Pharmaceutics 14 00171

pharmaceutics
Review
Herbal Medicines—Are They Effective and Safe
during Pregnancy?
Beata Sarecka-Hujar 1, * and Beata Szulc-Musioł 2
1 Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec,

Medical University of Silesia in Katowice, Kasztanowa Str. 3, 41-200 Sosnowiec, Poland
2 Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences in Sosnowiec,
Medical University of Silesia in Katowice, Kasztanowa Str. 3, 41-200 Sosnowiec, Poland; bszulc@sum.edu.pl
* Correspondence: beatasarecka@poczta.onet.pl or bsarecka-hujar@sum.edu.pl; Tel.: +48-32-269-9830
Abstract: Since the teratogenicity of Thalidomide has been proven, herbal products are more com-
monly used in pregnancy to not only relieve morning sickness but also to fight infections. These
products are frequently considered as natural and therefore harmless. However, herbs contain a
number of active substances that, when used during pregnancy, can affect the development of the
fetus. Often, pregnant women do not consult the usage of herbal medicines with a physician. The
access to these products is easy and treatment of certain ailments with the use of herbs is common
in many countries. The aim of the present literature review was to discuss available data regarding
the efficacy and safety of cranberry, chamomile, Echinacea purpurea, garlic, ginger, Ginkgo biloba,
and peppermint, which are used to counteract the most common ailments during pregnancy, i.e.,
infections and pregnancy-related ailments (e.g., nausea and vomiting, dizziness, and headache).
Analysis of available data showed that ginger is one of the most extensively analyzed herbal remedies.
The dose of ginger below 1000 mg per day may help to relief hypereremesis gravidarum, and such an
amount of ginger did not increase frequency of adverse effects for either woman or developing fetus.

Data regarding other herbs are most often heterogeneous and give conflicting results with no clear
conclusions. However, all herbal products should be used with a special caution in pregnancy. Fur-
Citation: Sarecka-Hujar, B.; ther high-quality human studies should be determined to confirm the safe doses of herbal products
Szulc-Musioł, B. Herbal which could be used by pregnant or breast-feeding women.
Medicines—Are They Effective and
Safe during Pregnancy? Pharmaceutics Keywords: herbs; herbal medicines; ginger; cranberry; garlic acid; Ginkgo biloba; Echinacea purpurea
2022, 14, 171. https://doi.org/
10.3390/pharmaceutics14010171
Academic Editor: Cheong-Weon Cho

1. Introduction
Received: 30 October 2021
Accepted: 8 January 2022
For centuries, herbal products have been used to treat various diseases in different re-
Published: 12 January 2022
gions of the world. A number of herbal medicines contain antimicrobial, anti-inflammatory,
and immunomodulatory properties and may be used in treatments e.g., of infections. In
Publisher’s Note: MDPI stays neutral
general, the use of herbs during pregnancy is not advisable due to their possible impact
with regard to jurisdictional claims in
on the fetal development. Numerous experimental studies were earlier conducted to
published maps and institutional affil-
analyze the effect of extracts from various herbs on mice or rats fetuses. However, avail-
iations.
able results are often contradictory. Some of the studies showed morphological and toxic
effects of herbal extracts on animal progeny while others did not [1–3]. In the study by
Lewicki et al. [1], pregnant and lactating mice were fed with aqueous and hydro-alcoholic
Copyright: © 2022 by the authors.
extracts of Rhodiola kirilowii as well as epigallocatechin (EGC), which is an antiangiogenic
Licensee MDPI, Basel, Switzerland. compound of Rhodiola extracts. Authors found some morphometric anomalies in the kidney
This article is an open access article structure in the offspring of mothers fed with hydro-alcoholic extracts of Rhodiola kirilowii
distributed under the terms and or EGC. On the contrary, application of Scutellaria baicalensis extract demonstrated no
conditions of the Creative Commons significant effects in fetal parameters in three groups of mice receiving 2, 8 or 32 g of
Attribution (CC BY) license (https:// extract/kg/day. However, a high dose of Scutellaria baicalensis was suggested to have
creativecommons.org/licenses/by/ some potential maternal toxicity because absolute liver and kidneys weights were sig-
4.0/). nificantly increased in the group receiving 32 g of this herbal extract/kg/day compared
Pharmaceutics 2022, 14, 171. https://doi.org/10.3390/pharmaceutics14010171 https://www.mdpi.com/journal/pharmaceutics

Pharmaceutics 2022, 14, 171 2 of 27
to controls [2]. Similarly, in the case of Boehmeria nivea, no embryotoxicity in mice was
observed but significantly lower viability of embryonic stem cells was demonstrated [3].
Since the teratogenicity of Thalidomide has been proven, herbal medicines are more
commonly used during pregnancy to relieve pregnancy-related symptoms and help fight
infections, among others. Herbs are frequently considered as natural and therefore harmless.
However, these products were suggested to influence the CYP superfamily, which is
responsible for 65–80% of all CYP-mediated drug metabolism [4]. Some of the herbs which
were observed to be used by pregnant women show potent inhibition into the following:
CYP1A2 (black elderberry, ginger, and horsetail), CYP2D6 (fennel and raspberry leaf), and
CYP3A4 (fennel and raspberry leaf) [5].
Pregnant women usually do not consult the use of herbs with a doctor or pharma-
cist [6]. Data demonstrated that almost 95% of Ethiopian pregnant women did not consult
the usage of herbal medicines with the doctor or nurse [7]. In Norway, only less than 12%
of pregnant women were recommended to use herbs by healthcare personnel [8]. Such a
situation results from the fact that future mothers are not aware that herbs contain active
substances that can cause miscarriage, premature birth, uterine contractions, or injury to
the fetus. On the other hand, the clinicians do not always have sufficient knowledge on the
safety of using herbal medicines during pregnancy and while breastfeeding.
Previously, it was demonstrated that a large number of women used many types of
herbal medicines for different purposes during their pregnancies [9]. The use of herbal
medicines by pregnant women differs between Europe and USA, reaching from 27% to 57%
or even more in Europe and from 10% to 73% in the USA [10]. In a study of 400 pregnant
Norwegian women, the prevalence of herbs use was 36% and surveyed women indicated to
using nearly 250 herbal products containing 46 different herbs [8]. Conversely, in southern
Italy, 81% of pregnant women indicated the use of at least one herbal product during
pregnancy [11]. Interestingly, the frequencies of Australian women using herbal remedies
during pregnancy and while breastfeeding were lower (14% and 10%, respectively) [12].
Previously, complementary and alternative medicine (CAM), which includes phytotherapy,
was demonstrated to be used by women between 31–40 years of age with higher educational
levels, and they also used CAM in their earlier pregnancies [13]. Nevertheless, the problem
of the use of herbs during pregnancy is noteworthy, because it concerns both the developing
fetus and the woman.
The aim of the present literature review was to discuss available data regarding the
efficacy and safety of the herbal products (cranberry, chamomile, Echinacea purpurea, garlic,
ginger, Ginkgo biloba, and peppermint) used to counteract the most common ailments
during pregnancy. The results of surveys and clinical trials concerning the effects of the
selected herbal medicines on developing fetus as well as the results of the experimental
studies performed in animals were discussed in the present review.
2. Methodology
We searched PubMed, Google Scholar, and Embase using the following keywords
in different combinations: “pregnancy”, “pregnant women”, “labor”, “herbs”, “herbal
medicines”, “cranberry”, “chamomile”, “Echinacea purpurea”, “garlic”, “ginger”, “Ginkgo
biloba”, and “peppermint” (last search November 2021). In the present literature review,
we focused our attention on herbs that are frequently used for the most common ailments
during pregnancy: (1) herbs used to counteract urinary infections and upper respiratory
tract infections, i.e., cranberry, Echinacea purpurea, and garlic; (2) herbs used to counteract
some pregnancy-related symptoms (nausea and vomiting, dizziness, and headache), i.e.,
chamomile, ginger, Ginkgo biloba, and peppermint. We included experimental data on
animals, as well as clinical trials and surveys on pregnant women. Finally, we discussed
the results which we believed were the most interesting or relevant.
3. Herbal Medicines Used to Counteract Infections during Pregnancy

3.1. Cranberry (Vaccinium macrocarpon)
Vaccinium macrocarpon (American cranberry; also known as large cranberry) belongs
to the Ericaceae family. It is native to North America, growing across the United States and
Canada, and its fruits are large, spherical red berries. In contrast, wild growing swamp
cranberry (Vaccinium oxycoccus) is characterized by smaller fruits. Cranberries contain
the highest total phenolic amount and are characterized by a highest total antioxidant
capacity compared to other fruits [14,15]. The antioxidant activity is related to the presence
of three main classes of flavonoids: anthocyanins, flavonols, and flavan-3-ols, which play
an important role in the prevention of bacterial infections, especially urinary tract infections
(UTI) [16,17]. Previously it was demonstrated that cranberry extracts reduce C-reactive
protein (CRP) and proinflammatory interleukins but increase synthesis of nitric oxide [17].
In addition, oral administration of anthocyanin from bilberry (Vaccinium myrtillus) resulted
in endothelium-dependent vasodilation through the activation of the NO-cGMP signaling
pathway in hypercholesterolemic individuals [18]. Cranberries or products containing
cranberry extracts are often recommended for the treatment of UTI, also during pregnancy.
In an experimental study by Bałan et al. [19], pregnant and lactating mice were fed
with American cranberry extract of a daily dose of 0.88 mg. The authors observed some
differences in the progeny’s spleens, more CD19+ and CD8+ lymphocytes in the cytometry
analysis of spleen cells, higher serum concentration of VEGF and bFGF, as well as an
increase in the diameter of kidneys glomeruli in the offspring from the cranberry group
compared to the control group. However, no differences were seen in the response to
immunization by red blood cells of sheep, and no abnormalities in creatinine and urea
serum level were also observed in progeny of mice fed with cranberries [19].
As to studies on humans, in the study by Wing et al. [20], none of the 14 pregnant
women receiving cranberry capsules to treat URI had antepartum complications, i.e., fetal
malformation, intrauterine fetal growth restriction, oligohydramnios, or polyhydramnios.
Neonatal outcomes were similar between the study and placebo groups, however 1-min
Apgar score < 7 was more frequent in the cranberry group (21%) than in the placebo group
(0%). Similarly, in a large cohort of Norwegian pregnant women, in which 1.3% of women
had used cranberry, no increased risk of congenital malformations after its usage was also
observed [21]. Another Norwegian survey among pregnant women showed that 6% of
future mothers used cranberry for treatment of UTI [22]. Statistically significant differences
in urinary interleukin-6 level was demonstrated when comparing pregnant women con-
suming cranberry juice and placebo group (receiving beverage without cranberry) [23].
Conversely, according to four Brazilian medical societies, there is weak evidence to support
the use of cranberries and cranberry-derived dietary supplements in the treatment of lower
urinary tract infections in pregnant and non-pregnant women [24]. Table 1 presents the
characteristics and findings of selected studies, evaluating the use of cranberries during
pregnancy, both in animals and humans.
3.2. Echinacea purpureae L. (Moench.)

The Echinacea purpurea L. (Moench.) is a native medicinal plant from North America
used by many Indian tribes for curing toothache and throat pain but also against rabies
and infectious diseases [25]. Herbal products containing Echinacea are one of the most
commonly used in the USA. Echinacea purpurea comprises many chemical compounds,
i.e., water-soluble polysaccharides (arabinoxylan and arabinogalactan types), caffeic acid
derivatives (cichoric, caftaric, and chlorogenic acids), isobutylamides, flavonoids (quercetin
and kaempferol), glycoproteins, essential oils, amines, and polyacetylenes. Due to such
a rich composition, Echinacea shows various activities, i.e., anti-inflammatory, antifun-
gal, antiviral, antibacterial, as well as immunomodulatory. The immunological effect of
Echinacea was analyzed in many studies. Previously, it was demonstrated that in rats
fed with an Echinacea-rich diet, the production of IgA, IgG, and IgM was significantly
increased in comparison to control rats [26]. In turn, in mice treated with Echinacea purpurea,
the splenic lymphocytes were significantly more resistant to apoptosis [27]. Polysaccha-
rides and isobutylamides are responsible for the immunomodulatory effect of Echinacea.
These compounds can activate the immune system’s cells and in turn increase the amount
of leukocytes and the intensity of phagocytosis of macrophages and granulocytes. By
inhibiting the formation of mediators of an inflammatory state, i.e., prostaglandins and
leukotrienes, they also induce secretion of pro- and anti-inflammatory cytokines [28].
Table 1. Characteristics of the studies on the use of cranberries during pregnancy both in animals
and humans.
Experimental Studies
Animal
Reference Treatment Sample Size (N) Adverse Effects Main Results
Species
Significantly (p < 0.05)
larger glomerular diameter
44 mg cranberry in the offspring from
extract/kg cranberry group than in
Mice inbred The morphological
b.m./day, since the control group,
Bałan et al. [19] females of 18 disorder of
copulatory plug, up more CD19+ and CD8+
Balb/c strain the spleen.
to the 28-th day lymphocytes in the
after delivery. cytometry analysis, higher
serum concentration of
VEGF and bFGF.
Human Studies
Cohort
Reference Study Design Treatment Sample Size (N) Adverse Effects Main Results
Allocation
Seven cases of
1st min Apgar
Two cranberry asymptomatic bacteriuria
score < 7 was more
capsules, at a were observed in
A pilot randomized, frequent in the
gestational age of 5 patients: 2 of 24 in the
Wing et al. [20] USA placebo- 33 cranberry group
less than cranberry group and 3 of
controlled study. than in the placebo
16 weeks until 25 in the placebo group.
group (21% vs. 0%,
delivery. There were no cases of
respectively).
cystitis or pyelonephritis.
A total of 39.7% of women
Use of raspberry used herbal drugs during
Herbal medicines
leaves prior to pregnancy, of which 86.3%
Interview using a (most common:
delivery was used conventional drugs.
Nordeng et al. [22] Norway structured ginger, iron-rich 600
associated with an A significant association
questionnaire. herbs, Echinacea,
increased risk of between the use of
and cranberry).
caesarean delivery. iron-rich herbs and
high birthweight.
Cranberry juice cocktail
A total of 27%
A randomized, consumption significantly
cranberry juice
Wing et al. [23] USA controlled pilot 27 None observed. reduced urinary IL-6 in the
cocktail two
investigation. study group compared to
times daily.
placebo group.
Previously, the possible influence of Echinacea purpurea extracts on angiogenic activity

and tissue VEGF and bFGF production of mice fetuses was examined [29]. The authors
demonstrated that Echinacea may interfere with embryonal angiogenesis. Another study
showed that feeding pregnant mice with Echinacea purpurea decreased the number of viable
fetuses [30].
Surprisingly, in a double-blind, placebo-controlled crossover study of 40 healthy males,
the immunologic stimuli of Echinacea purpurea was unconfirmed [31]. The authors did not
observe enhanced phagocytic activity of polymorphonuclear leukocytes or monocytes in
the group of subjects receiving commercially available Echinacea compared to the placebo
group [31]. However, in another study performed in healthy volunteers, it was found that
Echinacea purpurea can inhibit cytochrome CYP1A2 and selectively modulate the catalytic
activity of CYP3A4 at hepatic and intestinal sites [32].
According to the EMA monograph, Echinacea is not recommended in children be-
low 12 years of age due to insufficiently documented safety [33]. Similarly, the use in
pregnancy and lactation is not recommended unless advised by a doctor. The topical
use of Echinacea purpurea is acceptable, omitting the breast area. In contrast, the Ger-
man commission E Monographs indicate no restrictions on the use of Echinacea purpurea
formulations during pregnancy or lactation, with the exception of the parenteral appli-
cation [34]. As with other herbal products, there is also little information on the safety
of using Echinacea purpurea during pregnancy, which is probably safe in recommended
doses [35]. A study conducted in Norway showed no relation between using Echinacea and
risk of developmental defects or adverse side effects in pregnant women [21]. The studies
by Gallo et al. [36,37] showed that the reported use of Echinacea during organogenesis
did not increase the risk of major or minor malformations. Over 200 women using Echi-
nacea products during pregnancy were analyzed and compared to the group of pregnant
women not using Echinacea. Among examined women, 13 spontaneous abortions, 6 major
malformations were observed, while in the control group—7 spontaneous abortions, and
7 major malformations with no statistical differences [37]. According to Perri et al. [35],
oral consumption of Echinacea during the first trimester did not increase the risk for major
malformations and recommended doses of Echinacea were safe during pregnancy and
lactation. Holst et al. [38] identified twenty clinical trials analyzing efficacy of various
Echinacea preparations in different populations. However, for obvious reasons, such trials
are not performed in pregnant women. The findings of selected studies evaluating the
use of Echinacea purpurea during pregnancy both in animals and humans are presented
in Table 2.
Table 2. Characteristics of the studies on the use of Echinacea purpurea during pregnancy both in
animals and humans.
Animal
Species
Significantly (p < 0.05)
larger glomerular
A total of 0.6 mg of Echinacea purpurea extract diameter in the in the
from the 1st day of fertilization until the 18th day offspring from cranberry
of pregnancy. Tablets: Immunal Forte (LEK, The morphological group than in the control
Barcz et al. [29] Mice Ljubljana, Slovenia), Echinapur (Herbapol 18 disorder of group; more CD19+ and
Poznañ, Poznan, Poland) and Esberitox (Schaper the spleen. CD8+ lymphocytes in the
& Brümmer GmbH & Co. KG, cytometry analysis,
Salzgitter, Germany). higher serum
concentration of VEGF
and bFGF.
Human Studies
Cohort
Allocation
Among 68,522 women,
363 (0.5%) reported the
use of Echinacea during
No increased risk pregnancy. There was a
Herbal products
of malformations prevalence of 1.5% of
Heitmann et al. [21] Norway Cohort Study containing Echinacea for 68,522
or adverse effects major malformations
use during pregnancy.
in pregnancy. among the women who
had used Echinacea
compared with 2.6% in
non-users.
A total of 114 (58%) of
A total of 112 women
198 women used capsule
(54%) used Echinacea in
or tablet preparations, or Rates of
the first trimester, with 17
both, of Echinacea malformations
(8%) exposed in all three
(250 to 1000 mg/d) between the study
Gallo et al. [37] Canada A prospective study 206 trimesters. A total of 81%
,76 (38%) of the subjects and control groups
of respondents noticed an
used tinctures did not
improvement in the
(5 to 30 drops per day). significantly differ.
symptoms of upper
Duration of use:
respiratory tract ailments.
5 to 7 days.
3.3. Garlic (Allium sativum)

Garlic contains several sulfur-containing compounds such as alliin, diallylsulfides, and al-
licin, which show antimicrobial activity, especially against Escherichia coli, Staphylococcus aureus,
and Escherichia faecalis, but also against Candida spp. and Trichomonas vaginalis [39,40]. It
was also suggested that use of garlic may prevent group B Streptococcus (GBS) disease in
newborns and in consequence may decrease the costs of the antibiotics which are admin-
istered during the labor [41]. Garlic may reduce oxidative stress and blood pressure as
well as inhibit platelet aggregation, which suggests its role in prevention of pre-eclampsia.
However, the available data in the topic are often contradictory [42,43].
In animal model, garlic (administered with a dose of 100 mg/kg body weight (bw) for
three weeks) was found to influence the amelioration of lipid parameters of both pregnant
Wistar dams and their offspring as a result of its antioxidant activity [44]. Significant effects
of garlic and ascorbic acid, administered to pregnant Wistar rats, in reduction of lead
level in blood and brain were also shown [45]. The findings suggested that garlic may
protect against lead-induced neuronal cell apoptosis in the developing hippocampus of rat
pups [45]. The beneficial effects of this natural antioxidant in protecting against lead toxicity
were also noted in other studies [46,47]. Co-administration of lead (at a dose of 160 and
320 mg/kg bw) with garlic extract (250 mg/kg bw) to pregnant rats resulted in reductions
in lead levels not only in the mother’s blood but also in the cerebellum, placenta, and fetal
brain [47]. In immunohistochemical staining, a reduction in the number of Purkinje cells
in the cerebellum was observed in the group of animals exposed to lead. Additionally,
degenerating pyknotic cells and vacuolization in the Purkinje cell layer were found. Garlic
treatment attenuated the histopathological changes caused by lead administration in both
the female and fetal cerebellum.
According to the results by Hsu et al. [48], garlic oil supplementation during pregnancy
and lactation protects adult rat offspring against hypertension induced by perinatal high-
fat diet. Garlic oil, as a precursor of H2S, was shown to increase the mRNA expression
and activity of H2S-producing enzymes in the kidneys of offspring. Furthermore, it was
observed that garlic oil therapy resulted in stimulation of Lactobacillus and Bifidobacterium
growth and decrease of Turicibacter and Staphylococcus genera in the gut microbiota [48].
The results of a randomized, double-blind, placebo-controlled trial conducted in
44 pregnant women showed decreased levels of serum C-reactive protein and increased
plasma glutathione in women obtaining 400 mg garlic in one tablet for 9 weeks compared
to the placebo group [49]. In a large cohort of pregnant Norwegian women, garlic was
demonstrated to decrease the risk of spontaneous preterm delivery, which may result from
microbial infection during pregnancy [50].
A Saudi study demonstrated that 56% of the 297 pregnant women surveyed used
herbal medicine, and 15.4% of them used garlic and 13.4% ginger [51]. Most women (i.e.,
82%) relied on informal sources to use herbal supplements during pregnancy [51]. Garlic,
together with ginger, was previously found to be the most frequently used herbal product
by pregnant women from Ethiopia [6,52–54]. Comparatively, a study based on 350 women
from the West Bank of Palestine demonstrated that 77.1% of them were taking herbs
during pregnancy and lactation [55]. The survey results showed that the most commonly
used plants during pregnancy were peppermint, sage, and anise, while during lactation:
cinnamon, anise, peppermint, and sage. On the other hand, garlic was not used because
it changes the smell of breast milk. The authors also showed that sometimes there were
differences between the traditional and scientific uses of herbal remedies by the women
surveyed [55]. The results of selected studies regarding the use of garlic during pregnancy,
both in animals and humans, are presented in Table 3.
Table 3. Characteristics of the studies analyzing the use of garlic during pregnancy both in animals and humans.
Reference Animal Species Treatment Sample Size (N) Adverse Effects Main Results
Allium sativum supplementation to
hypercholesterolemic pregnant rat
decreased the incidence of abortion
A total of 100 mg homogenate of garlic/kg bw for
and abnormalities of the newborn,
El-Sayyad et al. [44] Rats three weeks prior to onset of gestation as well as 60 Not mentioned
improved ossification, and
throughout the gestation period.
ameliorated the histological picture
of myocardial muscle fiber of
their offspring.
Significantly reduced blood and
Lead-treated group: lead acetate in the brain lead levels in young rats in the
drinking water (1500 ppm) Lead + Garlic group (p < 0.01)
Lead plus Garlic-treated group: to lead acetate in compared to lead-treated animals
Ebrahimzadeh- Rats Not mentioned
50 Significant decrease in the number
Bideskan et al. [45] the drinking water (1500 ppm) + 1 mL Garlic
juice (daily dose of 100 g/kg bw by gavage of apoptotic cells in all subregions
during pregnancy and lactation. of the hippocampus (p < 0.05) in the
Lead plus Garlic-treated group vs.
in the lead-treated group.
Immunohistochemical examination
of the cerebellar cortex of rats in the
low dose Pb-treated group showed
irregular arrangement and wide
Two Pb-treated groups (exposed to 160 and
separation between Purkinje cells
320 mg/kg bw of Pb, respectively).
and in high dose Pb-treated group,
Two groups treated with both Pb and garlic
Saleh et al. [47] Rats 40 Not mentioned a decrease in the number of
(exposed to Pb as previous groups together with
Purkinje cells was evident.
250 mg/kg bw/day of garlic extract). Treatments:
Simultaneous administration of
once a day from GD 1–20 of pregnancy.
garlic extract + Pb resulted in a
significant reduction in Pb levels in
maternal blood and brain, placenta,
and placental and fetal brain.
Table 3. Cont.
Maternal garlic oil therapy:

Pregnant rats received either a normal diet (ND) - Prevented high-fat diet-induced
or 58% high-fat diet. Garlic oil (GO) or vehicle hypertension in adult rat offspring;
was administered daily at 100 mg kg−1 day−1 - Increased mRNA and activity of
Hsu et al. [48] Rats during pregnancy and lactation. Male offspring 32 Not mentioned H2S-producing enzymes in
were fed with the same diet as their dams until offspring’s kidneys;
16 weeks. Experimental groups (N = 8/group): - Increased growth stimulation of
ND, HF, ND + GO, and HF + GO. the Lactobacillus and
Bifidobacterium.
Human Studies
Reference Cohort Allocation Study Design Treatment Sample Size (N) Adverse Effects Main Results
No significant difference between
Two tablets of garlic
the two groups in the means of
(800 mg/day) during
HDL, LDL, triglyceride, systolic and
the third trimester
Randomized, diastolic blood pressure, inhibition
of pregnancy for
Ziaei et al. [43] Iran single-blind, 100 Not mentioned of platelet aggregation, and the
8 weeks. Each garlic
placebo-controlled study. mean arterial blood pressure.
tablet contained
Significant difference in the means
1000 µg allicin,
of total cholesterol (p = 0.038) and
and ajoene.
hypertension alone (p = 0.043).
A significant decrease in the level of
high sensitivity CRP (p = 0.01) and
Participants received an increase in the concentration of
Randomized, one garlic tablet No serious glutathione (GSH) in the
Aalami-Harandi et al. [49] Iran double-blind, (400 mg garlic and 44 adverse reactions plasma (p = 0.03).
placebo-controlled trial. 1 mg allicin) once were reported. Serum lipid profiles, plasma total
daily for 9 weeks. antioxidant capacity (TAC) levels,
and pregnancy outcomes are similar
in both groups.
Table 3. Cont.
Out of 18,888 deliveries, 950 (5.0%)

Alliums (garlic,
spontaneous preterm
onion, leek, and
deliveries were found.
spring onion) intake
Population-based Garlic intake significantly reduces
Myhre et al. [50] Norway Garlic usage was 18,888 Not mentioned
pregnancy cohort study. the risk of both early (OR: 0.47 (95%
classified as: low
CI: 0.25; 0.89)) and late (OR: 0.83
intake: ≤0.40 g and
(95% CI: 0.71, 0.98)) spontaneous
high intake: >0.40 g.
preterm delivery.
4. Herbal Medicines Used to Counteract Some Pregnancy-Related Symptoms (e.g.,

Nausea and Vomiting, Dizziness and Headache, and Memory Loss)
4.1. Chamomile (Matricaria chamomilla L.)
Chamomile belongs to the Asteraceae family. For centuries, it was traditionally
used to treat wounds, ulcers, eczema, or skin irritations, but also in the management of
neuralgia, rheumatic pain, and eyes disorders. There are two different chamomile plants:
German chamomile and Roman chamomile. The common German variety comes from
the flower of Matricaria recutita, while the less common Roman variety comes from the
flower of Chamaemelum nobile. The benefits of using chamomile are due to the fact that the
essential oils and flower extracts derived from chamomile contain more than 120 chemical
components, many of which are pharmacologically active. They include, among others:
sesquiterpenes (e.g., bisabolol and farnesene), sesquiterpenelactones (e.g., chamazulene
and matricin), flavonoids (e.g., apigenin and luteolin), and volatile oils [56–58]. Studies
have shown that chamomile may be used as a mild digestive relaxant to treat, among
others, indigestion, motion sickness, nausea, and vomiting [59].
Modares et al. [60] conducted a randomized, placebo-controlled, triple-blind study,
which was based on 105 pregnant women with mild to moderate vomiting and nausea.
Participants took 500 mg ginger root powder, or 500 mg dried German chamomile flower
or starch capsules (500 mg, placebo group) for 1 week. The authors observed that Rhodes
index score (vomiting and depressed reflexes) in the chamomile group was significantly
lower than in the placebo group (p < 0.05) [60].
Chamomile was reported to be one of the most common herbs used by pregnant women
from north-east Italy [61]. A total of 44% of analyzed women used it through oral or topical
route to counteract anxiety, digestive problems, and stretch marks. The authors observed
that 21.6% of regular users of chamomile during pregnancy showed higher frequency of
threatening miscarriages and preterm labors compared to non-users [61]. In addition, in
two neonates after a regular maternal consumption of chamomile, a cardiac malformation
(presumably related to Down syndrome), and an enlarged kidney were diagnosed.
On the other hand, no effect of chamomile use during the last two trimesters on
premature birth was reported in a large Canadian population-based study [62]. The authors
observed similar frequency of women using chamomile in both a group who had premature
delivery and in a term delivery group.
In Pakistan, chamomile is used by traditional birth attendants to relieve labor pain.
However, a study by Zafar et al. [63] found no significant difference in pain relief during
labor between women using Chamomile and women receiving Pentazocine. An Iranian
study analyzed the effectiveness of chamomile in inducing labor in women with a gesta-
tional age of 40 weeks or more, cephalic presentation, an absence of uterine contraction, as
well as a cervical Bishop score of less than four [64]. Women in the study group received
capsules with chamomile extract (500 mg) for 7 days (6 capsules a day). The authors
observed that the onset of labor was significantly faster (p = 0.003) in the chamomile group
than in the placebo group [65]. In another study, Heidari-Fard et al. [65] applied chamomile
aromatherapy to women in labor at 4 cm dilatation and continued it until the end of de-
livery. It has been shown that the chemocline odor significantly reduces the intensity of
contractions in dilatation of 5–7 cm in the chamomile group compared to the control group.
A study by Silva et al. [66] reported a case of a 29-year-old Caucasian Portuguese
woman who noticed an abundant amount of milk and breast enlargement 4–6 h after
drinking chamomile tea. From 3 to 6 months after delivery, the patient drank about 1.5 to
2 liters of chamomile infusion a day. As the analyzed woman observed, her milk production
increased from about 60 mL to about 90 mL during this time. Although the mechanism
of chamomile’s galactogogue effect remains unclear, it has been assumed that chamomile
may elicit its estrogenic activity by inhibition of CYP 1A1, 1A2, and 3A4 by its bioactive
compounds such as apigenin, luteolin, quercetin, and caffeic acid [67,68].
Table 4 shows the results of selected studies analyzing the usage of chamomile during
pregnancy, both in animals and humans.
Table 4. Characteristics of the studies on the use of chamomile during pregnancy in humans.
Human Studies
Cohort
Allocation
1st group: ginger
capsules (500 mg ginger No significant difference
root powder) Chamomile between chamomile and
Triple-blind 2nd group: chamomile group: ginger after one week
randomized capsules (500 mg dried skin allergy, of treatment.
Moderes et al. [60] Iran 105
placebo- chamomile flower) ginger group: Significant difference
controlled trial. 3rd group: starch diarrhea between chamomile and
capsules (500 mg, and vomiting. placebo after one week
placebo) twice a day for of treatment.
one week.
Anesthesia of the
woman in the early stage
of labor (3–6 cm):
- Conventional group:
No significant
intramuscular injection
differences in pain were
Double blind of Pentazocine
noticed between three
Zafar et al. [63] Pakistan randomized (30 mg/mL); 99 Not mentioned
groups (Chamomile,
controlled trial. - Homeopathy group:
Pentazocine, and
three drops of 1 M
placebo).
solution chamomile;
- Placebo group:
dispensed of
sugar pellets.
A total of two capsules Gestational age at the
every 8 h for 7 days time of delivery in the
Double-blind
Gholami et al. [64] Iran (1 capsule 80 Not mentioned chamomile group was
clinical trial study.
contained 500 mg significantly shorter than
chamomile extract). the placebo group.
A total of two drops of Duration of contractions
chamomile essence was and number of
added to a gauze. contractions of the first
Aromatherapy started delivery were similar in
during dilatation of 4 cm chamomile and control
Randomized and continued to the groups. In dilatation of
Heidari-Fard et al. [65] Iran 130 Not mentioned
clinical trial. end of delivery. 5–7 cm, intensity of
Use of the essence was contractions in the
repeated every half an intervention group was
hour for three times in significantly (p = 0.004)
the range of determined lower than the
dilatations. control group.
4.2. Ginger (Zingiber officinale Rosc.)

Rhizome is a therapeutic part of ginger (Zingiberis Rhizoma). It contains two active
complexes: Gingerol, a phenolic compound giving a sharp taste, and Shogaol [69]. Gingerol
shows antiemetic activity and Shogaol acts as a 5-HT antagonist on serotonin receptors in
the ileum. Other active compounds of ginger are as follows: non-volatile substances (resins),
essential oil (e.g., aromatic hydrocarbons sesquiterpenes, zingiberen, kurkumen, and β-
bisabolen), as well as lipids and glycolipids [70]. Ginger works through many interesting
mechanisms, i.e., increases gastrointestinal transport with the effects characteristic to
prokinetic antiemetic drugs [71], and in consequence ingested food has less time to cause
upper gastrointestinal problems such as vomiting. Ginger also suppresses vasopressin,
which may cause nausea in high levels, and inhibits stomach activity, which can also result
in nausea [69]. The anticoagulant effect of ginger and the interactions between ginger and
anticoagulant drugs were also observed [72], suggesting its complete avoidance during the
anticoagulant therapy. However, Jiang et al. [73] found no effect of ginkgo and ginger on
pharmacokinetic and pharmacodynamics of warfarin in 12 healthy male subjects as well as
no effect on blood clotting status or platelet aggregation. Ginger is “generally regarded as
safe” by the Food and Drug Administration (FDA) in the United States. On the other hand,
in Finland, the Finnish Food Safety Authority does not recommend ginger products (i.e.,
tea or food supplements containing ginger) during pregnancy due to the lack of known safe
consumption limits [74]. Ginger is used most commonly to relieve nausea and vomiting
during the first trimester of the pregnancy.
In animal model, no maternal and developmental toxicity was observed after adminis-
tration of zingiber extract at daily doses of up to 1000 mg/kg bw to the pregnant rats (6 to
15 days of gestation) [75]. The study by ElMazoudy and Attia demonstrated that ginger at
doses of 1000 and 2000 mg/kg bw/day caused maternal toxicity, with increased mortality
and a significant decrease in body weight gain in female mice [76]. The authors also showed
that a dose of 2000 mg/kg in females significantly reduced the number of live fetuses and
increased fetal death and resorption, but no adverse effects were observed for the doses of
250 and 500 mg/kg. The daily administration of ginger extract (at a dose of 200 mg/kg bw)
to pregnant rats during the organogenesis phase of gestation, i.e., from 6th to 15th day of
gestation, 1 h after gabapentin injection, minimized the brain damage in rat fetuses caused
by this antiepileptic drug [77]. In addition, the immuno-histochemical investigation found
that co-administration of ginger after gabapentin injection resulted in a significant decrease
in the expression of the pro-apoptotic marker Caspase-3 and an increase in the expression
of the anti-apoptotic marker Bcl-2 in fetal rat brains. Another study by El-Borm et al. [78]
showed that ginger extract (200 mg/kg) significantly ameliorated the pathological changes
in fetal cardiac tissue induced by labetalol, a drug used to treat maternal hypertension
during pregnancy.
Ginger is undoubtedly the most analyzed herbal remedy used in pregnancy. Most
recently, a Swiss cross-sectional survey, comparing the usage of herbal medicines during
pregnancy in women with and without mental disorders or symptoms (MDS), showed that
among 272 respondents, the ginger (49.2%), raspberry leaf (42.7%), bryophyllum (37.8%),
chamomile (27.2%), lavender (22%), and iron-rich herbs (12.3%) were the most frequently
taken herbal medicines [79]. The vast majority of pregnant women participating in the
study rarely chose synthetic psychoactive medications for the treatment of MDS, but were
more likely to use pharmaceutical herbal products (valerian, lavender, and bryophyllum).
The Canadian study demonstrated that women who used ginger against nausea and
vomiting found it only moderately effective [80]. However, meta-analysis performed on a
large group of almost 1300 pregnant women showed that ginger significantly improved the
symptoms of nausea and showed some improvement in reducing the number of vomiting
episodes compared to the placebo group [81]. The effectiveness of ginger in relieving nau-
sea and vomiting was also compared to vitamin B6 in the study by Sharifzadeh et al. [82].
A total of three groups of pregnant women between 6 and 16 weeks of pregnancy were
administered with ginger, vitamin B6, and placebo, respectively. The authors found that
ginger is comparable with vitamin B6 in the treatment of mild to moderate nausea and
vomiting during pregnancy as well as being more effective than the placebo [82]. Inter-
estingly, in the study by Smith et al. [83], the frequency of spontaneous abortions was
lower in the group of women who were ingesting ginger compared to those ingesting
vitamin B6. On the other hand, in the double-blind, randomized, placebo-controlled trial
by Willetts et al. [84], 120 women in less than 20 weeks pregnant randomly received wax
sealed capsules containing 125 mg of ginger extract or soya bean as placebo. The authors
observed that the nausea experience score was significantly lower for the ginger extract
group than in the placebo group, while no significant effect was observed on vomiting.
In turn, in the case of hyperemesis gravidarum, a double-blind, randomized trial showed
that ginger significantly (p = 0.035) relieved symptoms in women receiving 1 g of ginger
compared to pregnant women receiving placebo [85].
Tianthong and Phupong [86] investigated in a randomized, double-blind, placebo-
controlled trial the efficacy of ginger capsules in the prevention of abdominal distention in
89 post cesarean section women. They demonstrated that the incidence of postoperative
abdominal distention was not different between the ginger and the placebo groups, but the
severity of abdominal distention on the fourth day after operation was significantly lower
in the ginger group than the placebo group. In the ginger group, the number of women
who could eat in this condition was higher than in the placebo group (59.6% vs. 43.8%,
p = 0.035). In addition, defecation was faster in the ginger group.
Hajimoosayi et al. [87] reported that ginger tablets taken for 6 weeks by women with
gestational diabetes mellitus with impaired glucose tolerance test significantly reduced
fast blood glucose, serum insulin, and Homeostasis Model Assessment index compared
to the placebo group. In addition, there was no significant reduction of the serum blood
glucose 2 h post-prandial in both groups, which, according to the authors, could be due to
the use of the same diet in both groups. However, ginger intake was related to a shorter
gestational age as well as to a lower circumference of the newborn’s skull in Italian pregnant
women compared to those who did not use ginger [11]. A cross-sectional study conducted
among women in early pregnancy or postpartum women from Scotland identified eight
herbal products (aloe, chamomile, cranberry, fish oil, ginger, ginseng, grapefruit, and sage)
that may cause interactions with concomitant prescription drugs [88]. Of the 34 potential
interactions, one between ginger and nifedipine was reported as potentially major.
Ginger was also observed to enlarge milk production after delivery. Women from
Thailand receiving 500 mg dried ginger capsules twice daily have significantly higher
milk volume than the placebo group (191.0 ± 71.2 mL/day and 135.0 ± 61.5 mL/day,
respectively) [89]. However, the authors demonstrated that the seventh day milk vol-
ume in women taking ginger capsules did not differ from the milk in women from the
placebo group.
The results of selected studies regarding the use of ginger during pregnancy, both in
animals and humans, are presented in Table 5.
4.3. Gingko biloba L.

Ginkgo biloba L. is a tree belonging to the ginseng family which originated from south-
east regions of China. Extracts from Ginkgo biloba are one of most widely used as well as best
studied herbal products. These complex mixtures contain numerous components, mostly
including flavonoids (e.g., quercetin) and terpene lactones and in addition bioflavonoids,
ginkgolic acids, and ginkgotoxin, showing a vitamin B6-similar structure [90,91]. The
Ginkgo biloba extract has many advantages but when applied at high doses it may be toxic to
the cells, i.e., it may increase human red blood cells fragility, influence cellular morphology,
and induce glutathione consumption [92]. Ginkgo has no specific uses during pregnancy
or breastfeeding; however, it may be a component of herbal mixtures or teas. It may be
commonly used as an antioxidant or a vasodilator to increase cerebral and peripheral
perfusion. The most obvious reason of usage of Ginkgo is to improve memory but also to
manage headaches.
In 2016, extract from leaves of Ginkgo biloba was classified as a possible human car-
cinogen (Group 2B) by the International Agency for Research on Cancer [93]. Previously,
Ginkgo biloba extract was demonstrated to indicate carcinogenic activity in mice due to
increased incidence of hepatocellular carcinoma and hepatoblastoma [94].
Table 5. Characteristics of the studies analyzing the use of ginger during pregnancy both in animals and humans.
EV.EXT 33, a patented Zingiber officinale extract
1st group: 100 mg/kg On day 21 of pregnancy, for a
2nd group: 333 mg/kg dose of 1000 mg/kg, no
No deaths or adverse
Weidner et al. [75] Rats 3rd group: 1000 mg/kg 22 adverse effects for both
reactions were observed
Placebo: sesame oil maternal and developmental
Treatment: by oral gavage from days 6 to toxicity were observed.
15 of gestation.
Mice treated with 2000 mg/kg
bw/day displayed significant
Doses of 1000 and decreases in implantation sites.
Mice received ginger orally at 0, 250, 500, 25 female mice/group 2000 mg/kg bw/day In this dose, ginger impaired
ElMazoudy et al. [76] Mice
1000 or 2000 mg/kg bw/day. (125 mice in total) resulted in the normal growth of corpus
maternal toxicity luteum because of
progesterone insufficiency
during early pregnancy.
1st control group: 1 mL distilled
water, intraperitoneally. Co-administration of
2nd ginger group: 200 mg/kg, per os gabapentin (GBP) with ginger
24 pregnant rats,
Badawy et al. [77] Rats 3rd GBP group: 162 mg/kg intraperitoneal injection Not mentioned during pregnancy reduces the
36 fetuses
4th GBP + ginger group: intraperitoneal injection of neurotoxicity of the
GBP first followed by oral administration of ginger antiepileptic drug.
1 h later. Treatment: from days 6 to 15 of gestation.
Co-administration of ginger
1st control group: distilled water
extract with labetalol during
2nd ginger group: 200 mg/kg,
pregnancy significantly
3rd labetalol group: 300 mg/kg
ameliorated labetalol-induced
El-Borm et al. [78] Rats 4th labetalol + ginger group: oral injection of 60 Not mentioned
apoptosis as well as DNA
labetalol first followed by oral administration of
damage, histological and
ginger 1 h later. Treatment: from days
ultrastructural changes in the
6 to 15 of gestation.
cardiac tissue of rat fetuses.
Table 5. Cont.
Human Studies
Out of 398 women, 272 used
pharmaceutical herbal
products, including ginger
(49.2%), raspberry leaf (42.7%),
bryophyte (37.8%), chamomile
(27.2%), lavender (22%), and
Pharmaceutical herbal
iron-rich herbs (12.3%).
preparations for mild
Gantner et al. [79] Switzerland Cross-sectional survey. 398 Well tolerability. In the treatment of Mild
MDS treatment
Mental Disorders (MDS),
during pregnancy.
pregnant women were more
likely to choose herbal
(mainly: St. John’s wort, hops,
valerian, lavender, and
bryophytes) than
synthetic medications
Of 27 women, 10 used herbal
products to counteract nausea
Semi-structured
Westfall et al. [80] Canada Doses were not specified. 27 Not mentioned. and vomiting. Moderate
interviews.
reduction in nausea and
vomiting was observed.
Nausea: significantly
Ginger intervention:
reduces the number of nausea
fresh root, dried root, Not pose a risk for
episodes (MD 1.20, 95% CI
Randomized powder, tablets, capsules, side-effects or adverse
Viljoen et al. [81] South Africa 1278 0.56–1.84, p = 0.0002)
controlled trials. liquid extract, and tea. events during
compared to placebo.
Dose from 600 to pregnancy.
Vomiting: no significant
2500 mg ginger/day.
difference between the groups.
Table 5. Cont.
1st group: ginger capsules

(500 mg)
Ginger and vitamin B6 are more
2nd group: vitamin B6 Ginger showed no
Triple-blind effective than placebo in
Sharifzadeh et al. [82] Iran capsules (40 mg) 77 adverse effects on
clinical trial. reducing NVP (p = 0.039 and
Treatment: twice daily for pregnancy outcome.
p = 0.007, respectively).
4 days between 6 and 16
weeks of pregnancy.
Ginger was equivalent to
vitamin B6 in reducing nausea
(mean difference 0.2, 90%
Randomized, 0.5 g of ginger or 75 mg of Women taking ginger
confidence interval (CI) −0.3,
Smith et al. [83] Australia controlled vitamin B6 daily for 291 reporting belching
0.8), retching (mean difference
equivalence trial. 3 weeks. after ingestion.
0.3; 90% CI −0.0, 0.6), and
vomiting (mean difference 0.5;
90% CI 0.0, 0.9).
The nausea experience score
was significantly lower for the
- the active treatment:
women taking ginger extract
125 mg ginger extract
Randomized, after the first day of treatment
(equivalent to 1.5 g of No adverse effects
Willetts et al. [84] Australia controlled 120 and this difference was present
dried ginger) were observed.
equivalence trial. for each treatment day than for
- the placebo: soya bean oil
women from placebo group. No
four times a day.
significant effect was observed
on vomiting.
1st group: ginger capsules
(250 mg of powdered
root ginger)
2nd group: placebo Mean relief scores highlighted
Double-blind,
capsules (250 mg No side effects greater relief of symptoms after
Fischer-Rasmussen et al. [85] Denmark randomized, 30
of lactose) were observed. ginger treatment compared to
cross-over trial.
Treatment: four times placebo (p = 0.035).
daily for 4 days, followed
by a 2-day wash out before
alternate treatment
Table 5. Cont.
Statistically significant
differences in the levels of Fast
Randomized, Blood Sugar (p = 0.04), serum
Three tablets of ginger
double-blind, insulin (p = 0.01), and
Hajimoosayi et al. [87] Iran (1500 mg)/day, for 70 Not mentioned.
placebo-controlled Homeostasis Model
six weeks.
clinical trial. Assessment index (p = 0.05)
compared to the
placebo group.
A total of 81% of women
consistently used at least one
The most commonly
Ginger intake resulted in herbal product throughout
used herbal products
a shorter gestational age their pregnancy.
Retrospective were chamomile, fennel,
Trabace et al. [11] Italy 600 and a smaller head The most commonly used
observational study. propolis, cranberry,
circumference herbal products were
lemon balm, ginger,
of newborns chamomile, fennel, propolis,
valerian, and mallow.
cranberry, lemon balm, ginger,
valerian, and mallow.
A total of 44.9% of pregnant
women ingested prescription
Potentially major drugs simultaneously with at
interactions: least one herbal and natural
Participants used
ginger–nifedipine. products. Of this group, 12.7%
prescribed medicines, or
McLay et al. [88] United Kingdom Cross-sectional survey. 889 Moderate interactions: of the women had
herbal or natural
ginger–metformin 34 moderate herbal drug
products, or both.
ginger–insulin interactions, one assessed as
ginger–aspirin. potentially major (ginger and
nifedipine) and one as minor
(ondansetron and chamomile).
In animal models, the possible impact of Ginkgo biloba extract on fetus is well docu-
mented. No toxic effect on the Wistar dams and no fetal malformations were observed
after using Ginkgo biloba extract [95]. However, earlier Ginkgo biloba was found to have
reproductive toxicity in the mouse model. Zehra et al. [96] observed that fetuses from
mice who received higher doses of Ginkgo extract (i.e., 100 mg/kg/day) showed increased
frequency of malformations including round shaped eye and orbits, syndactyly, and mal-
formed pinnae, nostrils, lips, and jaws. The study concerning possible effects of 6-gingerol
from Ginger, Ginkgolide A, and Ginkgolide B from Gingko biloba and Ginsenoside Rg1 from
Ginseng was performed in the chick embryonic heart micromass and Mouse D3 embryonic
stem cells with analysis of the following cell aspects: alteration in contractility, cell viability,
and cell protein content [97]. The results showed that herbs used in the first trimester
of pregnancy might not be safe for fetal development. Ginkgo biloba extract may show
a neurotrophic effect, which was demonstrated in fetuses of pregnant rats administered
with 100 or 300 mg/kg/day Ginkgo biloba extract for 5 days [98]. The increased number of
hippocampal neurons as well as altered expression of 160 or 187 genes in the hippocampi
of female or male fetuses, respectively, were observed in this study [98].
Chen et al. [99] analyzed a perinatal hypoxic-ischemic on neonatal male rats. In the
study, it was observed that administration of Ginkgolide B 30 minutes before ischemia
induction resulted in a decrease in the level of interleukin (IL-1β and IL-18) and inhibition
of NLRP3 inflammasome activation, which corresponded to a reduced infarct volume and
an alleviation of cerebral edema in the study group.
Data on the usage of Ginkgo extract during pregnancy in women are scarce. A study
by Holst et al. [100] identified Ginkgo as one of the herbs used by Swedish women dur-
ing pregnancy, mostly to improve circulation and cognitive functioning. The study by
Petty et al. [101] demonstrated correlation between the use of herbal supplements and the
appearance of colchicine in placental blood. Significant levels of colchicine (3 µg/tablet)
were found by the authors in the commercially available Ginkgo biloba formulations [101].
Colchicine shows anti-inflammatory, anti-metastatic, and teratogenic activities, which were
previously found to be fatal in high doses [102]. However, data from Israel did not report
colchicine as a human teratogen because the rate of major congenital anomalies was com-
parable between the pregnancies exposed on colchicine and those who were not exposed.
Furthermore, no cytogenetic anomalies were observed in the colchicine group [103]. Ginkgo
should be avoided especially around labor because it could prolong bleeding time due
to its possible anti-platelet properties. Table 6 demonstrates characteristics and findings
of selected studies regarding the use of Ginkgo biloba during pregnancy, both in animals
and humans.
4.4. Peppermint (Mentha piperita)

Peppermint leaves and oil contain, among others: menthol (35–45%), menthone, men-
thyl acetate, neomenthol, isomenthone, limonene, rosmaric acid, and flavonoids [104]. It
shows a spasmolytic effect on the smooth muscle of the digestive tract but also antiviral,
antimicrobial, or diuretic activities [105–109]. Both peppermint oil and menthol can posi-
tively affect nausea and vomiting by acting on the 5-HT(3) receptor ion–channel complex,
probably by binding to a modulatory site, which is different from the site of serotonin
binding [110]. According to Hines et al. [111], inhalation aromatherapy with peppermint
compared to placebo may cause little or no difference in the severity of postoperative
nausea and vomiting. Postoperative nausea and vomiting are common postoperative
complications, the causes of which may include anesthesia, anxiety, and stress [112]. In a
single-blind, randomized, controlled trial, it was shown that inhalation of 0.2 mL of 10%
and 30% peppermint essential oil in each of the study groups significantly reduced the
severity of nausea after the intervention [112]. In many clinical trials, inhalation of pepper-
mint oil has been shown as effective in reducing the perceived severity of postoperative
nausea and, according to the authors, should be considered as a first-line treatment that
can be used quickly [113–117]. In addition, peppermint oil aromatherapy offers a rapid
onset of action, ease of administration, and the absence of any serious side effects [118].
Table 6. Characteristics of the studies analyzing the use of Ginkgo biloba during pregnancy both in
animals and humans.
Animal
Species
There was no significant
difference between the
number of live and dead
fetuses, average fetal
Extract of Ginkgo bilboa in concentrations
weight/offspring, and
Fernandes et al. [95] Rats of 3.5, 7.0, and 14.0 mg/kg/day, from the 64 Not observed.
average placenta
1st to the 8th day of pregnancy.
weight/offspring
between experimental
groups and
control group.
In the group receiving
Fetuses from groups
100 mg/kg/day,
78 mg/kg/day did not
reduced body weight
show any gross
Ginkgo biloba extract 78, 100 mg/kg/day and malformations were
Zehra et al. [96] Mice 18 abnormalities.
throughout the gestational period. observed: round shape
Not allowed in
of the eye and orbits,
pregnancy, even for
malformed pinnae,
nutritional value.
nostrils, lips and jaws.
Human Studies
Cohort
Allocation
The mother’s use of the
examined herbal drugs
was not significantly
associated with any Among 787 using herbal
Herbal drugs negative effects for the drugs during early
reported used by infant. According to the pregnancy, four (0.5%)
Registry-based
Holst et al. [100] Sweden Swedish women 787 authors, too low a reported usage
study.
during early number of exposures Ginkgo biloba to improve
pregnancy. does not allow to circulation and
exclude the influence of cognitive function.
herbal drugs on rare
outcomes e.g., specific
malformations.
Peppermint is often used to relieve nausea and vomiting in pregnancy. Experimental

studies showed that peppermint may not have any teratogenic effect in mice fetuses [119].
The authors demonstrated that when using hydroalcoholic extract of Mentha piperita at doses
600 and 1200 mg/kg/day continuously during embryonic period, no serious congenital
malformations or delayed bone ossification were found in the fetuses [119].
Several studies regarding the impact of peppermint on pregnancy in women were
previously published [120–128]. Many studies pointed to the possibility of using aro-
matherapy, one of the types of complementary medicine, as a care option for pregnant
women to minimize nausea and vomiting in early pregnancy. In this regard, a randomized
clinical trial involving 90 pregnant women showed a significant reduction in the severity
of nausea and vomiting on the second, third, and fourth days of inhalation aromatherapy
with lemon and peppermint in the study group compared with baseline assessment, before
the intervention [120]. The study by Joulaeerada et al. [121] showed that inhalation with
peppermint oils by pregnant women decreased the severity of nausea and vomiting, but
this reduction was not statistically significant compared to the placebo group, which used
sweet almond oil. Similar effects of inhalation aromatherapy with peppermint essential oil
treatment were reported by Pasha et al. [122]. They observed that the intensity of nausea
and vomiting in the peppermint aromatherapy group was higher than in the saline group,
but it was not significant.
In turn, peppermint oil was observed to be effective in reducing the severity of
pruritus, which concerns up to 8% of pregnant women [123]. Menthol, the main peppermint
component, decreases itching caused by histamine by cooling the skin. However, when
used in an excessive way, it may induce uterine bleeding in early pregnancy [123]. In
the study by Kıssal et al. [124], peppermint was found to be commonly used against
cold-influenza in 1st and 2nd trimesters of pregnancy.
In the literature, peppermint used in normal doses has been classified as safe for
pregnant women [125]. Study results from eight cross-sectional studies (2729 participants)
from seven Asian countries showed that approximately 47% of women had used at least
one herbal medicine during a previous pregnancy. Of the 33 herbs, peppermint was men-
tioned the most (22.8% of women) [125]. In addition, a cross-sectional study of 320 Iranian
women found that 48.4% of them used herbal medicines during pregnancy, of which sour
orange (30.97%), peppermint (19.81%), and borage (19.46%) were the most commonly indi-
cated [126]. Pregnant women with secondary education and from higher socio-economic
classes were more likely to use herbs.
Amzajerdi et al. [127] observed in pregnant women that after 7 days of using the
mint flavor, the mean score of nausea and vomiting in the study group was significantly
lower than in the control group, although in both groups on the last day of the interven-
tion, the mean score of nausea and vomiting decreased significantly. In another study,
Ghani et al. [128] observed a significant decrease in nausea and vomiting episodes on the
third day of mixed essential oils (peppermint and lavender) inhalation in early pregnancy.
In turn, a Canadian study found that peppermint was not related to the preterm
delivery [62]. The authors observed comparable frequency of women using peppermint
during the whole pregnancy in the group of over 600 women who delivered before 37 weeks
of gestation as in the group of over 2500 women with term delivery (2.09% vs. 1.79%,
respectively). The summary of the main findings of selected studies evaluating the use of
peppermint during pregnancy both in animals and humans is demonstrated in Table 7.
Table 7. Characteristics of the studies analyzing the use of peppermint during pregnancy, both in
animals and humans.
Two experimental groups receiving 600 mg/kg/day and 1200

mg/kg/day orally of Mentha piperita extract and two control No signs of maternal
A total of 12 mice in
Golalipour et al. [119] Balb/c Mice groups: one control group received normal saline orally by Not observed. toxicity due to Mentha
experimental groups.
oral intubation. The other control group did not receive piperita treatment.
normal saline.
Human Studies
Inhalation with three drops Nausea and vomiting

of a solution containing 5% scores; significantly greater
Double-blind, randomized lemon essential oil and 5% No side effects have on the second, third, and
Safajou et al. [120] Iran 90
clinical trial. mint essential oil when been reported. fourth days of intervention
feeling nauseous for 4 days in peppermint and lemon
of treatment. group vs. in placebo group.
Before and during the

four-day intervention
Inhalation aromatherapy period mean scores of NVP
Joulaeerad et al. [121] Iran Single-blind clinical trial. with 10% peppermint 56 Not mentioned. significantly decreased in
essential oil for four days. both the study (peppermint
essential oil) and placebo
(sweet almond oil) groups.
Mint oil aromatherapy has

Inhalation 4 drops of mint
not been effective in
Pasha et al. [122] Iran Double-blind clinical trial. oil for four consecutive 60 Not mentioned.
reducing gestational nausea
nights before sleeping.
and vomiting.
It has been shown that that The severity of itching was

60 mL of peppermint oil
peppermint oil did not significantly reduced (p =
Akhavan et al. [123] Iran Triple-blind clinical trial. 0.5% in sesame oil/twice a 96
create any special side 0.001) in peppermint group
day for 2 weeks.
effects on subjects. vs. placebo group.
Studies in human
pregnancy have shown no
Asian countries: Iran,
Eight Various Not shown any harmful adverse effect of
Ahmed et al. [125] Malaysia, Palestine, Iraq, 2729
cross-sectional studies. pharmaceutical orms. effect to mother or fetus. peppermint. Excessive dose
Jordan, Oman, and Egypt
can induce menstruation
and cause miscarriage.
Table 7. Cont.
A total of 48.4% of women

Cross-sectional analytic Participants used of used herbal medicines
Abdollahi et al. [126] Iran 320 Not tested.
study 20 herbs during pregnancy, of which
19.81% used peppermint.
After 7 days of intervention,

the mean scores of Rhodes
index and severity of
Inhalation of four drops of
Quasi-experimental nausea and vomiting in the
Amzajerdi et al. [127] Iran pure mint oil twice a day for 66 Not tested.
interventional study. intervention group were
seven days of treatment.
significantly (p < 0.001)
lower than in the
control group.
On the third day of essential

oils inhalation, significantly
Inhalation of mixed two decreased (p < 0.0001)
perfumes of lavender and nausea and vomiting
Randomized controlled peppermint oils (2 drops of episodes in the study group
Ghani et al. [128] Saudi Arabia 101 Not mentioned.
trial. essential oil per 100 drops of compared with baseline.
carrier oil) twice a day, prior Significance increase in
napping or sleeping. energy level associated with
little decrease in
fatigue score.
5. Conclusions
Herbal medicines are used during pregnancy worldwide with a different prevalence
depending on traditions and geographical diversity of the region. In the Ethiopian popula-
tion, rural residency, illiteracy, and low average monthly income significantly predicted
the usage of herbs in pregnancy [6,78]. The nature of scientific approach to phytotherapy
has changed over the years. The “CAMbrella” project, funded by the European Union and
implemented between 2010 and 2012, was one of the first attempts of a comprehensive
approach to the problem of CAM, with phytotherapy included [129,130]. Previously, active
herbal compounds were tested mainly in vitro and in vivo, while currently, clinical settings
have started being more common. Nevertheless, there are still little clinical data analyzing
herbal products in pregnant women and when they do exist, they are carried out on a small
number of participants and therefore offer statistically weak results.
Our review of available data regarding the usage of herbal remedies to counteract the
ailments during pregnancy shows that ginger is one of the most extensively analyzed. In
pregnant women with hypereremesis gravidarum, taking 1 g of ginger per day resulted in
a significantly higher mean relief score compared to the placebo group [85]. In addition,
ginger was observed to have comparable effect to vitamin B6 [83]. Experimental data
on animal models showed that ginger in a dose below 1000 mg/kg did not cause any
toxicity but doses of 1000 mg/kg or 2000 mg/kg resulted in maternal toxicity [76]. Data
on pregnant women also did not report increased frequency of adverse effects from use of
ginger in a dose below 1000 mg. Therefore, its usage during pregnancy seems to be safe
both for future mother and for developing fetus.
Data regarding other herbs are most often heterogeneous and give conflicting results
with no clear conclusions. Of these, garlic intake during pregnancy may significantly
reduce the risk of both early and late spontaneous preterm delivery [50]. Several data
also reported the beneficial effects of inhalation with peppermint oil to relieve nausea and
vomiting [120,121,127]. However, there is still not enough evidence to prove the effec-
tiveness of cranberries, Echinacea, Ginkgo biloba, chamomile, or peppermint in pregnant
women. This uncertainty is also evident in the guidance of drug approval authorities, as
ginger is “generally regarded as safe” by the FDA, while the Finnish Food Safety Authority
does not recommend ginger products during pregnancy due to the lack of known safe
consumption limits.
The main limitations of the present review were the quantity and quality of the
available data, which creates difficulty in drawing obvious conclusions. Some symptoms
relief has been shown with the use of certain herbs, but these data may not be transferable to
different disease severities. Undoubtedly, all herbal products should be used with a special
caution in pregnancy, as safe consumption limits are lacking. Further methodologically
reliable studies on larger groups of pregnant women are needed to confirm the safe doses
of herbal products, which could be used by pregnant or breastfeeding women.
Author Contributions: Conceptualization, B.S.-H.; methodology, B.S.-M. and B.S.-H.; formal analysis,
B.S.-M. and B.S.-H.; investigation, B.S.-M. and B.S.-H.; resources, B.S.-M. and B.S.-H.; writing—
original draft preparation, B.S.-M. and B.S.-H.; writing—review and editing, B.S.-M. and B.S.-H.;
visualization, B.S.-M. and B.S.-H.; supervision, B.S.-M. and B.S.-H.; project administration, B.S.-M.
and B.S.-H. All authors have read and agreed to the published version of the manuscript.
Funding: The APC was funded by Medical University of Silesia in Katowice.
Institutional Review Board Statement: Not Applicable.
Informed Consent Statement: Not Applicable.
Data Availability Statement: Not Applicable.
Conflicts of Interest: The authors declare no conflict of interest.
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pharmaceutics

1 Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec,

Academic Editor: Cheong-Weon Cho

Pharmaceutics 2022, 14, 171. https://doi.org/10.3390/pharmaceutics14010171 https://www.mdpi.com/journal/pharmaceutics

3. Herbal Medicines Used to Counteract Infections during Pregnancy

3.2. Echinacea purpureae L. (Moench.)

Previously, the possible influence of Echinacea purpurea extracts on angiogenic activity

3.3. Garlic (Allium sativum)

Maternal garlic oil therapy:

Out of 18,888 deliveries, 950 (5.0%)

4. Herbal Medicines Used to Counteract Some Pregnancy-Related Symptoms (e.g.,

4.2. Ginger (Zingiber officinale Rosc.)

4.3. Gingko biloba L.

1st group: ginger capsules

4.4. Peppermint (Mentha piperita)

Peppermint is often used to relieve nausea and vomiting in pregnancy. Experimental

Two experimental groups receiving 600 mg/kg/day and 1200

Inhalation with three drops Nausea and vomiting

Before and during the

Mint oil aromatherapy has

It has been shown that that The severity of itching was

A total of 48.4% of women

After 7 days of intervention,

On the third day of essential

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