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386 Seyyed Ahmad Askari etal.
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No. of
Study design
Controlled,
randomized,
single-blind
clinical trial
Prospective
observational
pilot study
Prospective cohort
study
Nonrandomized
clinical trial
Randomized
clinical trial
Double-blind RCT 60 Candidiasis
patients Disease Plant Part of plant Control group
60 Trichomonal
vaginitis
60 Vulvovaginal
candidiasis
190 Recurrent UTIs Combination of
447 Infertility Myristica fragrans Mace (aril) Routine
120 Bacterial
vaginitis
associated
with denture
stomatitis
Duration of
treatment Results
Artemisia absinthium
Quercus infectoria
Combination of HT and
tea tree oil, tabebuia,
Juglans regia, and
copper
Olea europaea,
D-mannose,
cranberry, bearberry,
inulin, Orthosiphon,
Lactobacillus
acidophilus
Myrtus communis Leaves Metronidazole 5 days Efficiency better
Punica granatum Peel Miconazole 15 days Similar laboratory
Aerial parts
Gall
– – 3 months Reduction in
Leaves Not using
Metronidazole 10 days As efficient as
10 days/month
supplement
medication for
IUI
for 1 year
From the 7th day
of menstruation
until the day
before
performing IUI
metronidazole
vaginal signs
(pruritus, burning,
and vulvar
erythema)
Fewer UTI relapses
and less pain
Higher pregnancy
rate but no
significant
difference
than
metronidazole
without any
relapse
outcome to
miconazole
Reference
Ahmad etal.
(2011)
Zullo etal. (2020)
Mainini etal.
(2020)
Kavousi etal.
(2019)
Masoudi etal.
(2016)
César de Souza
Vasconcelos
etal. (2003)

Randomized
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controlled,
double-blind
Randomized
controlled,
double-blind
Double-blind,
randomized,
placebocontrolled
84 Bacterial
vaginitis
120 Vaginitis Quercus infectoria
92 Vulvovaginal
candidiasis
Quercus infectoria Gall Metronidazole 5 days As efficient as
Myrtus communis
Rosa damascena
Punica granatum
Querqus infectoria
Myrtus communis
Nardostachys jatamansi
Gall
Leaves
Petals
Peel
Fruit
Fruit
Rhizome
metronidazole
Metronidazole
and placebo
Placebo 7 days Reduced clinical
7 days Improvement in
clinical
examination,
whiff test
specially for
trichomoniasis
symptoms
(itching, irritation,
and vaginal
discharge)
Afzali etal. (2020)
Askari etal.
(2020)
Khalilzadeh etal.
(2020)
Gynecological Disorders 387

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(direct and vapor) methods. Both essential
oils reduced hyphae development and
caused damage to the cell membrane. According to the hemolysin production assay,
cinnamon leaf and bark essential oils may
inhibit hemolysin production in the studied
C. albicans and C. auris strains. It was con-
cluded that essential oils have significant
antihemolytic and antifungal effects in vitro
against C. auris and C. albicans at low doses
(Tran et al., 2020). Effects of essential oil
and aqueous extract of cinnamon bark on
biofilm formation, growth, and adherence
properties of C. albicans were also evaluated.
Cinnamon bark oil was found to be effective
against preformed C. albicans biofilm. It has
also demonstrated intense antifungal activity. Therefore, both cinnamon fractions may
be promising agents for treating oral infections involving C. albicans due to inhibiting C.
albicans growth, biofilm formation, and adherence (Veilleux and Grenier, 2019). Rangel
etal. evaluated the antifungal activity of essential oil of C. zeylanicum leaves (prepared
via the hydrodistillation method) on Candida
spp. biofilm involved in oral infection. According to the phytochemical analysis, eugenol was found to be the major component
of the C. zeylanicum essential oil (68.96%
v/v). It was found that C. zeylanicum essential
oil has antifungal properties through its effect on the yeast cell wall and toxicity effect
on Candida spp. biofilms (Rangel etal., 2018).
The effect and mechanism of C. zeylanicum
on the gynecological disorder polycystic
ovary syndrome (PCOS) were studied by
using a dehydroepiandrosterone (DHEA)
induced PCOS mouse model. It was determined that cinnamon would lead to a decrease
in insulin, insulin-like growth factor 1 (IGF-1),
and luteinizing hormone (LH), an increase
in serum follicle-stimulating hormone (FSH)
level, and improved cyclicity and ovary
morphology (Dou etal., 2018).
Citrullus colocynthis (L.) Schrad.; basio-
nym: Cucumis colocynthis L.
Marzouk etal. investigated the anticandidal
and antibacterial activity of aqueous and diluted acetone extracts of Citrullus colocynthis
(from the plant’s leaves, stems, roots, and
three maturation stages of its seeds and fruit)
against Gram-positive bacteria (S. aureus
and Enterococcus faecalis), various Candida
spp. (Candida glabrata, Candida parapsilosis,
C. albicans, and Candida kreusei), and Gramnegative bacteria (E. coli and P. aeruginosa).
It was identified that C. colocynthis has anticandidal and antibacterial activity against all
strains applied in the study (Marzouk etal.,
2009). In another research, magnetic iron
oxide nanoparticles (MNPs) were prepared
with improved antibacterial activity by
using hot and cold aqueous extracts of pulp
and seeds of C. colocynth. The antimicrobial
activity of these MNPs was tested against
two Gram-negative (P. aeruginosa and E. coli),
two Gram-positive (S. aureus and Bacillus
subtilis) bacteria, and C. albicans. Both MNPs
generated via pulp extract and cold seed
extract presented comparable antimicrobial
potential against the tested microorganisms. However, C. albicans was the micro-
organism that was least affected (Farouk
et al., 2020). Al-Ardi used Citrullus spinosa
and C. colocynthis nano-extracts for T. va ginalis treatment in vitro. In that study, the
plants’ fruit pulps were used, and aqueous
extracts with the concentrations of 100,
250, and 500 ppm were prepared. It was
identified that each plant could be used as a
substitute for metronidazole after completing animal and human tests (Al-Ardi, 2021).
Corylus avellana L.
Oliveira etal. (2008) investigated the chemical composition, antimicrobial and antioxidant activities of three hazelnut (Corylus
avellana) cultivars. Throughout their research,
these cultivars from Portugal were studied
for their individual chemical composition,
antioxidant capacity, and antibacterial activity. The predominant ingredient of fruits
was fat, ranging from 56 to 61% w/w, with a
nutritional value of roughly 650 kcal per 100
g of fruits. Oleic acid, which ranged from
80.67% v/v, was the most abundant fatty
acid, followed by palmitic, linoleic, and stearic
acids. To analyze samples, gas chromatography/
flame ionization detector (GC/FID) was

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used. The antimicrobial capacity of three
hazelnut cultivars was assessed against
Gram-negative bacteria (P. aeruginosa, E. coli,
K. pneumoniae), fungi (C. albicans, Cryptococ-
cus neoformans), and Gram-positive bacteria
(Bacillus cereus, B. subtilis, S. aureus). The
antioxidant activity of aqueous hazelnut
extracts was concentration-dependent, with
similar results for all cultivars. Generally, all
hazelnut extracts demonstrated excellent
antibacterial activity against Gram-positive
bacteria, indicating that these fruits showed
high bioactivity (Oliveira etal., 2008).
Crocus sativus L.
Carradori etal. investigated the anti-Candida
effects of active agents obtained from Crocus
sativus stigmas (called crocin-1 and safranal)
and semisynthetic derivatives of safranal.
These two active agents could prevent C. al-
bicans germ tube production, an essential
virulence component. In addition to this, more
potent and promising compounds were made
via chemical modification, suggesting that
they could be employed as lead compounds
in developing new anti-Candida agents
(Carradori et al., 2016). By using the agar
well diffusion method, the antimicrobial
activities of methanol and petroleum ether
extracts of saffron stigmas were tested against
fungi (C. albicans, Aspergillus fumigatus, and
Aspergillus niger) and various bacterial strains
(P. aeruginosa, K. pneumoniae, S. aureus, E. coli,
and Proteus vulgaris). The results demonstrated that the methanol and petroleum
ether extracts of saffron stigmas possess a
high antibacterial and antifungal activity
against the bacteria and fungi utilized as
test organisms. Moreover, the extracts were
found to have a much stronger bactericidal
than fungicidal activity, according to the
findings of several antimicrobial tests
(Muzaffar etal., 2016).
Iris species
Leaves of Iris × germanica L. were used to
carry out various tests to investigate the
antibacterial and antifungal activity of plant
extracts obtained with five different solvents
(including n-butanol, ethyl acetate, chloroform, hexane, and water). The disk diffusion
assay was used to evaluate the antibacterial
activity of I. × germanica against eight pathogenic bacteria (S. aureus, B. subtilis, Bacillus
atrophaeus, E. coli, P. aeruginosa, Erwinia
carotovara, K. pneumoniae, Salmonella typhi),
and one fungal species (C. albicans). The
research results demonstrated that the ethyl
acetate and butanol fractions were more
effective in controlling the growth of patho
gens than the chloroform, hexane, and
aqueous fractions. C. albicans, S. aureus,
E. carotovara, B. atrophaeus, and E. coli, which
were more susceptible than other microorganisms, were inhibited by all I. × german-
ica extracts. These findings suggest that
different solvent-extracted samples from
I. × germanica leaves have different antibacterial activity against various microorganisms,
which might be valuable sources of antibiotics
to treat fungal and bacterial infections (Uzair
etal., 2016). Other research investigated the
anti-biofilm activity and chemical composition of 15 methanol extracts of Iris species
against both mono- (S. aureus and P. aeruginosa)
and multi-species oral biofilms (Fusobacterium
nucleatum subsp. nucleatum, Streptococcus
gordonii, Actinomyces naeslundii, and Veillonella parvula). The leaf extract of Iris pallida was
the most efficient one in disrupting existing
biofilms and inhibiting biofilm development
compared to the root and rhizome extracts
(Hoang etal., 2020).
Juglans regia L.
The antimicrobial effects of different parts
of walnut tree were investigated in several
studies. In this context, comparatively high
antifungal (C. glabrata and C. parapsilosis)
properties of peel ethyl acetate extract
against oral Candida strains could be observed
(Noumi et al., 2010). Furthermore, leaves
and bark aqueous extracts inhibited the
growth of Gram-positive (S. aureus and
S.mutans), Gram-negative (E. coli and P. aeruginosa) bacteria species, and C. albicans. Another
study was performed by the agar streak

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dilution method based on radial diffusion
(Pereira et al., 2007b). Ethanol extract of
walnut root disrupted the cell wall and cell
membrane of Candida, applying MIC
imum inhibitory concentration at which
(min-
90
≥90% of strains within a test population are
inhibited) and spot assays (Raja etal., 2017).
Studies performed by other research groups
also presented growth inhibitory effects for
bark extract, crude methanol extract, and
ethyl acetate fractions against S. aureus,
B.subtilis, P. aeruginosa, E. coli, and K. pneumoniae by disk diffusion (Bakht etal., 2017).
Another study approved anti-C. albicans and
anti-herpes simplex virus (HSV) effects of
walnut pellicle ethanol extract by the microdilution method (D’Angeli et al., 2021).
Zullo etal. asserted that patients affected by
vulvovaginal candidiasis showed a reduction
in vaginal signs such as pruritus, burning,
and vulvar erythema after applying a combination of hydroxytyrosol (HT) and other
components containing tea tree oil, Tabebuia
species, J. regia, and copper for a duration of
3 months (Zullo etal., 2020).
Lepidium sativum L.
A research study evaluated the antifungal
activity of Lepidium sativum seeds using various
hexanic and alkaloidal extracts to determine
the growth of C. albicans. The authors noticed
that there is a significant link between inhibition of crucial enzymes involved in cellular
metabolism and invasion mechanisms, which
then inhibits the growth of C. albicans (Gacemi
etal., 2020).
Myristica fragrans Houtt.
Setty et al. (2020) investigated Myristica
fragrans (nutmeg) antimicrobial effects on
primary tooth pathogens. M. fragrans essential oil was prepared via hydrodistillation by
Clavenger’s method and thin-layer chromatography (TLC), gas chromatography–mass
spectrometry (GC–MS) analysis, and highperformance TLC were used to determine
the individual phytoconstituents. It was
deduced that M. fragrans active components,
including myristicin, myristic acid, trimyristin,
elemicin, and safrole, are effective against
E. coli, S. aureus, E. faecalis, S. mutans, C. albic ans,
L. casei, A. viscosus, Prevotella intermedia, and
Porphyromonas gingivalis. Thus, the essential
oil of nutmeg fruits shows good antimicrobial activity (Setty et al., 2020). Therefore,
extracts obtained from M. fragrans fruits
represent potent inhibitors of S. mutans already
at a very low inhibitory concentration of
3.9 μg/ml, which is significantly lower than for
other natural anticariogenic agents (Chung
etal., 2006). Another research detected nutmeg seed extract’s antifungal activity against
oral candidal infection (C. albicans). Compared
to nystatin as a positive control, the nutmeg
extract showed antifungal activity with an
effective zone of inhibition ranging from
18.0 to 12.0 mm (Iyer etal., 2017). It has
been investigated whether using honey and
1% w/w extract of M. fragrans as a vaginal
tablet affects the extent of success of intrauterine insemination (IUI) or not. In a nonrandomized clinical trial, 447 women with
infertility problems participated. They used
the vaginal tablet from the seventh day of
menstruation until the day before performing IUI. It was observed at study end that
the use of this vaginal product for a more
extended period and across several menses
cycles before IUI might produce more positive results (Kavousi etal., 2019).
Myrtus communis L.
Different studies show that myrtle (Myrtus
communis) leaves have a promising pharmaco-
logic efficacy. Aqueous and ethanol crude
extracts demonstrate antimicrobial effects
against Gram-positive (S. aureus and E. fecalis)
and Gram-negative (E. coli, P. vulgaris, Serratia
marcescens, A. baumannii, K. pneumoniae,
P.aeruginosa) bacteria (Mun’im R. etal., 2009).
All crude extracts, including methanol, ethanol,
ethyl acetate, and acetone extracts, showed
good antifungal activity against C. albicans
(Erdogan eta l., 2014). Many other studies confirmed antibacterial (Mansouri et al., 2001;
Al-Saimary et al., 2002; Alem etal., 2008),

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antifungal (Cannas e tal., 2014), antiviral (Jassim
and Naji, 2003), and antiprotozoal (Azadbakht
etal., 2003; Mahdi etal., 2006) effects of myrtle.
In another study, myrtucommulone obtained
from myrtle leaves exhibited potent antiinflammatory effects in vivo when administered to mice intraperitoneally (Rossi etal.,
2009). Using an in vitro model (lipopolysaccharide-stimulated macrophages) demonstrated
that myrtle essential oil has anti-inflammatory
properties. Two studies about ethanol extracts
showed the anti-inflammatory effect of myrtle
leaves in rats (Al-Hindawi et al., 1989; Sen
etal., 2017). Five-day use of M. communis and
Berberis vulgaris has been reported to be more
effective than metronidazole in patients with
bacterial vaginitis without relapse (Masoudi
etal., 2016).
Ocimum basilicum L.
A study was conducted to investigate the
effect of mastic essential oil from Ocimum
basilicum and Pistacia lentiscus on trophozoites of T. vaginalis. At several time intervals
(after 24, 48, 72, and 96 h), the authors
determined the effects of different concentrations of P. lentiscus mastic (15, 10, and 5
mg/ml) and O. basilicum essential oil (30, 20,
and 10 mg/ml) on trophozoite proliferation.
According to the results obtained, both
O. basilicum and P. lentiscus mastic inhibited
the growth of T. vaginalis trophozoites via
extensive vacuolization of the cytoplasm
and causing damage to its membrane. Thus,
it could be concluded that phytotherapeutic
agents such as O. basilicum and P. lentiscus
mastic oil may be effective in treating trichomoniasis (Ezz Eldin and Badawy, 2015).
Another study investigated the antimicrobial
activity of five different plant varieties against
a wide range of foodborne Gram-negative
bacteria, Gram-positive bacteria, molds, and
yeasts. An agar well diffusion method was
used to test essential oils of sweet basil
(O. basilicum) obtained by hydrodistillation.
Except for Pseudomonas species and Flavi-
monas oryzihabitans, all five different basil
essential oils demonstrated antimicrobial
activity against most of the tested organisms
(Lachowicz etal., 1998).
Olea europaea L.
Various researchers have examined olive
leaves for their antimicrobial effects on oral
pathogens like C. albicans, food-related
bacteria, E. coli, and B. cereus, by macro and
micro broth dilution and agar disk diffusion.
Aqueous, methanol, and acetone extracts
showed potent inhibitory effects (Markin
etal., 2003; Pereira etal., 2007a; Karygianni
etal., 2014; Edziri etal., 2019). A prospect-
ive cohort study investigated the prevention
and treatment of menopausal cystitis by a
nutraceutical product containing -mannose,
inulin, cranberry, bearberry, olive oil,
Orthosiphon leaves, and L. acidophilus. In
that study, 190 patients with recurrent urinary
tract infection (UTI) used this nutraceutical
product 10 days per month for 1 year. At
study end, it was observed that users had
fewer UTI relapses and less pain (Mainini
etal., 2020).
Phoenix dactylifera L.
Recently, Sahyon and Al-Harbi (2020) provided
a novel combination of heart of Phoenix
da ctylifera (HP) extract loaded on chitosan
nanoparticles and assessed its antibacterial,
antioxidant, anticancer, and free radical scavenging potential (in vitro). The HP extract and
HP extract loaded on chitosan nanoparticles
(HP–ChNPs) were tested against two Gramnegative bacteria, E. coli and K. pneumoniae,
and three Gram-positive bacteria, i.e., S. aureus,
B. subtilis, and B. cereus. In addition to this, the
antifungal activity of the HP extract and
HP–ChNPs was tested against C. albicans. The
agar disk diffusion method was used to evaluate the antibacterial activity of the HP–ChNPs
and the HP extract (Sahyon and Al-Harbi,
2020). Soxhlet extraction (70°C, 6 h) was used
to prepare a hydroalcoholic (2:8, v/v) extract of
the P. dactylifera fruit pulp. Silver nanoparticles
were synthesized using an aqueous solution
(20% v/v) of the extract (AgNPs). The disk
diffusion experiment revealed that the plant–
nanosilver broth had effective antimicrobial
action against E. coli ATCC 8739, S. aureus ATCC
6538, and C. albicans ATCC 10231. However,

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it was found that the plant extract has no
antibacterial action (Shaikh etal., 2018). Other
researchers used a root extract of P. dactylifera
to produce silver nanoparticles (AgNPs) to
evaluate their anticancer and antimicrobial
potential (against C. albicans and E. coli). According to the results obtained, it was concluded
that biologically generated AgNPs have multifunctional capabilities and might be employed
to treat human cancer and other infectious
diseases (Oves etal., 2018). The antimicrobial,
anticancer, and antioxidant activities of chitosan
nanoparticles loaded with an extract of
P. dactylifera tree (HP–ChNPs) were studied in
rats receiving doxorubicin-induced cardiotoxicity and nephrotoxicity. Result showed that the
HP–ChNPs reduced cardiac and renal apoptosis
and increased the level of programmed cell
death protein-1 (PD-1) (Sahyon and Al-Harbi,
2020).
Pimpinella anisum L.
Vieira et al. found that several essential oils
isolated from Apiaceae species, especially anise
seeds, have a potent inhibitory effect against
Candida spp., as detected by the broth microdilution technique (Vieira etal., 2019).
Pistacia lentiscus L.
Milia et al. (2020) screened activity of
P. lentiscus essential oil, obtained from wild
plant leaves grown in North Sardinia (Italy),
against Candida spp. and periodontal bacteria.
It was found that P. lentiscus essential oil has
a broad spectrum of activity against various
Candida fungi species and periodontal bacteria. In this context, the authors also found
a dual inhibitory effect with regard to the
two enzymes cyclooxygenase (COX-1/2) and
lipoxygenase (Milia etal., 2020).
this widespread plant species is rich in n-3
fatty acids, alkaloids, oxalic acid, coumarins,
cardiac glycosides, flavonoids, and anthraquinone glycosides. Throughout the research,
the agar well diffusion method was carried
out to evaluate the antibacterial activity
of different root extracts against E. coli,
B. subtilis, Enterobacter cloacae, C. albicans,
K. pneumoniae, Micrococcus luteus, S. typhi,
P.aeruginosa, Shigella dysenteriae, S. aureus,
and Streptococcus agalactiae, which are respon
sible for the spread of common illnesses in
Nigeria. Except for P. aeruginosa, K. pneumo-
niae, and M. luteus, all extracts demonstrated
a high MIC against the pathogens. For the
first time, P. oleracea was found as an effective
antibacterial agent, confirming the plant’s
ethnomedicinal usage. Another study investigated the antimicrobial activity of liquid
carbon dioxide (CO2) extracts of P. oleracea
antimicrobial activity was assessed against
S. aureus ATCC 6538-P, B. subtilis ATCC
6633, E. coli ATCC 8739, and C. albicans
ATCC 10231 by the disk diffusion method
and micro method of serial dilution. It was
concluded that the CO2 extracts of P. oleracea
contain several bioactive components with a
considerable antibacterial activity (Tleubayeva
etal., 2021). In a study aimed to investigate
anti-Candida activities of several medicinal
plants, to choose a herbal medicine for use as
an effective antibacterial in humans, ethanol
extracts of seven different plants such as
P. ol er ac ea (baq’lah), Avicennia marina (qurm),
Fagonia indica (sh ok a’a ), Salvadora persica
(souwak), Ziziphus spina-christi (sidr), Lawsonia
inermis (henna), and Asphodelus tenuifolius
(kufer) were used. It was found that L. inermis
and P. oleracea extracts are likely to be prom-
ising drugs for treating multidrug-resistant
(MDR) bacteria and C. albicans in humans
(Soliman etal., 2017).
Portulaca oleracea L.
In a study performed by Ojah etal. (2021),
root extracts of Portulaca oleracea were tested
for their antibacterial activity. Generally,
Punica granatum L.
Both fruit and peels of Punica granatum
(pomegranate) exhibited significant antimicrobial activity. Microparticles synthesized from
ethanol extract of peel show antifungal activity

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against C. albicans by the broth microdilution
reference procedure of the Clinical and
Laboratory Standards Institute (CLSI) (Endo
etal., 2012). Anibal and co-workers confirmed
that ethanol extract of whole pomegranate
fruit has excellent antimicrobial activity
against C. parapsilosis, Candida utilis, Candida
lusitaniae, and C. glabrata through the M27-A2
broth microdilution reference procedure of
CLSI (Anibal etal., 2013). In another study,
antifungal activity of methanol and ethanol
extracts of pomegranate bark and root
against C. albicans and C. glabrata could be
proven via the broth dilution antifungal sus
ceptibility test (Lavaee etal., 2018). Furthermore, methanol extracts of pomegranate
peel demonstrated inhibitory effect against
a range of microorganisms such as S. aureus,
K. pneumoniae, B. subtilis, M. luteus, E. coli, C.
albicans, and A. niger by applying the well
diffusion method of the National Committee
for Clinical Laboratory Standards (NCCLS)
(Qabaha, 2013). Aqueous extracts obtained
from the mesocarp of pomegranate fruits
could also be used as suitable agents against
S. mutans, Streptococcus mitis, and C. albicans
(Mehta etal., 2014). The in vivo antifungal
activity of acetone extracts of P. granatum,
Quercus suber, and Vicia faba against C. albicans
and Trichophyton mentagrophytes was tested
in another study using immunosuppressed
mice as test animals. There, a decreased mortality of C. albicans and moderate-activity
molds was observed (Akroum, 2017). Evaluating
the in vivo antifungal activity of the pomegranate peel extract against oral candidiasis in
Wistar rats and comparing it to nystatin were
aims of a study in which rats were immunosuppressed by cyclosporine and hydrocortisone
acetate, got infected, and then were cured.
Not only did that study present a decreasing
growth of C. albicans but the rats were completely cured in all doses after 15 days of
treatment (Bassiri-Jahromi, 2018). Accordingly, pomegranate extracts alter the mouse
microbiome and dysbiosis caused by Citro-
bacter rodentium infection by decreasing the
pathogenicity of C. rodentium infections and
actinobacteria and increasing the abundance
of proteobacteria and verrucomicrobia (Ge orge
etal., 2019). The novel plant extract product (Grazix™) can affect weaned piglets’
performance and gut health when challenged
with E. coli. This product is a standardized
mixture of green tea leaves (Camellia sinensis)
and pomegranate fruit obtained using the
LiveXtract™ process. Including this product
in the diet of post-weaning piglets would
increase the average daily gain, gut health, and
microbial ecology as well as decrease the
severity of an E. coli challenge (Bontempo
etal., 2014). The effect of adding pomegranate seed extracts to fat-containing diets on
nutrient digestibility, intestinal microflora,
and performance of broilers has been investigated and reported to increase the digestion
of fat-containing diets, crude fat digestibility,
and cecum Lactobacillus count (Rezvani etal.,
2018). A similar laboratory outcome to miconazole was reported when using P. granatum as
an antifungal agent for 15 days against candidosis associated with denture stomatitis
(César De Souza Vasconcelos etal., 2003).
In a single-arm clinical trial, the effect of
pomegranate extract on stool microbial composition was studied. Here, participants were
20 healthy volunteers, and the study duration
was 4 weeks. In this context it was demonstrated that consumption of pomegranates
may have health benefits due to the formation
of ellagitannin metabolites, which can be
attributed to changes in the microbiota (Li
etal., 2015).
Quercus infectoria G. Olivier
Chusri and Voravuthikunchai (2011) were
able to show the antimicrobial activity of
Q.infectoria gall against S. aureus and methicillin-resistant Staphylococcus aureus (MRSA)
by applying ethanol extracts due to hypersensitivity to low and high osmotic pressure
using MIC/minimum bactericidal concentration (MBC). Also, methanol and aqueous
extracts of gall displayed substantial activity
against C. albicans, Candida krusei, C. glabra-
ta, C. parapsilosis, and Candida tropicalis
using the twofold serial dilution technique
(Baharuddin etal., 2015). The efficacy of
Q. infectoria and Mimusops elengi on gingivitis
inhibition has been also reported in a study
in which 20 patients with the problem of

394 Seyyed Ahmad Askari etal.
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chronic gingivitis participated. The intervention group used this combination for 7 days,
while the control group used Listerine mouthwash. At the end of this double-blind, randomized controlled trial (RCT), it could be
shown that the herbal preparation was efficient but less so than Listerine (Choudhary
etal., 2015). Another RCT investigated the
effect of taking myrtle and oak gall as vaginal
suppositories for vaginitis. That study involved
a total of 120 patients in three groups, includ
ing a placebo control group taking metronidazole and an intervention group. It lasted
7 days, and it turned out that myrtle and oak
gall consumption led to improvement in
clinical examination, whiff test, especially
for trichomoniasis, and resulted in similar
treatment efficacy to metronidazole (Askari
etal., 2020). In an RCT performed on bacterial
vaginitis, oak gall was found to be even more
efficient than metronidazole. The duration
of that study was 5 days, and 84 patients
took part (Afzali et al., 2020). In another
RCT against vulvovaginal candidiasis,
92 patients were divided into two groups (a
placebo group and an intervention group) in
which the patients took a vaginal tablet
containing Rosa × damascena, P. granatum,
Q. infectoria, M. communis, and Nardostachys
jatamansi for 7 days. It was shown that the use of
this vaginal tablet significantly reduced clinical symptoms such as itching, irritation, and
vaginal discharge (Khalilzadeh etal., 2020).
and hexane extracts) showed good antibacterial activity against Mycobacterium smeg-
matis, B. subtilis, and B. subtilis var. niger and
antifungal efficacy against C. albicans via the
agar well diffusion method (Ulukanli et al.,
2005). Alcoholic extracts of Rumex dentatus
expressed growth-inhibitory effects on
C. albicans and Acremonium spp. by agar disk
diffusion (Humeera etal., 2013). Synthesized
nanoparticles of Rumex hymenosepalus root
played a significant role in growth inhibition
against E. coli, C. albicans, Gram-positive, and
Gram-negative bacteria, dose-dependently,
when applying the well diffusion method
(Rodríguez-León et al., 2018; VillalobosNoriega etal., 2021). Furthermore, it was
proven that aqueous extract of Rumex nervosus
aerial parts was able to inhibit the growth of
Gram-positive bacteria (Al-Asmari e tal., 2015).
Tamarix species
Both Tamarix africana and Tamarix aphylla (L.)
H. Karst. showed antifungal effects against C.
albicans when hydroalcoholic extracts of the
aerial parts were applied using the agar disk
diffusion method. In addition, T. aphylla was
found to have inhibitory effects against E. coli,
E. faecalis, K. pneumoniae, P. aeruginosa, and
MRSA (Chekroun-Bechlaghem et al., 2019;
Al-Omar etal., 2020).
Rubus fruticosus L.
Recently, synthesized silver nanoparticles of
an aqueous decoction of Rubus fruticosus
fruit showed an inhibitory effect against
E. faecalis and C. albicans by the microdilution
method. This activity may be related to the
high ellagic acid content of R. fruticosus berries
(Ekrikaya etal., 2021).
Different species of the Rumex genus possess
antimicrobial activity. For example, roots
and aerial parts of Rumex crispus (acetone
Rumex species
Thymbra capitata (L.) Cav.; basionym:
Satureja capitata L.
Pinna etal. (2019) aimed to determine the
antimicrobial effects of Citrus limon var.
pompia Camarda extract and Thymbra capitata
essential oil, either incorporated in vesicular
nanocarriers or as raw extracts, against
C. albicans and S. mutans. Both nanovesicles
and raw extracts demonstrated no activity
against human gingival fibroblasts at all
dosages examined (1, 10, and 100 μg/ml).
The highest antimicrobial activity of T. capitata
against S. mutans and C. albicans was demonstrated by applying the time–kill assay, disk
diffusion method, MIC/MBC/minimum
fungicidal concentration (MFC) assay, and

Gynecological Disorders 395
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transmission electron microscopy (TEM)
(Pinna etal., 2019). Another study screened
biofilm inhibition via loading of essential
oils on biocompatible poly(ε-caprolactone)
nanocapsules. Essential oils distilled from O.
vulgare and T. capitata (thymol and carvacrol
chemotype) were encapsulated in
poly(ε-caprolactone) nanocapsules, which
were biocompatible. The mentioned nanosystems demonstrated antifungal, antibiofilm,
and antibacterial activities against C. albicans,
E. coli, and S. aureus. It was revealed that the
polymeric nanocapsules loaded with thyme
and oregano essential oils could inhibit microbial and biofilm formation, which might
be an ecological alternative in developing
novel antimicrobial strategies (Kapustová
etal., 2021). Further research evaluated the
combined effects of conventional drugs with
C. verum and T. capitata essential oils against
elucidation of the molecular mechanism of
action and biofilm formation in C. albicans.
It was identified that T. capitata and C. verum
essential oils were significantly effective
against biofilm formation in C. albicans with
80.6 and 85.57% inhibition, respectively, at
half MIC values. Moreover, essential oils
reduced the synthesis of secreted aspartic
proteases by more than 90% at 0.75 × MIC.
Essential oils reduced the expression of
adhesion and secreted aspartyl proteinase
virulence factor genes when used in conjunction with amphotericin B. As a result,
C. albicans biofilm on medical devices could be
effectively treated when using C. verum and
T. capitata essential oils in conjunction with
amphotericin B (Essid etal., 2019). The primary purpose of another study was to characterize, extract, and formulate the essential
oil obtained from T. capitata in phospholipid
vesicles: glycerosomes, liposomes, and penetration enhancer-containing vesicles (PEVs).
Here, carvacrol was the major component of
the steam-distilled essential oil that was
found to have antibacterial activity against
L. acidophilus, Streptococcus sanguinis, and
S.mutans. Therefore, various Thymus essen-
tial oil formulations may be helpful for the
treatment of oral cavity diseases due to the
combination of antibacterial and antioxidant
activities (Manconi etal., 2018).
Conclusion
Vaginosis is one of the most typically encountered problems by a gynecologist. Many wome n
frequently self-treat with over-the-counter
(OTC) medicines and may present to their
healthcare provider after treatment failure.
Candidiasis (20 to 25% of cases), BV (40 to
50% cases), and trichomoniasis (15 to 20%
cases) may occur as repetitive episodes
and are therefore associated with significant
treatment costs and morbidity (Paladine
and Desai, 2018). Because of treatment failures and recurrent infections, there is not
any completely satisfactory treatment for
vaginitis in current medicine. Therefore,
finding new sources of drugs is necessary to
develop new medications for these conditions.
In TPM, vaginitis is named sayalān-e rahem,
which means excessive vaginal discharge.
As a prominent physician of TPM, Avicenna
recommended several medicinal plants for
the treatment of vaginitis (Table 12.1). Natural remedies were always a potential source
of new medicines. Therefore, in this chapter, the medicinal plants recommended by
Avicenna in his Canon of Medicine have been
presented, along with current scientific
evidence-based results. According to TPM
the first step in the treatment of vaginosis
is the elimination of the pathogen. Most
of the herbs mentioned here have been
confirmed in in vitro studies as excellent
antimicrobial agents and the postulated
antibacterial, antifungal, and antiprotozoal
effects could be confirmed. In the second
step, Avicenna emphasized the use of uterus
tonics after treatment to prevent recur
rence of the disease. Some of the plants
studied in this context could play a very
prominent role in strengthening normal vaginal flora, such as pomegranate (Punica
granatum).
The highest level of evidence came from
in vitro studies, but generally there are still
too few animal studies or clinical trials.
More research is therefore needed to better
utilize the existing options of TPM in the
development and administration of new
pharmaceutical formulations also in the treatment of vaginosis.
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