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REVIEW
Caraway as Important Medicinal Plants in Management of Diseases
Mohaddese Mahboubi
1
Received: 2 August 2018 / Accepted: 19 October 2018
ÓThe Author(s) 2018
Abstract
Carum carvi or caraway is traditionally used for treatment of indigestion, pneumonia, and as appetizer, galactagogue, and
carminative. Essential oil, fixed oil and many other valuable extractive compounds with industrial applications are prepared
from caraway. This review article has new deep research on caraway as medicinal plant. For preparing the manuscript, the
information was extracted from accessible international databases (Google scholar, PubMed, Science direct, Springer, and
Wiley), electronic resources and traditional books by key word of caraway or Carum carvi. The results of traditional
studies exhibited that the galactagogue and carminative effects of caraway fruits are superior to other effects. Although, the
traditional scholars used it as appetizer, while caraway was the main ingredient of anti-obesity drugs in traditional
medicine, which has been confirmed in two modern clinical trials of human studies. Caraway oil in combination with
peppermint oil or menthol is used for treatment of functional dyspepsia in clinical studies. Caraway oil topically on
abdomen relieves the IBS symptoms in patient. Although, the use of caraway oil is not recommended in adults under
18 years due to insufficient data, but it can topically use as anti-colic and carminative agent in children or infants. The anti-
aflatoxigenic, antioxidant and antimicrobial effects of caraway oil along with its reputation as spice help the industries to
use it as natural preservatives and antioxidant agents.
Keywords Caraway Carum carvi Obesity Functional dyspepsia Preservative Carvone Limonene
1 Introduction
Carum genus has 25 species, which Carum carvi or car-
away is the only annual and biennial economical one as
spice, aperitif, and carminative in food and pharmaceutical
industries. Caraway is widely used in food products due to
its pleasant flavor and preservative properties. Caraway
fruits are used as remedy to cure indigestion, pneumonia,
and as carminative, appetizer, and galactagogue in different
traditional systems [1,2]. According to European Union
herbal monograph, caraway is traditionally used for
symptomatic relief of digestive disorders (bloating and
flatulence). Caraway fruits are used as popular remedy to
mask alcoholic breath, anemia, and as antidote agent
against venomous beats. Caraway fruits are used for
flavoring of rye bread and its infusion is a remedy for colic
and digestive disorders, and to fight worms [3]. Caraway
fruits possess stimulant, expectorant and antispasmodic
effects and is used for stomach aches, constipation, and
nausea. It increases the secretion of gastric juice and pro-
motes the discharge of bile, which increases the appetite
and has digestive stimulatory effects [4]. Caraway is rec-
ommended by Persian traditional scholars to relieve the
flatulence. It acts by improvement of digestive systems and
deletion of accumulated gas from gastrointestinal tract,
humors from stomach, which also relives the abdominal
pain. For this purpose, the powder containing ajwain
(Trachyspermum ammi), anise (Pimpinella anisum), cumin
(Cuminum cyminum) and caraway with little rock candy is
used daily as three teaspoons [5]. Ibn Sina traditionally
used caraway for weight loss [6], stomach ache, burping,
flatulence and intestinal spasms [7]. Caraway fruits are the
main part of Safoof-e-Mohazzil, which is traditionally used
as weight loss compound [8]. In Iranian folk medicine,
caraway seeds are believed to possess the antiepileptic
effects [9]. Caraway leaves with garlic are used for treat-
ment of inflamed eczema by Indonesian people. Caraway
&Mohaddese Mahboubi
mahboubi1357@yahoo.com
1
Medicinal Plants Research Department, Research and
Development, TabibDaru Pharmaceutical Company, Kashan,
Iran
123
Natural Products and Bioprospecting
https://doi.org/10.1007/s13659-018-0190-x(0123456789().,-volV)(0123456789().,-volV)
tea is secreted in the milk with anti-griping effects on
digestive tracts of breast feeding babies [10]. An ointment
containing powdered fruits in Vaseline is used for animal’s
scabies. Caraway fruits contain valuable therapeutic
greenish-yellow essential oil (3–7%), which is used in
many therapeutic formulations from ancient times. Car-
away oil and thyme oil or caraway oil alone in ethanol
(15 mL) and castor oil (150 mL) are used for scabies and
mycosis [11,12]. For supporting the digestive function and
relief of colic and flatulence, a few drops of caraway oil are
added to olive oil and topically are rubbed over the pit of
stomach or abdomen [4,13]. Although, two review articles
have been published [7,8] on pharmacological activities of
caraway, but the difference of our review with others is the
deepness of our views on caraway. For preparing the
manuscript, the information was extracted from accessible
international databases, electronic resources (PubMed,
Science Direct, Springer, Wiley and Google), and tradi-
tional books (Persian or English modern traditional books),
by key word of caraway or Carum carvi.
2 Chemical Composition of Caraway
Caraway fruits contain essential oil (3–7%), fatty acids
(10–18%) (petroselinic, linoleic and oleic acids), protein
(20%), carbohydrate (15%) [14], phenolic acids (caffeic
acids), flavonoids (quercetin, kaempferol) [15,16]. Tan-
nins, alkaloids and terpenoids were present in caraway
aqueous extract [17]. Caraway oil is present in all parts of
plant, but its concentration is highest in its fruits and is
extracted by hydro-distillation method. Caraway chaff oil
is produced by hydro-distillation of husks and stalks and
contains less carvone and more terpenes. Caraway oleo-
resin is prepared from crushed dried caraway fruits by
solvents (hexane ethanol, ethyl acetate, ethylene dichlo-
ride), which has greenish shade of yellow color, normally
contain essential oil (20–25%), and fixed oil (60–75%).
Environmental conditions have essential effects on seed
quality, in other word, hot and dry weather is associated
with significant low quality fruits [18]. Changes in quality
of fruits mean the variation in main and major components
of plant.
Fatty acids such as petroselinic, linoleic and oleic acids
contain 10–18% of caraway fruits. A comparative study on
fatty acid contents of caraway fruits among Tunisian,
German and Egyptian ecotypes exhibited that the Tunisian
chemotype had the higher total fatty acid composition
(7.3%), followed by German (5.7%) and Egyptian (2.9%)
ecotypes. Petroselinic acid was the major fatty acid in three
ecotypes with percent of 31.1%, 30.9% and 29.5% in
Tunisian, German and Egyptian caraway fruits. The cor-
responding linoleic acid contents were 28.7%, 30.0% and
29.2% in these oils. Oleic acid was present about 27.5%,
21.6%, 21.2% in Tunisian, German and Egyptian caraway
fruit fixed oil. Myristic acid, palmitic, stearic and linoleic
acids were present at low levels in fatty oils. The unsatu-
rated fatty acids were higher in Tunisian ecotype (87.8%),
followed by German (82.9%) and Egyptian (80.8%) sam-
ples. Saturated fatty acids (12.1–19.2%), monounsaturated
(50.5–56.2%), polyunsaturated (30.2–31.6%) acids were
the chemical profile of fatty acids [19]. Total fatty acid
content of Tunisian annual caraway fruits from three eco-
types varied from 2.95 to 5.68% (w/w). Saturated (myristic,
palmitic and stearic acids), monounsaturated (petroselinic
acid), polyunsaturated (linoleic acid) fatty acids were pre-
sent in three ecotypes [20]. L-fenchone (55.0%), p-methoxy
benzaldehyde (19.2%) and p-methoxy allyl benzene (9.4%)
were identified in caraway fixed oil (yield 4.5%), which is
extracted by soxhlet apparatus with petroleum ether [21]. A
significant reduction in fatty acid content, seed yield and
growth parameters was observed under water deficient
[22].
Carvone and limonene are two major components of oil,
which account for 95% of essential oil compounds.
According to European Pharmacopeia, caraway fruit
should contain 3% essential oil with D-carvone (50–65%),
and (?)-limonene (up to 45%) as main components and it
contains less than 1.5% carveol and dihydrocarveol. D-
carvone as the main component of caraway [23]is
responsible for caraway odor reminiscent [24].
Many different factors have essential effects on yield
and chemical compositions of caraway essential oil. Harsh
conditions (heat and pH) have little effect on carvone and
limonene content of essential oil, while the changes in
minor components are very major [25]. Harvest time before
maturation lead to lower essential oil content than that of
full ripeness of caraway fruits. Also, the amount of carvone
enhances during and after maturation [26]. The higher
limonene to carvone ratio is proposed to be responsible for
better quality of caraway. Increasing the storage time
decreases the essential oil’s content and limonene to car-
vone ratio [27].
The limonene and carvone content increase under water
deficit. The yield of fruit essential oil increases under water
deficit [22]. Drying the seeds and reduction in fruit grinded
powder size increase the essential oil yield [3]. Method of
essential oil extraction, grinding methods, harvest time
change the essential oil yields and their chemical compo-
sition. Extraction of oil from whole seed results in high
content of carvone, while grinded fruits and their full
ripeness result in high essential oil yield [28]. The use of
ultrasound method for extraction of caraway oil results in
higher content of carvone than limonene. Carvone and
limonene yields were 1.3–2 times higher in ultrasound
assisted extraction method, depending on temperature, than
M. Mahboubi
123
hydro-distillation method [29]. The reason is destructive
mechanical effects of ultrasound method on fruits cell
walls, which increases the leakage of cell content, while in
hydro-distillation method, the plant extracts diffuses across
glandular walls and causes cell rupture over a long time.
Ultrasound treatment of caraway fruit result in release of
essential oil after 30 min of extraction with the same yield
for untreated fruit (1.72% vs. 1.68%) [30].
Limonene (48.1%), carvone (32.9%), and myrcene
(7.9%) were the main components of caraway fruit essen-
tial oil, extracted by hydro-distillation assisted by micro-
wave, while limonene (41.7%), carvone (55.8%), and
myrcene were present in accelerated steam distillation
assisted by microwave method [31]. Hydro-distillation by
direct induction heating assisted by magnetic field
(DIHMF) and by water and 6% food salt as electrolyte
solutions resulted in 2.11% (w/w) essential oil, where
limonene (7.4%) and carvone (85.2%) were its main
components. The essential oil yield for hydro-distillation in
presence of 6% food salt were 2.58%, with limonene
(18.7%), and carvone (74.9%) as the main components
[32]. Therefore, the isolation of essential oil by DIHMF is
as efficient as hydro-distillation method, because of shorter
time and higher quality of limonene and carvone. Carvone
(57.7%) and limonene (35.5%) were two major compo-
nents from ten identified compounds from Iranian caraway
essential oil by using ultrasonic assisted with headspace
solid phase micro-extraction (UA-HS-SPME) method [33].
The yields of essential oils obtained by hydro-distillation
and microwave-assisted hydro distillation methods from
Chinese caraway fruits were 4.7% and 4.2%, respectively.
Limonene (43.5%), carvone (32.6%), and apiole (15.1%)
were the main components of caraway fruits essential oil
extracted by hydro distillation method, while limonene
(48.4%), carvone (31.1%) and apiole (12.3%) were the
main components of oil extracted by microwave-assisted
hydro-distillation method [34].
The organ part of caraway causes changes in essential
oil yield and its chemical profile. Dried ripped fruit car-
away oil by hydro-distillation method consists of germa-
crene D (75%), caryophyllene, elemene, humulene,
germacrene A and B, and two cadinenes. Germacrene B
(51%) was the main component of seedlings root oil, which
decreases during development [35].
Geographical location (Table 1) of gathered caraway
fruits had greater effect than genotype on chemical com-
position of essential oil, while genotype had greater effects
than location on morphological traits of fruits [36].
A comparative study on essential oil yields and their
chemical compositions of different ecotypes exhibited that
the yields for essential oil extractions were 1.41%, 1.21%
and 0.48% for Tunisian and German and Egyptian eco-
types. Carvone (61.6–77.4%) and limonene (16.2–29.1%)
were the main components of caraway oils. Carvone
(77.3%), and limonene (16.2%) were the main components
of German caraway essential oil, while the corresponding
values were 76.3% and 19.5% for Tunisian chemotype.
Carvone (61.6%), limonene (29.1%), b-myrcene (3.9%)
and a-selinene (10.9%) were the main components of
Egyptian chemotype [19]. Limonene (43.5%), carvone
(32.6%), and apiole (15.1%) were the main components of
thirty-four components from Chinese caraway seeds
essential oil extracted by hydro-distillation method [34].
The essential oil yield from caraway cultivated in five
locality of Uttarakhand Himalaya, India were 3.3–4.8%.
Carvone (65.77–78.8%), and limonene (19.38–31.64%)
were the essential oil’s main components [37].
The essential oil yields varied from 0.6 to 5.4% for
twenty commercial caraway samples from different coun-
tries. Carvone (44.5–95.9%), limonene (1.5–51.3%), b-
myrcene (0–0.4%), trans-dihydrocarvone (0–0.5%), and
trans-carveole (0–0.2%) were present in these essential oils
[38].
Essential oil yields from three Tunisian ecotypes were in
the ranges of 0.86%–1.20% (w/w). Carvone (76.8–80.5%)
and limonene (13.1–20.3%) were the main components of
41 volatile compounds [20]. c-Terpinene (17.86%), cumi-
naldehyde (22.1%), c-Terpinene-7-al (15.41%), and
p-cymene (7.99%) were the main components of caraway
oil from Iran [39]. Therefore, due to the effects of many
factors on chemical composition of essential oil and the
amounts of each compounds, consideration to chemical
composition of caraway oil is inevitable (Fig. 1).
3 Biological Activities of Caraway Essential
Oil
3.1 Antimicrobial Effects of Caraway
The antimicrobial activity of caraway essential oil has been
the subject of some in vitro studies. Egyptian caraway
essential oil with limonene (53.4%), b-selinene (11.1%), b-
elemene (10.1%) and caryophyllene oxide (9.8%) as the
main components showed antibacterial activity against
Staphylococcus aureus,Salmonella typhi,Candida albi-
cans,Aspergillus niger and Listeria innocua with MIC
value lower than 1 lg/mL. Pseudomonas aeruginosa had
less sensitivity to Egyptian caraway essential oil (MIC [
16 lg/mL) [40]. Caraway oil with limonene (46.8%), and
carvone (52.3%) as main components showed the MIC
value of 18.8 ±10.3 lL/mL against clinical isolates of S.
aureus (n = 14) from skin lesions of patients. The MIC
value of caraway essential oil on S. aureus ATCC 29213
was 2.1 ±0.9 lL/mL [41]. Pullulan films (10%) contain-
ing caraway essential oil (0.12–10%) with carvone
Caraway as Important Medicinal Plants in Management of Diseases
123
(52.2%), limonene (43.5%) inhibited the growth of Sal-
monella enteritidis,S. aureus, Saccharomyces cerevisiae,
and Aspergillus niger on baby carrots samples. S. enteri-
tidis was the most resistant microorganism among the
others. Caraway essential oil inhibited S. cerevisiae,Can-
dida krusei (MIC = 0.06, MFC = 0.12%), S. aureus,B.
subtilis,Penicillium expansum (MIC = 0.12%, MLC =
0.12%), followed by S. enteritidis,Escherichia coli and A.
niger with MIC and MLC values of 0.12% and 0.25% [42].
Caraway essential oil showed anti-Candidal effects against
C. albicans isolates with MIC and MFC values of
0.03–0.11 and 0.06–0.11 mg/mL, respectively [43]. c-Ir-
radiation had no effect on major compounds of essential oil
and its antibacterial activities. Cumin aldehyde, c-ter-
pinene, c-terpinene-7-al and p-cymene had no change after
irradiation. The antibacterial effects of treated and
untreated caraway oil were the same against B. subtilis,S.
aureus,E. coli and P. aeruginosa [44]. Caraway oil showed
antibacterial activity against S. aureus (1 mg/g), and E. coli
(10 mg/g) [45].
Caraway essential oil with c-terpinene (17.9%), cumi-
naldehyde (22.1%), c-terpinene-7-al (15.4%), and p-cym-
ene (8.0%) significantly inhibited aflatoxin production
without any effects on Aspergillus parasiticus growth (IC
50
621.9 and 56 lg/mL for AFB1 and AFG1, respectively)
[39].
Topical caraway hydro-alcoholic extract with c-ter-
pinene (37.2%), cumin aldehyde (18.4%), p-cymene-7-ol
(13.6%) and p-cymene (10.9%) showed the high antibac-
terial activity against S. epidermidis (MIC = 0.39,
MBC = 1.56 mg/mL), S. intermedius (MIC = 0.76,
MBC = 1.56 mg/mL), followed by Streptococcus san-
guinis (MIC = 1.56, MBC = 3.125 mg/mL), S. mitis and
Campylobacter spp. (MIC = 1.56, MBC = 6.25 mg/mL),
respectively [46]. Phenolic compounds from defatted car-
away powder exhibited antibacterial effects against B.
cereus,S. aureus, followed by E. coli, and S. typhimurium
[47]. The results of above studies imply on the antibacte-
rial, antifungal and anti-candidal effects of caraway oil,
although its main components play an important role in its
antimicrobial effects. The antimicrobial effects of caraway
essential oil has a negative correlation with carvone con-
tent, while limonene content of essential oil has positive
correlation with antibacterial activities of essential oil [48].
Caraway is an inhibitor of P-gp efflux pumps [49]. It is
recommended to evaluate the antiviral and anti-dermato-
phyte effects of caraway oil.
3.2 Antioxidant Activity of Caraway
Free radicals are the reason of many ailment in the body or
deterioration of compounds in different industries, so the
antioxidant of compound is valuable [50].
C-irradiated caraway essential oil significantly reduced
DPPH radicals higher than trolox (20.7% vs. 12.6%). The
inhibitory effects of c-irradiated caraway essential oil on
peroxidation process of linoleic acid were not affected
from irradiation [44].
The protective effects of oral caraway oil (10 mg/kg) on
gentamicin induced nephrotoxicity has been confirmed in
rat animal model. Caraway essential oil reduced the
increased plasma malondialdehyde (MDA) in rats exposed
to gentamicin. It also increased superoxide dismutase
(SOD), catalase (CAT) and glutathione peroxidase (GSH-
Px) in rats [51]. The enhancing effects of oral caraway oil
(5, 10, 20 mg/kg) on serum level of GSH-Px, CAT and
Table 1 Chemical composition of Caraway oil from different geographical region
Country Yield (w/
w)
Main components References
German caraway
essential oil
1.21% Carvone (77.3%), and limonene (16.15%) [19]
Tunisian chemotype 1.41% Carvone (76.3%), and limonene (19.52%) [19]
Egyptian chemotype 0.48% Carvone (61.58%), limonene (29.11%), b-myrcene (3.97%) and a-selinene (10.9%) [19]
Egyptian chemotype – Limonene (53.4%), b-selinene (11.1%), b-elemene (10.1%) and caryophyllene oxide (9.8%) [40]
Chinese caraway 4.7% Limonene (43.5%), carvone (32.6%), and apiole (15.1%) [34]
Uttarakhand
Himalaya, India
3.3–4.8% Carvone (65.77–78.8%), and limonene (19.38–31.64%) [37]
Commercial
caraway
0.6–5.4% Carvone (44.5–95.9%), limonene (1.5–51.3%), b-myrcene (0–0.4%), trans-dihydrocarvone
(0–0.5%), and trans-carveole (0–0.2%)
[38]
Tunisian ecotype 0.86–1.20% Carvone (76.78–80.53%), and limonene (13.05–20.29%) [20]
Iran – c-Terpinene (17.86%), cuminaldehyde (22.1%), c-Terpinene-7-al (15.41%), p-cymene
(7.99%)
[39]
M. Mahboubi
123
SOD and the decreasing effects on serum level of MDA in
streptozotocin induced diabetic rats were confirmed. In
other word, caraway oil has reducing effect on the oxida-
tive stress in diabetes mellitus [52]. The preventive effects
of 100 mg/kg essential oil against cecal ligation and
puncture model, which induced septic related oxidative
liver injury in rats showed myeloperoxidase (MPO) activity
and TBARS were suppressed by essential oils in cecal
ligation and puncture model of rats. Caraway oils signifi-
cantly reverse the depleted hepatic cellular Glutathione
(GSH) comparable with 10 mg/kg indomethacin. Caraway
essential oils had significant suppressive effects on aspar-
tate transaminase (AST) and alanine transaminase (ALT).
Plasma alkaline phosphatase (ALP), total bilirubin, albu-
min and total protein were not affected from caraway
essential oil. Essential oils reduced infiltration and
sequestration of PMN, interstitial edema, congestion,
necrosis and the severity of liver injury index in sepsis
model of rats, comparable to indomethacin [53]. The reno-
protective effects of oral caraway essential oil (10 mg/kg)
in streptozotocin induced diabetic rats were shown by
increasing in GSH-Px to normal levels of control group and
significant improvement in pathology of diabetic
nephropathy with minor pathological changes in glomeru-
lar lobulation, mild cellular infiltration in interstitial tissue
[54]. Caraway (30, 60 and 90 mg/kg) for 30 weeks reduced
the levels of intestinal, colonic and caecal tissue lipid
peroxidation products (conjugated dienes, lipid hyperox-
ides, TBRAS) and increased the antioxidant enzymes such
as SOD, CAT, GSH, glutathione reductase of rats with
colon carcinogenesis. Caraway seed extract reduced the
activity of tissue GSH-Px, glutathione S transferase (GST),
ascorbic and a-tocopherol levels. Caraway fruits could
decrease the tumor size and tumor incidence. Caraway
make resistant the tumor cells to free radical attack, which
result in reduction of cell proliferation of cancerous cells.
The activation of antioxidant enzymes scavenge the free
radicals in colon cancer rats [55]. The protective effects of
150 mg/kg oral caraway seed aqueous extract on liver,
kidney and fertility exposed to cadmium toxicity in rat
animal model was confirmed. Caraway Seed extract
decreased the AST and ALT enzymes levels. The serum
level of creatinine had the same value with control group.
A significant increase in total antioxidant capacity and a
significant reduction in serum levels of MDA was observed
in caraway female rats. The histopathological samples of
liver from caraway treated rats showed normal structures
with strong fuchsinophilic reaction in hepatocytes. Pre-
treatment of cadmium treated rats with caraway seed
extract improved the histopathological structure of kidney
tubules. An improvement in liver functions was observed
after treatment of cadmium exposed albino rats with car-
away seed extract, which maintain the liver enzymes in
normal level. Caraway seed extract had ameliorative
effects against hepatic histological changes induced by
cadmium [56].
Topical application of caraway hydro-alcoholic extract
on oral mucositis induced by 5-fluorouracil in golden
hamsters improved histological parameters in 5-fluo-
rouracil induced mucositis, which is associated with
reduction in oxidative stress of oral mucosa [46]. Cold-
pressed caraway fixed oil with high total phenolic content
showed high radical scavenging activities in different
antioxidant system with inhibitory effects on human LDL
oxidation [57]. Caraway with high total phenolic content
had been good reducing power in different in vitro
Fig. 1 The chemical structure of main components of caraway fruits
Caraway as Important Medicinal Plants in Management of Diseases
123
antioxidant system [58]. It has been confirmed high level of
flavonoids [59] and steroid like substances of caraway
inhibited CYP1A1 at mRNA level, which generates reac-
tive metabolites that are toxic or carcinogenic metabolites
with binding property of attachment to DNA [60].
3.3 Anti-diabetic Effects of Caraway
Oral caraway essential oil (10 mg/kg) decreased the fasting
blood sugar in streptozotocin induced diabetic rats [54].
Streptozotocin induced diabetic rats treated with oral doses
of caraway oil (5, 10, 20 mg/kg) had higher weight and
lower level of blood glucose in comparison with control
group [52]. The effects of caraway oil on serum blood
glucose [52] and no effectiveness of plasma level of insulin
from caraway oil imply that reduction in serum level of
glucose is regulated by a mechanism independent of insulin
secretion [61]. The antioxidant effects of caraway oil may
involve in anti-diabetic effects of caraway oil.
3.4 Anti-inflammatory Effect of Caraway
Oral caraway essential oil (10 mg/kg) reduced the pro-in-
flammatory cytokines (IFN-c, IL-6 and TNF-a) in rats
exposed to gentamicin [51]. Oral and intra-peritoneal
administrations of caraway hydro-alcoholic extract (100,
200, 400 mg/kg) and its essential oil (100, 200, 400 lL/kg)
in an immunological model of colitis of rats induced by
trinitrobenzene sulfonic acid (TNBS) reduced colon tissue
lesions and colitis index, comparable to prednisolone and
Asacol
Ò
. Caraway extracts and its essential oil reduced the
inflammation and infiltration of white blood cells in mucus
and sub-mucosal layers [62]. The immunological effects of
caraway has been confirmed [63].
Therefore, caraway can be a good candidate for man-
agement of inflammatory diseases such as Irritable Bowel
Syndrome (IBS), and Inflammatory bowel disease (IBD).
3.5 Anticonvulsant Effects of Caraway
The antiepileptic effects of caraway [9] have been the
subject of study according to folk believes. Caraway
aqueous extract (200, 400, 800, 1600 and 3200 mg/kg i.p)
and essential oil (25, 50, 100, 200 and 400 mg/kg, i.p) in
comparison with diazepam (3 mg/kg) in pentylenetetrazole
(PTZ) induced convulsion of mice animal model dose
dependently increased the latency time the onset of myo-
clonic and clonic seizures. Caraway oil or its extract had
preventive effect against tonic seizure and PTZ induced
death. The anticonvulsant effects of essential oil was higher
than its aqueous extract. Essential oil or extract had no
effect on neuromuscular coordination. Therefore,
relaxation of muscle was not involved in its anticonvulsant
effects [17].
3.6 Diuretic Effects of Caraway
The ripe fruits of caraway is used as diuretic in Moroccan
Traditional Medicine. The diuretic effects of acute and sub-
chronic oral dose of 100 mg/kg caraway seed aqueous
extract was compared with 10 mg/g furosemide in normal
male Wistar rats. Caraway seed extract increased the urine
output, total volume of excreted urine, urinary level of K
?
and Na
?
comparable with furosemide in except of urinary
K
?
level. The plasma K
?
and Na
?
was not affected from
caraway seed extract. The administration of caraway seed
aqueous extract for 8 days showed strong diuretic effects
and virtually had no effect on urinary K
?
excretion for the
entire 8 days. Caraway seed extract had no renal toxicity
during 8 days of treatment [64].
3.7 Anti-glycemic Effects of Caraway
Caraway seed aqueous extract decreased the cholesterol
and triglycerides in normal and streptozotocin diabetic rats.
Six hours after oral administration of 20 mg/kg caraway
seed aqueous extract, the plasma level of triglycerides and
cholesterols of normal rats decreased. Oral single dose of
caraway seed extract decreased the plasma cholesterol
levels only in streptozotocin induced rats. No change was
observed in plasma triglycerides concentration in caraway
treated streptozotocin induced rats. Repeated oral admin-
istration of caraway extract for 15 days significantly
reduced the plasma triglycerides in normal and streptozo-
tocin rats [65].
3.8 The Effects of Caraway on Reproductive
Organs
The modulation effects of caraway on sexual function and
fertility in females have been claimed in Egyptian folk
medicine. 150 mg/kg oral caraway seed aqueous extract on
fertility organ exposed to cadmium toxicity in rat animal
model increased the serum estrogen in proestrus phase of
cadmium treated rats. Atretic follicles and minor degen-
erative changes, stratified uterine epithelium and cystic
endometrial gland with weakly reacted glands was
observed in caraway treated rats, which exposed to cad-
mium. Caraway fruit aqueous extract showed antifertility
effects, it significantly increased the estrogen level and
reduced the progestrone and FSH levels at proestrus phase
[56]. Caraway aqueous or ethanol extracts from doses
higher than 200 mg/kg showed estrogenic effects. After
30 days administration of caraway extracts, changes in
vaginal smear, was observed. The ovary weight, uterus
M. Mahboubi
123
weight and estrogen levels increased, while gonadotropins
levels decreased [66].
3.9 Other Biological Activities of Caraway
The pharmacokinetic properties of paracetamol (oral,
intraperitoneal) are affected from chronic intake of car-
away oil [67]. Administration of 100 mg caraway with
rifampin, isoniazid and pyrazinamide in 20 healthy vol-
unteers increased the plasma levels of antibiotics. Caraway
increased the bioavailability indices C
max
of antibiotics and
area under curve (AUC) [68]. Caraway enhanced the action
of rifampicin [69], isoniazid and pyrazinamide in rats
[69,70]. KCl (80 mM) related tonic contraction and the
phasic contraction to acetylcholine (320 nM) of rat isolated
uterus dose dependently was inhibited by caraway essential
oil, which implicates to its usefulness for control of uterus
spasm [71]. Feeding the lactating cow with 0.2 and 1 g
caraway oil/kg dry matter for 24 days had no effect on food
consumption, methane emission and milk production. The
milk had higher fresher aroma and lower stored aroma [72].
Caraway oil had no effect on growth promotion and feed
intake in weaning piglet [73]. Caraway oil especially car-
vone is a good potato sprouting inhibitor [74]. The mol-
luscicidal activity of caraway seed powder, ethanol extract
with LC
50
140.58 mg/L after 96 h and 130.61 mg/L after
24 h was confirmed against snail Lymnaea acuminate and
may be due to limonene content [75].
4 The Efficacy of Caraway in Clinical Trials
of Human Diseases
4.1 Caraway in Management of Thyroid
Hormones
Caraway increased the TSH level in patients with papillary
thyroid carcinoma under treatment with fixed dose of
levothyroxine. 40 mg/kg/day caraway capsule and
100 lg/day levothyroxine in a hypothyroidism patients
increased TSH level, 2 weeks after ingestion of caraway.
Five months after discontinuation of caraway, the TSH
level returns to normal level. T
4
and T
3
levels decreased by
consumption of caraway [76]. The enhancing effects of
caraway on T
3
and T
4
, and decreasing effect on TSH [77]
and its anti-hypothyroidism effects stimulate metabolic
rate, which reduces body fat and body weight [78].
4.2 Caraway in Management of Obesity
According to ancient Unani medicine texts, obesity (Sa-
man-e-Mufrat) means excessive fat, which accumulates in
the body. It is a phlegmatic disease, which balgham
predominates in the body. Phlegm with blood produces
viscosity of the blood and constrict blood vessels. Depo-
sition of fat (Atherosclerosis) obstructs passage of oxygen
in the organs, which can cause death. It is recommended to
obese patients to eat 5 g Safoof-e-Muhazzil with 20 mL
Arq-e-Zeera (caraway water or distillate of caraway in
order to gathering the water containing soluble essential
oil), twice a day. There are some clinical studies, which
evaluates its efficacy.
In randomized, triple blind, placebo-controlled clinical
trial, the efficacy of caraway water on weigh loss of women
with BMI 25–39.9 kg/m
2
was evaluated in comparison
with placebo. Caraway water was prepared by hydro-dis-
tillation of 1 kg caraway fruits and producing 10 L car-
away water. Placebo was containing 1% g/L caraway
essential oil. The patients in each group are recommended
to use 30 mL intervention or placebo, 20 min before lunch
for 3 months. The patients were visited every week from
the beginning until the end of treatment. The regimen
program and any probable side effects were recorded
during the study. Clinical assessments on vital parameters
along with blood and urine tests and biochemical param-
eters were evaluated. The mean weight, BMI, waist cir-
cumference, waist-to-hip ratio and body fat percent
significantly reduced in caraway water compared to pla-
cebo group. The body muscle percent increased in caraway
water group. Vital clinical symptoms including heart rate,
systolic and diastolic blood pressure, urine specific gravity
and lipid profile had no significant difference with placebo
group [79]. A significant reduction in appetite level and
carbohydrate intake was observed after 90 days treatment
with caraway extract. Caraway extract had no significant
effect on fat and protein intake of the overweight subject,
compared to control group. All of the anthropometric
indices (waist circumference, waist to hip ratio, thigh cir-
cumference, and mid-upper arm circumference) exhibited a
significant reduction in caraway oil, compared with pla-
cebo group. The average appetite level significantly
reduced in caraway extract group [80]. The limitation of
two studies are placebo group. Indeed caraway water is a
kind of diluted caraway oil, which is used as placebo in this
study.
4.3 Caraway in Management of Functional
Dyspepsia
The most important application of caraway is its use as
remedy for digestive problems. In one clinical trial, the
efficacy and tolerability of enteric-coated capsule con-
taining caraway oil and menthol was compared to placebo
in Functional Dyspepsia patients (Rome III criteria) taking
their usual medications (PPIs, H2RAs, anticonvulsants,
beta blockers, antihistamines, antidepressants/TCAs, pain
Caraway as Important Medicinal Plants in Management of Diseases
123
modulators, and antiacids). Each capsule was containing
25 mg of caraway oil and 20.75 mg L-menthol. The
patients took two capsules of intervention or placebo, twice
daily, 30–60 min before a meal in the morning and at
dinner time for 28 days. Changes in Global Overall
Symptom and Clinical Global Impressions, safety and
tolerability were examined. The results of study showed
that the reduction of symptoms was numerically superior in
intervention group than that of placebo. 61% and 49% of
patients found intervention and placebo treatments ‘‘good’’
or ‘‘very good’’ in improvement of Clinical Global
Impressions (p = 0.23). No serious adverse events were
reported in intervention group [81].
In a prospective, double-blind, multicenter trial, 114
outpatients with chronic or recurrent functional dyspepsia,
the efficacy of peppermint-caraway-oil preparation
(n = 58) or placebo (n = 56) was evaluated on improve-
ment of abdominal pain and discomfort. The patients took
capsules, twice daily, in the morning and dinner. 8.6% and
5.4% in intervention and placebo groups left the study,
before the end of treatments. A significant improvement in
symptoms was observed in intervention group compared to
placebo group (p = 0.0004). The average symptom scores
reductions were 7.6 ±4.8 (62.3%) and 3.4 ±4.3 (26%) in
intervention and placebo groups (p \0.0001). The corre-
sponding at least 10% improvements were 86.2 and 57.1%,
respectively. Disease-specific symptoms, quality of life
(QoL) in patients with functional dyspepsia symptoms
improved consistent with epigastric pain syndrome and
postprandial distress syndrome [82].
The efficacy of caraway oil (50 mg) and peppermint oil
(41.5 mg) versus placebo over a treatment period of
28 days in reduction of Global Overall Symptoms (GOS)
and Clinical Global Impressions (CGI) of patients suffering
from functional dyspepsia were evaluated. At the end of
treatment, PDS (78%) and EPS (72%) patients in inter-
vention group reported the treatment ‘‘good’’ or ‘‘very
good’’ in CGI assessment, while the corresponding values
in placebo group were 50% (PDS) (p = 0.09) and 40%
(EPS) (p = 0.046), respectively. The sensations of pressure,
heaviness, fullness, reduction in epigastric pain or dis-
comfort symptoms improved no significantly compared to
placebo group [83].
The effect of capsule containing 25 mg of caraway oil
and 20.75 mg of L-menthol versus placebo for functional
dyspepsia symptoms was evaluated after 24 h. In this
study, 100 subjects suffering from functional dyspepsia
(Rome III criteria) took two capsules of intervention or
placebo in the morning and at dinner time. The patients
were categorized into PDS or EPS predominant based on
their symptoms and took their routine treatments. The self-
reported Global Overall Symptoms (GOS) were used in
patients at 24 h. At 24 h, a significant (p= 0.04) reduction
in PDS symptoms and significant improvement in EPS
symptoms (p = 0.076) in the overall population were
observed [83].
Enteric-coated and non-enteric-coated capsules, which
contain 90 mg peppermint and 50 mg caraway oil had
effects on the migrating motor complex of healthy volun-
teers and decreased the number of contractions and con-
traction amplitudes during the various phases of the
migrating motor complex. The effects of non-enteric-
coated capsule was mainly during the first migrating motor
complex after administration, while the effects of enteric-
coated capsule temporally had delayed during the second
migrating motor complex. Both capsules were safe and had
local smooth muscle relaxing effect [84].
Evaluating the efficacy of enteric-coated capsule con-
taining 90 mg peppermint and 50 mg caraway oil (twice
daily) on 118 patients suffering from functional dyspepsia
in comparison 30 mg cisapride daily on the base of pain
score (VAS), frequency of pain and dyspeptic symptom
score (DSS) showed that intensity of pain decreased from
6.6 ±1.3 to 2.0 ±2.2 in enteric-coated capsule group.
The corresponding values were 6.5 ±1.3 and 1.9 ±2.3 at
baseline and after twenty-ninth day in cisapride group. The
mean reduction in frequency of pain and DDS was com-
parable in two groups after 29 day (1.9 ±2.2 vs. 2.0 ±2.5
and 12.7 ±14.0 vs. 13.2 ±14.3, respectively). Twelve
and 14 patients in enteric-coated capsule and cisapride
experienced non-serious adverse effects, which diarrhea
was reported as the most frequent symptoms [85].
In a prospective, randomized, placebo controlled mul-
ticenter trial, the effect of enteric-coated capsule on dys-
peptic symptoms and life quality of male with functional
dyspepsia after 2 and 4 weeks of evaluation on the base of
pain score, discomfort score, Nepean Dyspepsia index
symptom score, and Nepean Dyspepsia index total scores
showed that enteric-coated capsule was superior to placebo
in reducing all variables. Pain score, the discomfort score
and Nepean Dyspepsia index symptom score (p \0.000l)
and Nepean Dyspepsia index total score (p = 0.0037)
improved significantly compared to placebo. The treatment
was well tolerated and improved the quality of life in
patients [86]. For management of functional dyspepsia,
caraway oil is used in combination with menthol or pep-
permint oil.
4.4 Caraway in Management of Irritable Bowel
Syndrome (IBS)
In randomized controlled cross-over trial, the efficacy of
hot poultice made with caraway poultice in treatment of
IBS for 3 weeks, followed by 2 week ‘wash-out’ phases,
was compared with hot or cold poultices of olive oil. Forty-
eight patients with diarrhea dominant IBS were in this
M. Mahboubi
123
study. Two-third of patients applying caraway oil poultice
found the treatment good or very good. A significant dif-
ference in symptom severity were found among caraway
oil poultice and cold poultice. The response rate was
43.9%, 20% and 18.9% for caraway oil, hot or cold olive
oils, respectively. The IBS-QOL total score, subscales
health worry and dysphoria, Bristol stool scale had sig-
nificant difference in caraway oil with the others. The
treatment with caraway oil was without any adverse
effects. The adequate relief was reported 51.8%, 23.5% and
25.8% for caraway oil, hot or cold olive poultices [87].
Caraway is the active components of Iberogast as remedy
for treatment of gastro-intestinal motility, and as anti-in-
flammatory, anti-oxidant agents, which inhibit the gastric
acid production [88].
5 Daily Dose of Caraway
0.15–0.3 mL of essential oil in three divided daily dose is
recommended for adults and elders. The oral administra-
tion of caraway essential oil is not recommended for
children and adolescents under 18 years old, during lacta-
tion and pregnancy. Semisolid preparations of caraway oil
in concentration of 2% can be applied daily as a thin layer
on the abdominal area of infants, children, adolescents,
adults and elders [89]. Caraway fruits (1.5–6 g) or its
essential oil (0.15–0.3 mL) are described as carminative,
spasmodic gastro-intestinal complaints, bloating, flatulence
and sensation of fullness. 0.3 mL of caraway oil is corre-
sponded to 273 mg of caraway oil (density 0.91 g/mL).
Caraway aqueous or ethanol extracts from doses higher
than 200 mg/kg showed estrogenic effects [66].
6 Contraindication and Precaution
The use of preparation containing caraway oil on broken
skin, around the eyes or mucous membranes and in the
patients with liver disease, achlorhydria, cholangitis, gall-
stones or other biliary disorders is not recommended [89].
Caraway fruit or caraway oil is not recommended to use
during pregnancy and lactation due to insufficient data. A
warning of use in patients with obstruction of bile ducts,
liver diseases, cholangitis, gallstones or other biliary dis-
eases is present due to complete inhibitory effects of car-
away on gallbladder emptying in healthy humans [90]. The
contraindication with inflammation of kidneys was repor-
ted and overdoses of caraway oil for long time causes
kidney and liver damage [4].
7 Toxicity of Caraway
The acute oral and dermal LD
50
of caraway oil in rats and
rabbits were 3.5 and 1.78 mL/kg, respectively. Pure car-
away oil had no irritating effects on the backs of hairless
mice. Applying 4% caraway oil in petrolatum on 25 human
subjects had been no irritating and sensitization reactions
effects in a 48 h closed patch test [91].
In the ESCOP monograph, the acute oral LD
50
of car-
away oil in rats was reported from two different studies as
3.5 and 7.4 mL/kg, respectively. The acute dermal LD
50
of
caraway oil in rabbits was reported as 1.8 mL/kg. Intra-
peritoneal, intravenous LD
50
of D-carvone in mice were
482.2 and 1500 mg/kg, the oral LD
50
of D-carvone in rats
and guinea pigs were 1640 and 766 mg/kg. ADI (Accept-
able Daily Intake) for D-carvone was 0–1 mg/kg/day [90].
In a randomized, triple-blind, placebo-controlled study,
the safety of caraway aqueous extract was evaluated on 35
overweight and obese healthy women compared with pla-
cebo. The patients received 30 mL of caraway water or
placebo (diluted caraway essential oil) for 12 weeks, and
the general health status, urine test, blood pressure, heart
rate and blood chemistry were evaluated. No adverse
events were reported after 12 weeks of treatment. Heart
rate, liver, kidney functions were not affected from inter-
ventions. A significant difference in red blood cell and
platelet distribution width levels were observed among two
groups. A significant increase in red blood cell and sig-
nificant reduction in platelet distribution width were
observed in caraway water, which imply that the possible
beneficial effect of caraway seed aqueous extract for the
treatment of anemia. Hyperthyroidism is associated with an
reduction of platelet distribution width [78]. Caraway is
well tolerated in therapeutic doses and showed no toxic
effects toward human [10]. Acute toxicity of caraway
exhibited the maximum nonlethal dose of caraway essen-
tial oil and aqueous extract were 400 and 3200 mg/kg,
respectively [17]. The established ADI for D-carvone is
0.6 mg/kg bw/day [92].
8 Concluding Remarks and Future
Directions of Research
The review article has a deep view on caraway fruits as
famous medicinal plants in different pharmaceutical, food
and cosmetic industries. Caraway fruits are used in dif-
ferent traditional systems as curative plants for manage-
ment of different ailments, especially for management of
digestive disorders. In traditional medicine, the galacta-
gogue and carminative effects of caraway fruits are supe-
rior to other biological effects. Although, traditional
Caraway as Important Medicinal Plants in Management of Diseases
123
scholars use caraway fruits as appetizer in foods, but car-
away fruits or its water are one important ingredient of
anti-obesity drugs in Unani traditional medicine [93].
There are two parallel clinical trials, which confirmed the
anti-obesity effects [78,80] of caraway water (Zeereh-
Aragh) in comparison with placebo. Caraway reduces the
plasma triglycerides and cholesterol levels in normal and
streptozotocin rats [65] and also it enhances T
3
and T
4
levels. All above mechanisms along with its decreasing
effect on TSH [77], are proposed the activation of meta-
bolism in the body. The important role of caraway oil in
management of functional dyspepsia has been confirmed in
many clinical studies, but caraway oil always is used in
combination with peppermint oil or menthol in enteric
coated pills [85,86]. The topical use of caraway oil around
the abdomen has relieved the IBS symptoms in patient
[87]. Although, the use of caraway oil is not recommended
for adults under 18 days due to insufficient data, but it can
be topically used as anti-colic and carminative agent for
children or infantile. Although, caraway fruits are used for
treatment of many human disorders according to traditional
believes, the antiepileptic, anti-inflammatory, galactagogue
effects of caraway oil have been confirmed in pre-clinical
studies. Due to the high yield of essential oil, the use of
caraway oil as antioxidant [50,59] and preservatives [94]
in food industries are recommended. Caraway could act as
bioenhancers [49,95]. Evaluating the safety of topical
creams as abdominal pain reliever in children should be
considered. The anti-aflatoxigenic, antioxidant and
antimicrobial effects of caraway oil along with its reputa-
tion as spice help the industries to use it as natural
preservatives and antioxidant agents instead of synthetic
ones.
Compliance with Ethical Standards
Conflict of interest The authors declare no conflict of interest.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://creative
commons.org/licenses/by/4.0/), which permits unrestricted use, dis-
tribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
made.
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