid, (?)-catechin
and quercetin
Cytotoxic effects and apoptosis induction on human
cancer cell line
[22]
Cuscuta chinensis
Lam.
Aerial parts/chloroform
and hydroalcoholic
extracts
–;Viability of Hela and MDA-MB-468 cells [26]
Seeds/ethanol extract Kaempferol and
isorhamnetin
Estrogenic activity [30]
Cuscuta epithymum
L.
Aerial parts/chloroform
and hydroalcoholic
extracts
–;Viability of Hela, HT-29 and MDA-MB-468 cells
by chloroform extract; ;viability of MDA-MB-
468 cells by hydroalcoholic extract
[26]
Cydonia oblonga
Miller.
Peel/polyphenolic extract – Inhibition of LPS-mediated activation of three
major cellular proinflammatory effectors, NF-jB,
p38MAPK and Akt
[31]
Lipophilic wax extract and
aqueous fermented
extract
– Antioxidant properties and cytotoxic effects on
human HeLa cell lines
[32]
Cymbopogon
citratus Stapf.
Leaves Polyphenols iNOS expression [34]
Leaves Chlorogenic acid Inhibition of proteasome and NF-jB pathway [35]
Leaves/aqueous extract – Inhibition of iNOS expression, NO production and
various LPS-induced pathways; Inhibition of LPS-
induced PGE
2
production
[36]
Leaves/phenolic acid-rich
fraction
Polyphenols Inhibition of LPS-induced PGE
2
production [36]
Cymbopogon
martinii (Roxb.)
Wats.
Essential oils – ;TNF-c, IL-1b, and IL-8 secretion levels of THP-1
cells
[38]
Juglansregia L. Bark/aqueous, chloroform
and alcoholic extracts
– Anti-inflammatory activity [44]
Lens culinaris
Medik.
Seed/methanol extracts – Inhibition of COX-2 [48]
Myrtus communis
L.
Leaves Myrtucommulone Suppression of typical proinflammatory cellular
responses
[102]
Leaves Myrtucommulone Inhibition of microsomal PGE
2
synthase-1 [103]
Nymphaea alba L. Rhizome/ethanol extract Alkaloids, tannins,
glycosides and
flavonoids
Antioxidant activities [54]
Onopordum
acanthium L.
Flower, fruit and leaves – Antiproliferative activity against Hela and MCF7
cell line
[60]
Onopordum
Macracanthum
Schousboe.
Aerial parts – Inhibition of TNFaand NO synthesis, as well as
VCAM1 surface expression
[61]
Onopordum
cynarocephalum
Boiss. and
C.I.Blanche.
Aerial part/aqueous extract – Inhibition of fetal bovine serum derived gelatinase
A and B; ;expression of endotoxin-induced
inflammation markers IL-6 protein and mRNA, as
well as gelatinase A and B -activity via NF-jB.
suppressed mRNA and protein levels of b-casein
[62]
Arch Gynecol Obstet (2015) 292:21–35 23
123
‘‘Canon of Medicine’’. B. carteri dried gum resin water
extract showed significant anti-inflammatory and analgesic
activities and also exhibited remarkable inhibitory activity
on production of Prostaglandin (PG) E
2
[13,14]. Triterpene
acids isolated from B. carteri resin exhibited marked anti-
inflammatory activity in inflammation in mice [14]. C(28)-
hydroxylated lupeolic acid from the gum resin of B. carteri
suppressed eicosanoid biosynthesis in intact cells [15].
Ceratonia siliqua L.
Ceratonia siliqua, commonly known as carob, is a plant of
the Mediterranean regions. The crude extract of the plant
pod exhibited antioxidant properties higher than certain
known polyphenols such as catechin, quercetin and gallic
acid alone [16,17]. This antioxidant activity may be
related to the presence of carotenoids and phenolic
Table 2 continued
Plant Part/extract Active constituent Result Reference
Paeonia
suffruticosa
Sndr.
Aerial part/aqueous extract Polyphenols, flavonoids
and trace metal
Inhibition of NO and TNF-aproduction [64]
Aerial part/aqueous and
ethanol extracts
Polyphenols, flavonoids
and trace metal
Antioxidant activity [64]
Root/hydroalcoholic
extract
Paeonol Regulation of TNF-a, IL-1b, IL-6, and IL-10
production
[65]
Paeonia species Root Paeoniflorin Induction of apoptosis of HeLa cells [66,67]
Pistacia lentiscus
L.
Resin – Inhibition of NO and PGE2 production [69]
Polygonum
aviculare L.
Aerial part – Inhibition of PGs biosynthesis and platelet
activating factor and induction of exocytosis
[71]
Aerial part Flavonol glucuronides Inhibition of ROS production
Portulaca oleracea
L.
Aerial part Polysaccharides Inhibition of cervical cancer cell growth [76]
Punicagranatum L. Leaves/methanol extract Phenols, flavonoids,
tannins and
anthocyanins
Antioxidant activity; cytotoxic activity [78]
Leaves/ethanol extract Phenols, flavonoids,
tannins and
anthocyanins
Inhibition of 5-lipoxygenase, AChE and BuChE [78]
Leaves/ethanol and
methanol extracts
Phenols, flavonoids,
tannins and
anthocyanins
Anti-inflammatory activity [78]
Flower/80 % ethanol
extract
Phenols, flavonoids,
tannins and
anthocyanins
Antioxidant, anti-inflammatory and antiproliferative
activities
[79]
Peel Punicalagin, punicalin,
strictinin A, and
granatin B
Inhibition of NO production and iNOS expression;
COX-2 and PGE2 inhibitory effect
[84]
Leaves/methanol and
ethanol extracts
– Anti-inflammatory activity [85]
Fruit Polyphenols Inhibition of COX2 activity and PGE
2
production [86]
Leaves 2-Methyl-pyran-4-one-3-
O-b-D-glucopyranoside
Blockage of both the TNFa-induced translocation
and activation of NF-jB
[87]
Rumex acetosa L. Aerial parts – Antiproliferative activity against Hela and MCF7
cell line
[90]
Symphytum
officinale L.
Root Glycopeptides Inhibition of PGs and leukotriens release via ;
expression of phospholipase A2
[96]
Ziziphus spina-
christi (L.) Willd.
Bark/ethanol extract – Inhibition of PG synthesis by COX-2
AChE acetylcholinesterase, Akt protein kinase B, BuChE butyrylcholinesterase, COX cyclooxygenase, Hela human uterine cervical carcinoma, IL
Interleukin, iNOS inducible NO synthase, LPS lipopolysaccharide, MCF7 breast epithelial adenocarcinoma, MDA-MB-468 human breast car-
cinoma cell line, NF-jBnuclear factor-kappa B, NO nitric oxide, p38MAPK p38 mitogen-activated protein kinase, PG prostaglandin, ROS
reactive oxygen species, THP-1human acute monocytic leukemia cell line, TNF tumor necrosis factor, VCAM1 vascular cell adhesion protein 1
24 Arch Gynecol Obstet (2015) 292:21–35
123
Table 3 In vivo studies on plants used for treatment of AUB mentioned in ‘‘Canon of Medicine’’
Plant Part/extract Active constituent Model Species Result Reference
Boswellia carteri Birdw. Gum resin/
water extract
– Formalin-and carrageenan-induced paw
edema/oxytocin-induced dysmenorrhea
Mouse Anti-inflammatory activity/analgesic activity [13]
Resin/
methanol
extract
Triterpene acids TPA-induced inflammation Mouse Anti-inflammatory activity [14]
Cuscuta chinensis Lam. Seed/
methanol
extract
– Acetic acid-induced writhing response and
formalin-induced paw licking methods/k-
carrageenan-induced paw edema
Mouse Antinociceptive activity/anti-inflammatory activity [27]
Seed Flavonoids Sound, light, and electricity were combined
into psychological stress for endocrine
dysfunction model
Rat :Estrogen receptor expression in the hippocampus,
hypothalamus and pituitaries, as well as luteinizing
hormone receptor expression in ovaries
[28]
Cymbopogon flexuosus
(D.C) Stapf.
Leaves Essential oil Acute carrageenan-induced paw edema and the
chronic granuloma pouch models/acetic acid-
induced writhing and tail-flick model
Rat Anti-inflammatory activity/analgesic activity [33]
Cymbopogonwinterianus
Jowitt.
Leaves Essential oil acetic acid-induced writhing and formalin
tests/carrageenan-induced neutrophil
migration
Mouse/
rat
Antinociceptive activity/anti-inflammatory activity [37]
Hyoscyamus niger L. Seeds/
methanol
extract
Coumarinolignan Writhing test and Hot plate method/
carrageenin-induced paw oedema and cotton
pellet granuloma methods
Rat and
mouse
Antinociceptive activity/anti-inflammatory activity [41]
Seeds/
alcoholic
extract
– Formalin test Rat Analgesic effect on acute and chronic pain
thresholds
[42]
Hyoscyamus reticulatus
L.
Aerial parts/
methanol
extract
– Acetic acid-induced writhing test and hot plate
test
Mouse Antinociceptive activity [43]
Juglans regia L. Leaves/
ethanol and
aqueous
extract
– P-Benzoquinone-induced abdominal
constrictiontest
Mouse Antinociceptive activity [45]
Leaves/
ethanol
extract
– Carrageenan-induced hind paw edema Mouse Anti-inflammatory activity [45]
Myrtus communis L. Leaves Myrtucommulone Carrageenan-induced paw edema and
carrageenan-Induced pleurisy
Mouse Anti-inflammatory activity [104]
Aerial parts/
aqueous
and ethanol
extracts
Tannins,
alkaloids, and
flavonoids
Acetic acid-induced writhing and hot plate
tests/xylene-induced ear edema and a cotton
pellet test
Mouse Antinociceptive activity/anti-inflammatory activity [105]
Arch Gynecol Obstet (2015) 292:21–35 25
123
Table 3 continued
Plant Part/extract Active constituent Model Species Result Reference
Nymphaea alba L. Rhizome/ethanol extract Alkaloids, tannins,
glycosides and
flavonoids
Acetic acid-induced writhing test and
formalin-induced paw licking method
Mouse Analgesic activity [54]
Flower/ethanol extract – Acetic acid-induced vascular permeability
and cotton pellet-induced granuloma
Mouse Anti-inflammatory activity [55]
Olea europaea L. Fruits/n-hexane extract – Carrageenan-induced hind paw edema Mouse Anti-inflammatory activity [106]
Leaves/chloroform and methanol
extracts
– Carrageenan-induced paw edema/acetic
acid-induced writhing test
Rat/
mouse
Anti-inflammatory activity/
analgesic activity
[57]
Oil – Xylene ear edema test/formalin, hot plate
and writhing tests
Mouse Anti-inflammatory activity/
analgesic activity
[58]
Leaves Hydroxytyrosol and
oleuropein
Carrageenan-induced paw edema/acetic acid
abdominal constriction test
Rat/
mouse
Anti-inflammatory activity/
analgesic activity
[59]
Onopordum
cynarocephalum Boiss.
& C.I.Blanche.
Aerial parts/aqueous extract – Endotoxin-induced paw edema Rat Anti-inflammatory activity [62]
Paeonia peregrina Mill. Flowers and roots/ethanol extracts – Paw edema Mouse Anti-inflammatory activity [63]
Paeonia suffruticosa
Andrews.
Root/80 % aqueous-ethanol extract Paeonol Lipopolysaccharide-induced endotoxemia Mouse Regulation of pro- and anti-
inflammatory cytokines
[65]
Pistacia lentiscus L. Leaves/aqueous, chloroform, ethyl
acetate and methanol extract
– Carrageenan-induced paw edema Rat Anti-inflammatory activity [68]
Portulaca oleracea L. Aerial parts/ethanol extract – Animal model Rat Estrogenic activity [74]
Aerial part/10 % ethanol extract – Carrageenan-induced paw edema assay/hot
plate method and tail-flick response
Rat/
mouse
Anti-inflammatory activity/
analgesic activity
[75]
Aerial part Polysaccharides In vitro assay on HeLa cell/in vivo assay on
U14 tumor-bearing mice
Mouse Antitumor activity against
cervical carcinoma
[76]
Arial part – Wound healing model Mouse Accelerating wound healing
process
[77]
Punica granatum L. Fruit peel/methanol extract – Hind paw egg albumin test/writhing,
formalin, hot plate and tail-immersion tests
Rat Anti-inflammatory activity/
analgesic activity
[81]
Flower/petroleum ether,
dichloromethane and methanol
fractions
– Carrageenan-induced paw edema/acetic
acid-induced writhing test
Rat/
mouse
Anti-inflammatory activity/
analgesic activity
[82]
Fruit rind, flower and leaves/aqueous-
ethanol (50 %) extract
– Carrageenan-induced paw edema/tail-flick
method
Rat/
mouse
Anti-inflammatory activity/
analgesic activity
[83]
26 Arch Gynecol Obstet (2015) 292:21–35
123
Table 3 continued
Plant Part/extract Active constituent Model Species Result Reference
Peel Punicalagin, punicalin,
strictinin A, and
granatin B
Carrageenan-induced paw edema model Mouse Anti-inflammatory activity [84]
Flower/aqueous and
hydroalcoholic
extract
– Animal model Rat ;K?-induced
contraction in
uterus
[88]
Rhus retinorrhaea
Steud. ex A.Rich.
Leaves/
ethanol
extract
– Carrageenan-induced paw edema model/acetic
acid-induced writhing test
Rat/mouse Anti-inflammatory activity/analgesic
activity
[89]
Solanum
nigrum L.
Fruit/
methanol
extract
– Carrageenan-induced paw edema model Rat Anti-inflammatory activity [91]
Leaves/
chloroform
extract
– Carrageenan-induced paw edema model/
abdominal constriction, hot plate and
formalin tests
Rat/mouse Anti-inflammatory activity/analgesic
activity
[92]
Aerial part/
aqueous
extract
– Tumor-bearing animal Mouse Inhibition of growth of cervical carcinoma
by inducing apoptosis in tumor cells
[93]
Aerial part Polysaccharides Tumor-bearing animal Mouse Growth inhibition effect on U14 cervical
cancer and protective effect on thymus
tissue
[94,95]
Symphytum
officinale L.
Root Glycopeptides Carrageenan-induced paw edema Rat Anti-inflammatory activity [96]
Tragopogon
porrifolius L.
Aerial parts/
methanol
extracts
b-amyrin acetate Carrageenan-induced paw edema model Mouse Anti-inflammatory activity [98]
Ziziphus spina-
christi (L.) Willd.
Leaves/
aqueous
extract
– Writhing test Rat Analgesic activity [100]
Root bark/
aqueous
extract
– Acetic acid-induced writhing, formalin and
thermal (hot plate) tests
Rat and mouse Analgesic activity [101]
HeLa human uterine cervical carcinoma, TPA 12-O-tetradecanoylphorbol-13-acetate, U14 mouse cervical carcinoma
Arch Gynecol Obstet (2015) 292:21–35 27
123
compounds [18–20]. Extracts from different parts of C.
siliqua as well as their main compounds, gentisic acid and
(-)-epicatechin, significantly decreased viability of cervi-
cal cancer cells [21,22].
Cuscuta species
Anticancer activity of Cuscuta species was evaluated in
different human cancer cell lines [23–25]. Different
extracts from C. chinensis and C. epithymum demonstrated
significant reduction in viability of cervical cancer cells
[26]. C. chinensis seeds exhibited antinociceptive and anti-
inflammatory effect in animal model through reducing
inflammatory cytokines and oxidative stress [27]. Flavo-
noids of C. chinensis seeds were effective in the treatment
of ovarian endocrine dysfunction in psychologically stres-
sed rats [28]. C. chinensis seeds also showed estrogenic
activity [29]. Flavonoids, kaempferol and isorhamnetin
seem to be responsible for this estrogenic activity [30].
Cydonia oblonga Mill.
Cydonia oblonga peel polyphenolic extract exhibited
potent anti-inflammatory activity by inhibition of proin-
flammatory effectors [31]. Lipophilic extract of C. oblonga
was a valuable anti-lipoperoxidant agent, but it was inef-
fective as radical scavenger; however, its aqueous extract
exhibited marked antioxidant capacity. Both extracts
inhibited proliferation of cervical cancer cells, although
aqueous extract is more potent in this manner [32].
Cymbopogon sp.
Anti-inflammatory and analgesic activity of different spe-
cies of Cymbopogon were demonstrated in different studies
[33–38]. The anti-inflammatory activity of C. citratus has
been attributed to their polyphenolic compounds, particu-
larly chlorogenic acid, as well as its monoterpenes, citro-
nellol and citral [35,36,39,40]. Essential oil from
C. martini showed anti-inflammatory activity by reducing
proinflammatory cytokines in human acute monocytic
leukemia cells [38].
Hyoscyamus species
Hyoscyamus niger seeds have revealed anti-inflammatory
and analgesic activity in various animal models. Cle-
omiscosin A, a coumarino lignin present in seeds, is
responsible for anti-inflammatory activity [41,42]. Aerial
parts of H. reticulates exhibited a significant antinocicep-
tive activity in animal model [43].
Juglans regia L.
Anti-inflammatory and antinociceptive activities of differ-
ent parts of J. regia have been demonstrated in different
studies [44,45].
Lens culinaris Medik.
Lens culinaris, commonly known as lentil, is an edible
plant and is one of the most nutritious and health-
improving foods. Lentil contains essential macronutrients
such as functional proteins and carbohydrates, essential
micronutrients such as iron, selenium, zinc and other trace
minerals, and bioactive phytochemicals such as phytates
and polyphenols [46,47]. L. culinaris markedly inhibited
COX-2 and PGE
2
production [48].
Myrtus communis L.
Myrtucommulone (non-prenylated acyl phloroglucinol)
from M. communis leaves potently suppressed the biosyn-
thesis of eicosanoids by inhibition of COX-1 and
5-lipoxygenase [49,50]. It has been also shown to inhibit
PGE
2
formation without significant inhibition of the COX
enzymes [51]. The aqueous and ethanol extracts of M.
communis aerial parts showed significant antinociceptive
Table 4 Clinical studies on plants used for treatment of AUB mentioned in ‘‘Canon of Medicine’’
Plant Treatment
group
Control
group
Study design Number of
patients
Treatment
duration
Result Reference
Myrtus
communis
L.
Fruit
syrup
Placebo
syrup
Randomized
double-blind,
placebo-
controlled pilot
study
30 3 months ;Mean number of bleeding days from
10.6 ±2.7 days to
8.2 ±1.9 days and ;use of pads in
Myrtus group
[53]
Portulaca
oleracea
L.
Seed
powder
No
preparation
Uncontrolled pilot
clinical trial
10 3 days ;Duration and volume of bleeding and
normalization of patterns of periods;
The seed powder was ineffective in two
(20 %) patients
[73]
28 Arch Gynecol Obstet (2015) 292:21–35
123
activity and also anti-inflammatory effects against chronic
inflammation in animal model [52]. The efficacy of M.
communis in AUB has been also confirmed during a clin-
ical trial [53].
Nymphaea alba L.
Ethanol extract of rhizome of N. alba has shown more
potent analgesic activity compared to that of paracetamol
in animal models [54]. Moreover, ethanol extract of N.
alba flower showed anti-inflammatory activity [55].
Olea europaea L.
Fruits, leaves and oil of O. europaea have revealed anti-
inflammatory activity in different studies [56–58]. Oleu-
ropein and hydroxytyrosol are phenolic compounds found
in olive leaves exhibiting marked anti-inflammatory and
analgesic activities in animal models [59].
Onopordum acanthium L.
Flowers, fruit and leaves of O. acanthium showed anti-
proliferative activities against cervix epithelial adenocar-
cinoma cells [60]. Extracts from O. cynarocephalum and
O. macracanthum exhibited anti-inflammatory activity [61,
62].
Paeonia species
Ethanol extracts of flowers and roots from P. peregrina
showed anti-inflammatory activity in acute inflammatory
models [63]. P. suffruticosa showed anti-inflammatory
activity through inhibition of proinflammatory cytokines.
Presence of significant level of phenolics mainly paeonol,
as well as trace metal contents in P. suffruticosa may be
associated with its anti-inflammatory activity [64,65].
Paeoniflorin, a glycoside from Paeonia root, showed anti-
proliferative and apoptotic effects on human cervical can-
cer cells [66,67].
Pistacia lentiscus L.
Oleogum resin from P. lentiscus showed anti-inflammatory
activity via inhibition of NO and PGE2 [69,70]. The leaf
extract caused an inhibition of gastric lesions in animal
models [68].
Polygonum aviculare L.
Polygonum aviculare exhibited inhibitory activity on PG
S
biosynthesis [71]. Flavonol glucuronides may be respon-
sible for this anti-inflammatory activity [72].
Portulaca oleracea L.
In a pilot clinical trial, the effectiveness of P. oleracea
seeds on AUB was studied. 80 % of patients reported that
duration and volume of bleeding had reduced and their
patterns of periods had normalized without any serious
adverse events [73]. The aerial parts of P. oleracea aerial
part exhibited estrogenic activity in ovariectomized rats
[74]. It also showed significant analgesic and anti-inflam-
matory properties [75].Water-soluble polysaccharide from
P. oleracea inhibited cervical cancer cell proliferation and
significantly inhibited tumor growth in tumor-bearing mice
[76]. Aerial parts of P. oleracea have accelerated the
wound-healing process by decreasing the surface area of
wound and increasing the tensile strength [77].
Punica granatum L.
Anti-inflammatory and antinociceptive activity of different
parts of P. granatum including leaves, flowers and fruit were
demonstrated in various studies [78–85]. Polyphenol-rich
extract of pomegranate fruit exerted an anti-inflammatory
effect in animal model by inhibiting the production of PGE
2
and NO [86]. 2-Methyl-pyran-4-one-3-O-b-D-glucopyran-
oside, a compound isolated from leaves of P. granatum,
blocked inflammatory pathways [87]. Extracts of P. gra-
natum flower exhibited antispasmodic effect on the uterus of
non-pregnant rats and diminished contraction of uterus [88].
Rhus coriaria L.
However, there is no evidence in Rhus coriaria;ethanol
extract of another species of Rhus,R.retinorrhaea, exhibited
anti-inflammatory and analgesic activity in animal model [89].
Rumex acetosa L.
Antiproliferative activity of R. acetosa extracts against
cervix epithelial adenocarcinoma cell line has been con-
firmed in vitro [90].
Solanum nigrum L.
Solanum nigrum berries and leaves showed significant anti-
inflammatory antinociceptive activity in animal models
[91,92]. Aqueous extract as wells as polysaccharides iso-
lated from S. nigrum exert antitumor activity on cervical
cancer bearing mice [93–95].
Symphytum sp.
A glycopeptide isolated from roots of S. officinale showed
a remarkable, dose-dependent anti-inflammatory effect via
Arch Gynecol Obstet (2015) 292:21–35 29
123
Fig. 1 Mechanisms involved in the management of abnormal uterine bleeding by medicinal plants
30 Arch Gynecol Obstet (2015) 292:21–35
123
decreasing the expression of phospholipase A2 [96]. The
extract of S. officinale suppressed leukocyte infiltration at
the 3rd and 4th hour of the induced inflammation [97].
Tragopogon sp.
Acute anti-inflammatory activity of different extracts from
T. porrifolius was evaluated in animal model. The metha-
nol extract exhibited maximum anti-inflammatory activity.
b-Amyrin acetate has been demonstrated to be responsible
for its anti-inflammatory effect [98].
Ziziphus spina-christi (L.) Willd.
Ziziphus spina-christi bark extract showed anti-inflamma-
tory activity by inhibition of COX-2 enzyme [99]. It also
exhibited antinociceptive properties in animal models [100,
101].
Conclusion
Medicinal plants used in traditional and folk medicine of
different areas may be valuable sources for discovering
new drugs [107–110]. In ‘‘Canon of Medicine’’, a precious
book written in 11 AD by the great Iranian physician
Avicenna, variety of medicinal plants with different phar-
macological activities has been introduced. In this paper,
the medicinal plants claimed to be effective in AUB have
been collected from ‘‘Canon of Medicine’’ and their pos-
sible efficacy and pharmacodynamics in modern medicine
were surveyed. Some of them such as Cydonia oblonga,
Juglans regia,Lens culinaris,Olea europaea, and Punica
granatum have nutritional value and are routinely used in
human diets. Different mechanisms of action could be
considered for these medicinal plants including anti-
inflammatory and antinociceptive properties, antiprolifer-
ative activity on cervical cells, and estrogenic activity
(Fig. 1). Since all of the surveyed plants had been shown
in vitro and/or in vivo anti-inflammatory effects, it could be
concluded that their major mechanism of action is inhibi-
tion of the inflammatory process. Endometrial prostaglan-
dins have important role in the management of
menstruation. In AUB, synthesis of endometrial PG
S
is
increased. Endometrium from women with AUB synthe-
sizes more PGE
2
than PGF
2a
(vasoconstricting PG) [3].
Some of the mentioned plants and phytochemicals
including gum resin of Boswellia carteri, Myrtucommu-
lone, an acylphloroglucinol compound from Myrtus com-
munis, resin of Pistacia lentiscus and polyphenol-rich fruit
extract of Punica granatum have revealed significant
inhibitory activity on production of PGE
2
. Moreover, aerial
parts of P. aviculare have exhibited inhibitory activity on
PG biosynthesis. Ceratonia siliqua L., Cuscuta chinensis
Lam., Cuscuta epithymum L., Cydonia oblonga Mill.,
Paeonia sp., Portulaca oleracea L., Solanum nigrum L.,
Rumex acetosa L. and Onopordum acanthium L. have
shown antiproliferative activity on human cervical cancer
cells. Extract of Cuscuta chinensis and Portulaca oleracea
exhibited estrogenic activity in vitro and in vivo, respec-
tively. Furthermore, flavonoids of Cuscuta chinensis seeds
have been effective in the treatment of ovarian endocrine
dysfunction in psychologically stressed rats. Only two
clinical trials on the efficacy of investigated herbal medi-
cines were found: one on Myrtus communis fruits and
another on Portulaca oleracea seeds. The results of two
studies showed that duration and volume of bleeding had
reduced after treatment with these herbs. If we want to
introduce the most effective herbal remedies for the man-
agement of AUB among these 23 investigated medicinal
plants, Myrtus communis,Portulaca oleracea, and Punica
granatum. could be suggested because of finding higher
levels of evidence for them.
The main active constituents of most of investigated
plants are polyphenolic compounds especially flavonoids
and tannins. Flavonoids have been reported from Ceratonia
siliqua leaves [111], Cuscuta chinensis seeds [30], Cymb-
opogon citratus leaves [112], Juglans regia leaves [113],
Lens culinaris seeds [114], Myrtus communis fruits [115],
Nymphaea alba flowers [116], Olea europaea oil and
leaves [117,118], Paeonia sp. [119], Portulaca oleracea
aerial parts [120], and Punica granatum fruits [121]. Effi-
cacy of micronized purified flavonoid fraction (MPFF) on
treatment of AUB was demonstrated in clinical studies. It
seems that suppression of endometrial prostaglandins is its
possible mechanism of action [122].
Overall, investigation of TIM literatures can lead to the
identification of effective natural medicines for the man-
agement of different ailments such as AUB; however,
conclusive confirmation of the efficacy and safety of these
treatments needs more evaluations.
Conflict of interest We declare that we have no conflict of interest.
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