Food Quality and Safety, 2018, 2, 1–16

doi:10.1093/fqsafe/fyx031
Review
Advance Access publication 24 January 2018

Review

Cumin (Cuminum cyminum) and black cumin

(Nigella sativa) seeds: traditional uses, chemical
constituents, and nutraceutical effects

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Krishnapura Srinivasan
Department of Biochemistry, CSIR – Central Food Technological Research Institute, Mysore, India

Correspondence to: Krishnapura Srinivasan, Department of Biochemistry, CSIR – Central Food Technological Research
Institute, Mysore 570 020, India. E-mail: ksri.cftri@gmail.com
Received 6 July 2017; Revised 26 July 2017; Editorial decision 15 August 2017.

Abstract
Although the seeds of cumin (Cuminum cyminum L.) are widely used as a spice for their distinctive
aroma, they are also commonly used in traditional medicine to treat a variety of diseases. The
literature presents ample evidence for the biomedical activities of cumin, which have generally
been ascribed to its bioactive constituents such as terpenes, phenols, and flavonoids. Those health
effects of cumin seeds that are experimentally validated are discussed in this review. Black seeds
(Nigella sativa), which are totally unrelated to C.  cyminum, have nevertheless taken the name
‘Black cumin’ and used in traditional systems of medicine for many disorders. Numerous pre-
clinical and clinical trials have investigated its efficacy using the seed oil, essential oil, and its
main constituent thymoquinone (TQ). These investigations support its use either independently or
as an adjunct along with conventional drugs in respiratory problems, allergic rhinitis, dyspepsia,
metabolic syndrome, diabetes mellitus, inflammatory diseases, and different types of human
cancer. Multiple studies made in the last decades validate its health beneficial effects particularly
in diabetes, dyslipidemia, hypertension, respiratory disorders, inflammatory diseases, and cancer.
Nigella sativa seeds also possess immune stimulatory, gastroprotective, hepatoprotective,
nephroprotective, and neuroprotective activities. TQ is the most abundant constituent of volatile
oil of N. sativa seeds, and most of the medicinal properties of N. sativa are attributed mainly to TQ.
All the available evidence suggests that TQ should be developed as a novel drug in clinical trials.

Key words: Cuminum cyminum; Nigella sativa; digestive stimulant; antidiabetic; anti-inflammatory; cancer preventive;
immune stimulatory; gastroprotective.

Introduction traditional medicine. In the Ayurvedic system of medicine in India,

cumin seeds have immense medicinal value, particularly for digestive
Cumin seeds (Figure 1) are obtained from the herb Cuminum
disorders. They are used in chronic diarrhoea and dyspepsia (Table 1).
cyminum, native from East Mediterranean to South Asia belonging
Black seed (also known as black cumin; Nigella sativa) (Figure 1)
to the family Apiaceae—a member of the parsley family. Cumin seeds
is an annual flowering plant belonging to the family Ranunculaceae
are oblong and yellow–grey. Cumin seeds are liberally used in several
and is a native of Southern Europe, North Africa, and Southwest Asia.
cuisines of many different food cultures since ancient times, in both
Black cumin is cultivated in the Middle Eastern Mediterranean region,
whole and ground forms. In India, cumin seeds have been used for
Southern Europe, Northern India, Pakistan, Syria, Turkey, Iran, and
thousands of years as a traditional ingredient of innumerable dishes
Saudi Arabia. Nigella sativa seeds and their oil have a long history of
including kormas and soups and also form an ingredient of several
folklore usage in Indian and Arabian civilization as food and medicine
other spice blends. Besides food use, it has also many applications in

© The Author(s) 2018. Published by Oxford University Press on behalf of Zhejiang University Press.
1
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2
Figure 1  Different varieties of cumin.
Figure 2.  Major bioactive compounds of cumin and black seeds.
Figure 3.  Multiple medicinal properties of Cuminum cyminum (cumin seeds).
(Yarnell and Abascal, 2011). The seeds of N. sativa have a pungent bit-
ter taste and aroma and are used as a spice in Indian and extensively in
Middle Eastern cuisines. The dry-roasted nigella seeds flavour curries,
vegetables, and pulses. Black seeds are used in food as a flavouring
additive in breads and pickles. It is also used as an ingredient of the
spice mixture (panch phoron) and also independently of many recipes
in Bengali cuisine. Cumin was traditionally used as a preservative in
mummification in the ancient Egyptian civilization. Black cumin has a
long history of use as medicine in the Indian traditional system of medi-
cine like Unani and Ayurveda (Sharma et al., 2005). The black cumin
seeds have traditionally been used in the Southeast Asian and Middle
East countries for the treatment of diseases such as asthma, bron-
chitis, rheumatism, and other inflammatory diseases. Nigella sativa
has extensively been used because of its therapeutic potential and pos-
sesses a wide spectrum of activities, namely, diuretic, antihypertensive,
antidiabetic, anticancer, immune-modulatory, antimicrobial, anthel-
mintic, analgesic and anti-inflammatory, spasmolytic, bronchodilator,
gastroprotective, hepatoprotective, and renal protective properties.
Traditionally, seeds of N. sativa are widely used for asthma, diabetes,
hypertension, fever, inflammation, bronchitis, dizziness, rheumatism,
skin disorders, and gastrointestinal disturbances (Table 1). It is also
used as a liver tonic, digestive, antidiarrhoeal, emmenagogue, and to
control parasitic infections and boost immune system (Goreja, 2003).
K. Srinivasan, 2018, Vol. 2, No. 1
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Bunium persicum (occasionally referred to as Cuminum nigrum;
also known as Shahi jeera), belonging to Apiaceae (parsley family),
is a smaller variety of cumin with a different flavour, popularly used
in North Indian, Pakistani, and Iranian foods (Figure 1). Until now,
there is only very little scientific information on this spice.
Chemical constituents
Cumin seeds are nutritionally rich; they provide high amounts of fat
(especially monounsaturated fat), protein, and dietary fibre. Vitamins
B and E and several dietary minerals, especially iron, are also con-
siderable in cumin seeds. Cuminaldehyde (Figure 2), cymene, and
terpenoids are the major volatile components of cumin (Bettaieb
et al., 2011). Cumin has a distinctive strong flavour. Its warm aroma
is due to its essential oil content. Its main constituent of aroma com-
pounds are cuminaldehyde and cuminic alcohol. Other important
aroma compounds of roasted cumin are the substituted pyrazines,
2-ethoxy-3-isopropylpyrazine, 2-methoxy-3-sec-butylpyrazine, and
2-methoxy-3-methylpyrazine. Other components include γ-terpinene,
safranal, p-cymene, and β-pinene (Li and Jiang, 2004).
Nigella sativa seeds contain protein (26.7%), fat (28.5%), carbohy-
drates (24.9%), crude fibre (8.4%), and total ash (4.8%). Nigella sativa
seeds also contain a good amount of various vitamins and minerals
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1 
Figure 4.  Multiple medicinal properties of Nigella sativa (black cumin seeds).
like Cu, P, Zn, and Fe. Many active compounds have been identified in
N. sativa. The most important active compounds of N. sativa are thy-
moquinone (TQ) (30%–48%) (Figure 2), thymohydroquinone, dithy-
moquinone (nigellone), p-cymene (7%–15%), carvacrol (6%–12%),
4-terpineol (2%–7%), t-anethole (1%–4%), sesquiterpene longifolene
(1%–8%), α-pinene, and thymol. (Boskabady and Shirmohammadi,
2002; Ali and Blunden, 2003). Nigella sativa also contains other com-
pounds such as carvone, limonene, citronellol in trace amounts, and
two varieties of alkaloids, i.e. isoquinoline alkaloids (e.g. nigellicimine
and nigellicimine-N-oxide) and pyrazole alkaloids (e.g. nigellidine
and nigellicine). Nigella sativa seeds also contain α-hederin, a water
soluble pentacyclic triterpene (Al-Jassir, 1992; Nickavar et al., 2003).
The pharmacological properties of N. sativa are mainly attributable
to its quinine constituents, TQ being the most abundant. The N. sativa
seeds contain fatty oil rich in unsaturated fatty acids, constituting lino-
leic acid (50%–60%), oleic acid (20%), eicosadienoic acid (3%), and
dihomolinoleic acid (10%), and saturated fatty acids (palmitic and
stearic acids) constitute up to 30 per cent. α-Sitosterol is the major
sterol, accounting for 44%–54% of the total sterols in N. sativa oils,
followed by stigmasterol (6.57%–20.9% of total sterols) (Cheikh-
Rouhou et al., 2008; Mehta et al., 2008).
Bitter cumin (Shahi jeera) seeds contain calcium, vitamin A, po-
tassium, sodium, iron, magnesium, and phosphorus. Bitter cumin
(B.  persicum) has 0.5 to 1.6 per cent essential oil, mainly carvone
(45%–60%), limonene, and p-cymene. Oleoresin of bitter cumin is
brownish to yellowish green. As there is not enough scientific infor-
mation on the health effects of bitter cumin, this review is limited
to C.  cyminum (cumin seeds) and N.  sativa (black seeds or black
cumin)
Health effects of C. cyminum
Although the seeds of cumin (C. cyminum L.) are widely used as the
spice for their distinctive aroma, they are also commonly used in
traditional medicine to treat a variety of diseases, including chronic
diarrhoea and dyspepsia, acute gastritis, diabetes, and cancer. The
literature presents ample evidence for the biological and biomedical
activities of cumin, which have generally been ascribed to its bio-
active constituents such as terpenes, phenols, and flavonoids (Mnif
and Aifa, 2015). Those health effects of cumin seeds that are experi-
mentally validated (Figure 3) are discussed below.
Digestive stimulant action
In the context of cumin seeds being claimed in home remedies and
traditional medicine, to aid digestion, an animal study has examined
3
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whether they have any stimulatory effect on the digestive enzymes.
The influence of cumin seeds on the digestive enzymes of the rat pan-
creas and intestinal mucosa has particularly been investigated as a
result of both continuous dietary intake and single oral administra-
tion (Platel and Srinivasan, 1996; 2000a) (Table 2). Dietary (1.25%)
cumin lowered the activity of pancreatic lipase, whereas the activities
of pancreatic trypsin, chymotrypsin, and amylase were significantly
enhanced by the same (Platel and Srinivasan, 2000a). When given as a
single oral dose, cumin exerted a lowering effect on pancreatic lipase,
amylase, trypsin, and chymotrypsin. Among the terminal digestive
enzymes, a small intestinal maltase activity was significantly higher in
animals fed with cumin, whereas lactase and sucrose were unaffected
(Platel and Srinivasan, 1996).
Dietary cumin had a significant stimulatory effect on bile flow
rate, the extent of increase in bile volume being 25 per cent, whereas
its single oral dose did not have any effect on bile secretion rate
(Platel and Srinivasan, 2000b). Dietary intake of cumin had a pro-
found influence on bile acid output (quantity secreted per unit time),
bile acid secretion being as high as 70 per cent over the control.
Similar significant increases in bile acid secretion were seen in the
case of cumin when administered as a single oral dose. Since bile
juice makes a significant contribution to the overall process of diges-
tion and absorption, essentially by supplying bile acids required for
micelle formation, it is expected that cumin, which has a digestive
stimulant action, could do so by stimulating biliary secretion of
bile acids.
Another study has examined whether this digestive stimulant
spice cumin also affects the duration of residence of food in the
gastrointestinal tract of experimental rats (Platel and Srinivasan,
2001). Cumin produced a significant shortening of the food transit
time by 25 per cent. The reduction in food transit time produced by
dietary cumin roughly correlates with their beneficial influence either
on digestive enzymes or bile secretion.
Antidiabetic effects
The antidiabetic effect of cumin seeds has been reported in human
diabetics (Karnick, 1991) (Table 2). In this study, 80 patients with
non-insulin dependent diabetes mellitus were orally administered for
24 weeks with an Ayurvedic formulation containing C.  cyminum.
Fasting and post-prandial blood sugar at 6-week intervals was
significantly reduced in all the patients. Dietary cumin seeds were
observed to alleviate diabetes-related metabolic abnormalities in
STZ-diabetic rats (Willatgamuwa et  al., 1998). An 8-week dietary
regimen containing cumin powder (1.25%) was found to be remark-
ably beneficial, as indicated by a reduction in hyperglycaemia and
4 K. Srinivasan, 2018, Vol. 2, No. 1

Table 1.  Differences between seed spices closely related to cumin seeds.

Common name of Cumin Black cumin (Nigella/kalonji) Bitter cumin (Kashmiri jeera/ Shahi jeera)
the spice

Scientific name Cuminum cyminum
Genus/family Cuminum/Apiaceae (member of
Parsley family)
Native of countries East Meditaranian to South Asia.
growing Now mostly grown in Pakistan, India,
Uzbekistan Iran, Turkey, Morocco,
Egypt, Syria, Chile, Mexico, and China
Traditional uses Both whole and ground seeds are used
in the cuisines of many cultures for
ages. It has also many uses in trad-
itional medicine. They are used in
Nigella sativa
Nigella/Ranunculaceae
South to Southwest Asia. Middle Eastern
Mediterranean region, South Europe,
Northern India, Pakistan, Syria, Turkey,
Iran, and Saudi Arabia
A spice in Indian and Middle Eastern
cuisines. In the ancient Egypt, it was
used as a preservative in mummification.
Traditionally, it is used for asthma, dia-
Cuminum nigrum or Bunium persicum
Cuminum/Apiaceae
Central Asia to Northern India.
Mountainous regions of North India
A spice in Northern Indian cookery, often
the Moghul cooking

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chronic diarrhoea and dyspepsia betes, hypertension, fever, inflammation,
bronchitis, dizziness, eczema, and gastro-
intestinal disturbances
Main constituents Cuminaldehyde Thymoquinone Cuminaldehyde, p-mentha-1,3-dien-7-al
and p-mentha-1,4-dien-7-al

Table 2.  Digestive stimulant and antidiabetic effects of Cumin seeds.

Model/system Effect observed Researcher

Digestive stimulant action

Wistar rats Dietary 1.25% cumin for 8 weeks significantly enhanced the activities of Platel and Srinivasan, 2000a
pancreatic trypsin, chymotrypsin, and amylase
Wistar rats Dietary 1.25% cumin for 8 weeks significantly enhanced the small Platel and Srinivasan, 1996
intestinal maltase activity
Wistar rats Dietary 1.25% cumin for 8 weeks had a significant stimulatory effect on Platel and Srinivasan, 2000b
bile flow rate and bile acid secretion
Wistar rats Dietary 1.25% cumin for 8 weeks reduced gastrointestinal food Platel and Srinivasan, 2001
transit time
Antidiabetic action
Human NIDDM subjects Fasting and post-prandial blood sugar was reduced when a formulation Karnick, 1991
consisting cumin was orally administered for 24 weeks
STZ-diabetic rats Dietary cumin seeds for 8 weeks were observed to alleviate Willatgamuwa et al., 1998
diabetes-related metabolic abnormalities
Alloxan-diabetic rats Hyperlipidemia associated with diabetes mellitus was also effectively Dandapani et al., 2002
countered by dietary cumin
Alloxan-diabetic rabbits Cuminum nigrum seeds or their methanol/water extracts were found to be Akhtar and Ali, 1985
hypoglycemic
Alloxan-diabetic rabbits The antihyperglycemic influence of Cuminum nigrum was produced by the Ahmad et al., 2000
fraction containing flavonoid compounds
Normal rabbits Oral administration of C. cyminum decreased the area under the glucose Roman-Ramos et al., 1995
tolerance curve and the hyperglycemic peak.
STZ-diabetic rats Methanolic extract of C. cyminum treated for 4 weeks mitigated oxidative Jagtap and Patil, 2010
stress and formation of AGEs
Sprague-Dawley rats Cuminaldehyde isolated from C. cuminum inhibited lens aldose reductase Lee, 2005
and α-glucosidase of rats

glucosuria. Hyperlipidemia associated with diabetes mellitus was
also effectively countered by dietary cumin in alloxan-diabetic rats
(Dandapani et al., 2002).
Cuminum nigrum seeds or their water or methanol extracts
have been observed to be hypoglycemic in alloxan-diabetic rab-
bits (Akhtar and Ali, 1985). The antihyperglycemic influence of
C. nigrum has been attributed to the flavonoid compounds present
in these seeds (Roman-Ramos et  al., 1995; Ahmad et  al., 2000).
Methanolic extract of C.  cyminum has been investigated in strep-
tozotocin-diabetic rats on diabetes, oxidative stress, and forma-
tion of advanced glycated end products (AGE) in comparison with
glibenclamide (Jagtap and Patil, 2010). In vitro studies indicated that
cumin inhibited free radicals and AGE formation. The antidiabetic
effect of cumin (treated for 4 weeks) was comparable to glibencla-
mide and even better in controlling oxidative stress and AGE forma-
tion, which is implicated in pathogenesis of diabetic microvascular
complications. The inhibitory activity of C. cyminum seed–isolated
component cuminaldehyde has been evaluated against lens aldose
reductase and α-glucosidase isolated from Sprague-Dawley rats and
compared with that of quercetin as an aldose reductase inhibitor and
acarbose as an α-glucosidase inhibitor (Lee, 2005). Cuminaldehyde
was about 1.8 and 1.6 times less in inhibitory activity than acarbose
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1  5

Table 3.  Cardioprotective, anti-inflammatory, and chemopreventive effects of cumin seeds.

Model/system Effect observed Researcher

Cardioprotective influence
Rat
Patients with
hypercholesterolemia
Anti-inflammatory effect
LPS-stimulated RAW 264.7 cells
Chemopreventive effect
Mice
Orally administered aqueous cumin extract (200 mg/kg body for 9 weeks) Kalaivani et al., 2013
improved plasma nitric oxide and decreased the systolic blood pressure in
hypertensive rats.
Cumin extract significantly decreased the level of oxLDL while increasing the Samani and Farrokhi, 2014
activities of paraoxonase, and arylesterase activities were increased in serum
Cumin essential oil exerted anti-inflammatory effects via inhibition of Wei et al., 2015
NF-κB and mitogen-activated protein kinases ERK and JNK
Dietary 2.5 and 5.0% cumin alleviated benzo(α)pyrene-induced Gagandeep et al. 2003
forestomach tumourigenesis and 3-MCA-induced uterine cervix tumorigenesis,

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attributable to its ability to modulate carcinogen metabolism
Rat Dietary cumin (1.25% for 32 weeks) suppressed DMH-induced colon Nalini et al., 2006
carcinogenesis. The excretion of fecal bile acids and neutral sterols was
increased.
HT29 colon cancer cells Spent cumin from Ayurvedic industry was effective in arresting the cell cycle Arun et al., 2016
and inducing apoptosis
Miscellaneous nutraceutical effects
PC12 cells C. cyminum essential oil inhibited the fibrillation of α-synuclein Morshedi et al., 2015
suggesting neuroprotective effects
Rat Aqueous extract of cumin seeds showed anti-diarrhoeal effect when induced Sahoo et al., 2014
with castor oil

and quercetin, respectively. Nonetheless, cuminaldehyde may be use-
ful for antidiabetic therapeutics.
Anti-inflammatory effects
Cumin essential oil was investigated for the anti-inflammatory effects
in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the
underlying mechanisms (Wei et al., 2015) (Table 3). Volatile constitu-
ents were identified in essential oil using Gas Chromatography - Mass
Spectrometry (GC-MS), the most abundant constituent being cumi-
naldehyde (48.8%). Cumin oil exerted anti-inflammatory effects in
LPS-stimulated RAW cells through inhibiting NF-κB and mitogen-
activated protein kinases suggesting its potential as an anti-inflam-
matory agent.
Cardio-protective influence through hypolipidemic
and hypotensive effects
Cuminum cyminum is traditionally used for the treatment of indigestion
and hypertension. The anti-hypertensive potential of aqueous extract
of cumin seed and its role in arterial–endothelial nitric oxide synthase
expression, inflammation, and oxidative stress have been evaluated in
renal hypertensive rats (Kalaivani et al., 2013) (Table 3). Cumin admin-
istered orally (200 mg/kg body) for 9 weeks improved plasma nitric
oxide and reduced the systolic blood pressure in hypertensive rats. This
was accompanied by the up-regulation of the expression of inducible
nitric oxide synthase (iNOS), Bcl-2, TRX1, and TRXR1 and down-
regulation of the expression of Bax, TNF-α, and IL-6. These data sug-
gest that cumin seeds augment endothelial functions and ameliorate
inflammatory and oxidative stress in hypertensive rats.
Paraoxanase-1 plays a protective role against the oxidative modi-
fication of plasma lipoproteins and hydrolyzes lipid peroxides in
human atherosclerotic lesions. Flavonoids present in cumin seeds
are recognized to have antioxidant activity and improve the antioxi-
dant system. A study demonstrated that cumin extract significantly
decreased the level of oxidized Low-density lipoprotein (OxLDL)
while increasing the activities of paraoxonase, and arylesterase activi-
ties were increased in serum (Samani and Farrokhi, 2014). The effect
of cumin added to normal and hypercholesterolemia inducing diet on
serum and liver cholesterol levels in rats has been studied (Sambaiah
and Srinivasan, 1991). Dietary cumin did not show any cholesterol
lowering effect when included in the diet (1.25%) at about 5-fold the
normal consumption level.
Chemopreventive effects
Cancer chemopreventive potentials of dietary 2.5 and 5.0 per cent
cumin were evaluated against benzo(α)pyrene-induced tumorigenesis
in forestomach and 3-methylcholanthrene (MCA)-induced tumorigen-
esis in uterine cervix in mice (Gagandeep et al., 2003) (Table 3). Cumin
produced a significant inhibition of stomach tumour. The effect on car-
cinogen/xenobiotic metabolizing phase I and phase II enzymes, antioxi-
dant enzymes, and lipid peroxidation in the liver was also examined.
Cytochrome P450 and cytochrome b5 were significantly augmented by
dietary cumin. The phase II enzyme glutathione-S-transferase (GST)
was increased by cumin, whereas the specific activities of superoxide
dismutase (SOD) and catalase were significantly elevated. Lipid peroxi-
dation was inhibited by cumin, suggesting that the cancer chemopre-
ventive potential of cumin could be attributed to its ability to modulate
carcinogen metabolism.
The effect of cumin (C. cyminum; dietary 1.25% for 32 weeks)
was studied on colon cancer induced in rats by 1,2-dimethylhydrazine
(DMH) s.c. 20 mg/kg of body weight (15 doses, at weekly intervals)
(Nalini et al., 2006). Results showed that cumin suppresses colon car-
cinogenesis in the presence of the procarcinogen DMH. The excretion
of fecal bile acids and neutral sterols was significantly increased in
cumin+DMH-administered rats. Cholesterol and 3-hydroxy-3-meth-
ylglutaryl-CoA reductase activity were decreased in cumin+DMH-
treated rats. Spent cumin generated from Ayurvedic industry was
evaluated for its nutraceutical potential in terms of antioxidant (in
terms of scavenging 2,2-Diphenyl-1-picryl-hydrazyl-hydrate [DPPH]
6 K. Srinivasan, 2018, Vol. 2, No. 1

Table 4.  Antidiabetic effects of black cumin (Nigella sativa) seeds.

Model/system Effect observed Researcher

STZ-diabetic rats
Rat pancreatic islets
STZ/NA-diabetic hamsters
STZ-diabetic hamsters
Hepatocytes (HepG2)
Diabetic rabbits
The oil of N. sativa significantly lowered blood glucose in STZ-diabetic El-Dakhakhny et al., 2002
rats after 2, 4, and 6 weeks
Defatted extract of N. sativa seed increased glucose induced insulin re- Rchid et al., 2004
lease from isolated rat pancreatic islets in vitro
N. sativa oil treatment for 4 weeks decreased blood glucose and Fararh et al., 2002
increased serum insulin
The hypoglycemic effect of N. sativa oil (400 mg/kg by p.o.) is partially Fararh et al., 2004
due to a decrease in hepatic gluconeogenesis
Defatted extract of N. sativa seeds increased glucose consumption by Yuan et al., 2014
hepatocytes (HepG2) in vitro through activation of AMPK
N. sativa extract (orally for 2 months) decreased lipid peroxidation and Meral et al., 2001
increased antioxidant defense system

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STZ-diabetic rats Daily oral administration of ethanol extract of N. sativa seeds Kaleem et al., 2006
(300 mg/kg for 30 days) reduced hyperglycemia and improved altered
levels of lipid peroxidation products and antioxidant enzymes in liver
and kidney
STZ-diabetic rats N. sativa oil (0.2 ml/kg for 30 days) decreased hyperglycemia and Kanter et al., 2003
restored lowered serum insulin with partial regeneration of pancreatic
β-cells
STZ-diabetic rats N. sativa treatment exerts a protective effect on diabetes by decreasing Kanter et al., 2004
oxidative stress and preserving pancreatic β-cell integrity
STZ-diabetic rats fed with Daily administration of N. sativa oil significantly induced the gene ex- Balbaa et al., 2016
high-fat diet pression of insulin receptor and upregulated the expression of
insulin-like growth factor-1
STZ-diabetic rats N. sativa seed oil down-regulated the expression of apoptotic markers Cüce et al., 2015
in the aortic medial layer of diabetic rats, thus preventing apoptosis in
vascular structures
STZ-diabetic rats Protective effects of N. sativa oil on insulin sensitivity and ultrastructural Kanter et al., 2009
changes of pancreatic β-cells
STZ-diabetic rats N. sativa extract, oil, and TQ decreased the diabetes-induced lipid Abdelmeguid et al., 2010
peroxides and hyperglycemia, and significantly increased serum insulin
and SOD activity in tissues
STZ-NA–induced diabetic rats Oral administration of TQ dose-dependently improved the glycemic Pari and Sankaranarayanan, 2009
status; levels of insulin and Hb increased; altered activities of
carbohydrate metabolizing enzymes were restored
Patients with diabetes N. sativa oil showed a beneficial effect on various clinical and Najmi et al., 2008
biochemical parameters of the insulin resistance syndrome
Patients with type 2 diabetes N. sativa (2 g/day) brought reductions in fasting blood glucose, post- Bamosa et al., 2010
prandially, and glycosylated haemoglobin.

radical), antidiabetic (in terms of better α-amylase inhibition and
glucose uptake activity in L6 cells), and anticancer properties (in
terms of arresting the cell cycle and inducing apoptosis in HT29
colon cancer cells) and compared with that of the raw cumin (Arun
et al., 2016). The results suggested that nutraceutical food formula-
tion made out of spent cumin could play a major role in the preven-
tion or management of degenerative diseases.
Miscellaneous nutraceutical effects
Cumin seeds are traditionally used for the treatment of diarrhoea.
The aqueous extract of cumin seeds (100, 250, and 500 mg/kg) has
been examined against diarrhoea in albino rats induced with castor
oil (Sahoo et  al., 2014). The extract showed significant inhibition
in the frequency of diarrhoea, delaying the defecation time, secre-
tion of intestinal fluid, and intestinal propulsion in a dose-dependent
manner. Fibrillation of α-synuclein (α-SN) is a critical process in the
pathophysiology of several neurodegenerative diseases, especially
Parkinson’s disease. A study on the inhibitory effects of C. cyminum
essential oil on the fibrillation of α-SN indicated that the small
abundant natural compound, cuminaldehyde can modulate α-SN
fibrillation, suggesting that such natural active aldehyde could have
potential therapeutic applications (Morshedi et al., 2015).
Health effects of N. sativa
Black cumin (N.  sativa) has been in use in traditional systems of
medicine for various medical disorders. Nigella sativa is used in
Moroccan folk medicine for the treatment of diabetes mellitus.
Many pre-clinical and clinical trials have investigated its efficacy,
using the seed oil, essential oil, and its isolated main constituent TQ
(Ali and Blunden, 2003). These investigations provide preliminary
support for its use in asthma, allergic rhinitis, and atopic dermatitis
(Yarnell and Abascal, 2011). Black cumin might help in dyspepsia,
respiratory problems, diabetes mellitus, and metabolic syndrome
(Yarnell and Abascal, 2011). A  meta-analysis of clinical trials sug-
gests that N. sativa has a short-term benefit in lowering systolic and
diastolic blood pressure, and its various extracts can reduce triglyc-
erides, LDL, and total cholesterol (Sahebkar et al., 2016a; 2016b).
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1  7

Table 5.  Anti-cancer effects of black cumin (Nigella sativa) seeds.

Model/system Effect observed Researcher

Mice—B()P-induced forestomach cancer
Rat—DMH-induced colon cancer
Rats—gastric ulcer induced by necrotiz-
ing agents
Wistar rats—colon cancer induced with
carcinogens
N. sativa extract ameliorated benz(a-)pyrene-induced carcinogenesis in Aruna and Sivarama-krishnan,
the forestomach 1990
Orally administered N.sativa oil (14 weeks) reduced the induction and Salim and Fukushima, 2003
development of 1,2-dimethylhydrazine-induced aberrant crypt foci
(ACF), putative preneoplastic lesions for colon cancer
N. sativa aqueous suspension significantly ameliorated the ulcer severity Al Mofleh et al., 2008
and basal gastric acid secretion. The anti-ulcer effect is possibly prosta-
glandin-
mediated and/or through its antioxidant and anti-secretory activities
1000 or 4000 ppm N. sativa volatile oil in the diet for 30 weeks signifi- Salim, 2010
cantly reduced malignant and benign colon tumour sizes, incidences and
multiplicities

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Rats—colitis induced with TNBS
Rat—DMBA-induced breast cancer
Children with acute lymphoblastic
leukaemia
Cancer cells
Cancer cells
Prostate cancer (PC-3) cell
MCF-7 cells
Human cervical squamous carcinoma
cells (SiHa)
Human osteosarcoma cell line SaOS-2
Breast cancer MDA-MB-231 cells
Pancreatic cancer cells
Panc-1 cells
PC-3 cells
Gastric cancer cells
Oral N. sativa oil, by preventing inflammatory status in the blood, partly Isik et al., 2011
protected colonic tissue against experimental ulcerative colitis
Orally administered (1—10 mg/kg) N. sativa oil or thymoquinone thrice Linjawi et al., 2015
in a week for 4 months exerted a protective effect against DMBA-induced
breast cancer
Black cumin seeds (80 mg/kg/day for 1 week) decreased methotrexane Hagag et al., 2015
hepatotoxicity and improved survival in children with leukaemia
Thymoquinone suppressed tumour cell proliferation in colorectal Gali-Muhtasib et al., 2006
carcinoma, breast adenocarcinoma, osteosarcoma, ovarian carcinoma,
myeloblastic leukaemia, and pancreatic carcinoma
TQ suppressed tumor cell proliferation in the case of breast adenocar- Allahghadri et al., 2010
cinoma, pancreatic carcinoma, colorectal carcinoma, ovarian carcinoma,
osteosarcoma, and myeloblastic leukaemia
TQ is shown to prevent tumour angiogenesis in a xenograft human Yi et al., 2008
cancer model
N. sativa lipid extract and aqueous extract exhibited cytotoxicity to Mahmoud and Torchilin, 2012
MCF-7 cells with LC50 of 2.7 and 50 mg/ml
TQ was with IC50 values of 10.7 µg/ml; elimination of SiHa cells via Ng et al., 2011
apoptosis with down-regulation of the Bcl-2 protein
Anti-tumour and anti-angiogenic activity of TQ possibly mediated by an Peng et al., 2013
inhibition of NF-κB and downstream effector molecules
TQ exerted a strong anti-proliferative effect on breast cancer cells via its Woo et al. 2011
potential effect on the PPAR-γ activation pathway; migration and
invasion were also reduced
Treatment with TQ down-regulated MUC4 expression and induced Torres et al., 2010
apoptosis; increased apoptosis, decreased motility, and decreased
migration of pancreatic cancer cells
TQ dose-dependently suppressed the migration and invasion of panc-1 Wu et al., 2011
cells by down-regulating NF-kB and MMP-9
Administration of N. sativa reduced the carcinogenic effects of DMBA in Shafi et al., 2008
mammary carcinoma
Pre-treatment with TQ significantly increased the apoptotic effects Lei et al., 2012
induced by 5-FU in gastric cancer cell lines in vitro

Several studies made in the last decades validate its health benefi-
cial effects particularly in diabetes, dyslipidemia, hypertension, and
obesity. A  systematic review of all human trials has revealed that
N. sativa supplementation might be effective in glycemic control in
humans (Mohtashami and Entezari, 2016).
Antidiabetic effects
Nigella sativa seeds are traditionally used in the management of dia-
betes mellitus in indigenous systems of medicine and folk remedies.
Defatted extract of N.  sativa seed is reported to increase glucose-
induced insulin release from isolated rat pancreatic islets in vitro
(Rchid et al., 2004) (Table 4). The effect of N. sativa extracts (defatted
fractions either containing acidic and neutral compounds or contain-
ing basic compounds) have been investigated on insulin secretion in
vitro in rat pancreatic islets in the presence of glucose (8.3 mmol/l).
Results showed that the antidiabetic properties of N.  sativa seeds
may partially be mediated by the stimulation of insulin release, espe-
cially by the basic subfraction of the seed. The possible insulinotropic
property of N.  sativa oil has also been studied in STZ plus nico-
tinamide (NA) induced diabetes mellitus in hamsters. Nigella sativa
oil treatment for four weeks decreased blood glucose and increased
serum insulin (Fararh et  al., 2002). Immunohistochemical staining
revealed the presence of insulin in the pancreas from N. sativa oil-
treated group, suggesting that the hypoglycemic effect results, at
least partly, from a stimulatory effect on β-cell function.
The oil of N. sativa significantly lowered blood glucose in STZ-
diabetic rats after 2, 4, and 6 weeks (El-Dakhakhny et  al., 2002).
A study of the effect of N. sativa oil on insulin secretion from iso-
lated rat pancreatic islets in the presence of glucose indicated that its
8 K. Srinivasan, 2018, Vol. 2, No. 1

Table 6.  Anti-inflammatory/analgesic effects and immunomodulatory property of black cumin (Nigella sativa) seeds.

Model/system Effect observed Researcher

Anti-inflammatory property and analgesic activity

Rats N. sativa essential oil produced a significant analgesic effect on acetic Hajhashemi et al., 2004
acid-induced writhing, formalin, and light tail flick tests
Rats Intraperitoneal injection of N. sativa oil from 100 to 400 µl/kg significantly Hajhashemi et al., 2004
inhibited carrageenan-induced paw oedema
BV-2 murine microglia cells TQ showed an effective anti-inflammatory effect on LPS-stimulated Taka et al., 2015
microglial cells
Human trials Anti-osteoporotic effects of N. sativa and TQ are evidenced by observing in- Shuid et al., 2012
hibition of inflammatory cytokines (interleukin-1 and 6) and the
transcription factor (NFκB)
Pancreatic ductal adenocar- TQ inhibited proliferation in these cells by inhibiting proinflammatory Chehl et al., 2009
cinoma (PDA) cells pathways; this anti-inflammatory potential involved modulation of the ex-

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pression of different pro-inflammatory cytokines and chemokines
Rats Oral administration of TQ (5 mg/kg body/day for 21 days) showed Umar et al., 2012
anti-arthritic activity by significantly reducing pro-inflammatory mediators
Immunomodulatory action
BALB/c mice and C57/BL6 Aqueous extract of N. sativa significantly enhanced the total white blood Ghonime et al., 2011
primary cells cells count and increased spleen weight in BALB/c mice and enhanced
splenocyte proliferation
Long-Evans rat Treatment with N. sativa oil significantly decreased the antibody production Torres et al., 2010
in response to typhoid vaccination
Pigeons Co-administration of N. sativa (2.5%) with oxytetracycline (OXT) Abel-Salam, 2012
completely blocked the decreasing effects on total leukocyte and lymphocyte
counts elicited by OXT and produced immunostimulant effects
Rats N. sativa oil showed a promising radioprotective action against Assayed, 2010
immunosuppressive and oxidative effects of γ-radiation
Mice N. sativa seed extract significantly improved symptoms and immune Duncker et al. 2012
parameters in murine OVA-induced allergic diarrhoea

hypoglycemic effect might be mediated by extra-pancreatic actions
rather than by stimulation of insulin release. The hypoglycemic
effect of N. sativa oil (400 mg/kg by p.o.) is partly due to decreased
hepatic gluconeogenesis (Fararh et al., 2004). Indazole-type alkaloid
17-O-(β-D-glucopyranosyl)-4-O-methyl nigellidine present in the
defatted extract of N.  sativa seeds increased glucose consumption
by hepatocytes (HepG2 cells) in vitro through activation of AMP-
activated protein kinase (AMPK) (Yuan et al., 2014).
Nigella sativa extract given orally for 2 months decreased lipid
peroxidation and increased antioxidant defence system and also
prevented the lipid peroxidation-induced liver damage in diabetic
rabbits (Meral et al., 2001). Daily oral administration of ethanol
extract of N.  sativa seeds (300  mg/kg) to STZ-diabetic rats for
30 days reduced the elevated levels of blood glucose, lipids, plasma
insulin, and improved altered levels of lipid peroxidation products
and antioxidant enzymes in liver and kidney (Kaleem et al., 2006).
This suggested that in addition to antidiabetic activity, N.  sativa
seeds may control diabetic complications through antioxidant
effects. Treatment of N.  sativa oil (0.2  ml/kg, i.p.) for 30  days
decreased the elevation in serum glucose and restored lowered
serum insulin with partial regeneration or proliferation of pancre-
atic β-cells in STZ-diabetic rats (Kanter et al., 2003). The possible
protective effects of N. sativa (0.2 ml/kg, i.p.) against β-cell damage
from STZ-diabetes in rats have been evidenced by the observed
decrease in lipid peroxidation and serum nitric oxide and increase
in the activities of antioxidant enzymes in the pancreas (Kanter
et  al., 2004). Increased staining for insulin and preservation of
β-cell numbers were evident in N.  sativa–treated diabetic rats.
This suggests that N. sativa treatment exerts a protective effect on
diabetes by decreasing oxidative stress and preserving pancreatic
β-cell integrity.
Nigella sativa oil administration (daily) to STZ-induced diabetic
rats maintained on a high-fat diet significantly induced the gene
expression of insulin receptor (Balbaa et  al., 2016). Nigella sativa
oil upregulated the expression of IGF-1 and phosphoinositide-3 kin-
ase, whereas the expression of ADAM-17 was downregulated. Also,
the N.  sativa oil significantly reduced blood glucose level, individ-
ual lipid profile, oxidative stress markers, serum insulin or insulin
receptor ratio, and the TNF-α, confirming that N. sativa oil has an
antidiabetic activity. Thus, the daily N. sativa oil treatment improves
insulin-induced signalling.
Hyperglycaemia is an important risk factor for the development
and progression of the macrovascular and microvascular complica-
tions that occur in diabetes. The expression of apoptotic markers in
the medial aortic layer of diabetic rats and the effects of N. sativa
seed oil on the expression of these markers have been investigated
(Cüce et al., 2015). It is understood that N. sativa seed oil is effective
against diabetes and merits further treatment strategies for prevent-
ing apoptosis in vascular structures.
Treatment of streptozotocin-diabetic rats with N. sativa extract,
N. sativa oil, and TQ, significantly decreased the diabetes-induced
lipid peroxides and hyperglycemia, and significantly increased
serum insulin and SOD activity in tissues. Nigella sativa oil and
TQ have therapeutic potential and are protective against STZ-
diabetes by decreasing oxidative stress, thus preserving pancreatic
β-cell integrity, leading to increased insulin levels (Abdelmeguid
et al., 2010). The protective effects of N. sativa oil on insulin sen-
sitivity and ultrastructural changes of pancreatic β-cells in STZ-
induced diabetic rats are reported (Kanter et al., 2009). It is evident
that N.  sativa treatment exerts a protective effect on diabetes by
decreasing morphological changes and preserving the pancre-
atic β-cell integrity (Kanter et  al., 2009). The anti-hyperglycemic
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1  9

Table 7.  Gastroprotectove, hepatoprotective, nephroprotective, and pulmonary-protective effects of black cumin (Nigella sativa) seeds.

Model/system Effect observed Researcher

Gastroprotective effect
Rats N. sativa (2.5 and 5.0 ml/kg)/TQ administration (10, 20, 50, and El-Abhar et al., 2003 and
100 mg/kg) exerted gastro-protection when subjected to Magdy et al., 2012
ischemia/reperfusion insult
Rats Anti-ulcer potential of N. sativa aqueous suspension on experimentally Al Mofleh et al., 2008
induced gastric ulcers (with various necrotizing chemicals) has been
evidenced
Hypothyroidal rats N. sativa and TQ protect gastric mucosa against the ulcerating effect of Khaled, 2009
alcohol
Newborn Sprague-Dawley rats N. sativa oil (2 ml/kg daily; i.p.) showed beneficial effect in rats with Tayman et al., 2012
necrotizing enterocolitis
Mice Treatment with TQ (5–25 mg/kg) ameliorated colonic inflammation in ex- Lei et al., 2012

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perimental inflammatory bowel disease (C57BL/6 murine colitis induced
with dextran sodium sulfate)
Nephroprotective effect
Rabbits Nephro-protective effect of N. sativa oil was observed against Saleem et al., 2012
gentamicin-associated nephrotoxicity
Rats Protective effect of N. sativa oil against methotrexate-induced Yaman and Balikci, 2010
nephrotoxicity
Rats Protective effects of N. sativa oil in the prevention of chronic cyclosporine Uz et al., 2008
A-induced nephrotoxicity by attenuation of the oxidative stress
Rats TQ supplementation prevented the development of gentamycin-induced de- Sayed-Ahmed and Nagi, 2007
generative changes in kidney tissues
Hepatoprotective effect
Rats N. sativa (0.2 ml/kg) relieves the deleterious effects of ischemia-reperfusion Yildiz et al., 2008
injury on the liver
Mice Pre-treatment with TQ (10 µmol/l) showed a significant protection on the Zafeer et al., 2012
hepatotoxicity of Cd++ particularly by relieving the depletion of
non-enzymatic and enzymatic antioxidants
Pulmonary protective effect
Wistar rats N. sativa treatment showed beneficial effects on experimental lung injury; Kanter, 2009
inhibited the inflammatory pulmonary responses
Rats N. sativa oil significantly reduced the severity of lung damage due to Tayman et al., 2012
hyperoxia
Patients with asthma N. sativa (15 ml/kg of 0.1 g% boiled extract for 3 months) significantly Boskabady et al., 2007
alleviated symptoms and frequency of asthma symptoms, chest wheezing,
and pulmonary function tests

potential of TQ and the effect on the activities of key enzymes of
carbohydrate metabolism in STZ-NA–induced diabetic rats have
been evaluated (Pari and Sankaranarayanan, 2009). Oral admin-
istration of TQ (20, 40, and 80  mg/kg body weight for 45  days)
dose-dependently improved the glycemic status in STZ/NA-induced
diabetic rats. The levels of insulin and haemoglobin increased along
with a decrease in glucose and HbA1c levels. The altered activities
of carbohydrate-metabolizing enzymes were also restored (Pari and
Sankaranarayanan, 2009).
In a clinical study, the adjuvant effect of N. sativa oil on vari-
ous clinical and biochemical parameters of the insulin resistance
syndrome in patients with diabetes and dyslipidemia has been evi-
denced (Najmi et  al., 2008). Nigella sativa accentuates glucose-
induced secretion of insulin besides negatively affecting glucose
absorption. Hence, it is of immense therapeutic benefit in diabetic
individuals (Kapoor, 2009). The effect of N. sativa seeds used as
an adjuvant therapy in addition to the anti-diabetic medications
on the glycemic control of patients with type 2 diabetes melli-
tus was investigated (Bamosa et  al., 2010). Nigella sativa at a
dose of 2 g/day caused significant reductions in fasting blood glu-
cose, 2-hour post-prandially, and glycosylated haemoglobin. The
results indicate that a dose of 2 g/day of N. sativa could serve as a
useful adjuvant to oral hypoglycemic drugs in patients with type
2 diabetes mellitus.
Ameliorative effects of N. sativa on dyslipidemia
Dyslipidemia is an established risk factor for ischemic heart disease.
Nigella sativa has been used for the treatment and prevention of hyper-
lipidemia (Asgary et  al., 2015). Different preparations of N.  sativa
including seed powder (100 mg–20  g daily), seed oil (20–800  mg
daily), TQ (3.5–20 mg daily), and methanolic extract reduced plasma
levels of total cholesterol, low-density lipoprotein cholesterol, and tri-
glycerides. In clinical trials, N. sativa was found to be effective when
added as an adjunct to conventional hypolipidemic and antidiabetic
medications. Inhibition of dietary cholesterol absorption, decreased
hepatic cholesterol synthesis, and up-regulation of LDL receptors
contribute to lipid-lowering effects of N. sativa. Overall, the evidence
from an experimental and a clinical study suggests that N. sativa seeds
are promising natural therapy for patients with dyslipidemia.
Anti-inflammatory property and analgesic activity
The antinociceptive and anti-inflammatory effects of TQ (Table 6),
supporting the common perception of N. Sativa as a potent analgesic
10
and anti-inflammatory agent, have been recently reviewed (Amin
and Hosseinzadeh, 2016). Many protective properties are attributed
to radical scavenging activity as well as an interaction with molecu-
lar targets involved in inflammation (proinflammatory enzymes and
cytokines). Further investigations are needed to understand the pre-
cise mechanisms responsible for the antinociceptive and anti-inflam-
matory effects of its active constituents.
Development of solid tumour malignancies is closely associated
with inflammation. The steam-distilled essential oil of N.  sativa,
which mainly contains p-cymene (37.3%) and TQ (13.7%), investi-
gated for its analgesic and antiinflammatory properties in rats was
found to produce a significant analgesic effect on acetic acid-induced
writhing, formalin, and light tail flick tests (Hajhashemi et  al.,
2004). Intraperitoneal injection of 100, 200, and 400 µl/kg signifi-
cantly inhibited carrageenan-induced paw oedema. Mechanism(s)
other than opioid receptors are believed to be involved in this an-
algesic effect of the Nigella essential oil. Its administration showed
anti-inflammatory activity probably attributable to TQ, one of the
major components of black cumin. The anti-inflammatory effect
of TQ on LPS-stimulated BV-2 murine microglia cells has been
reported, wherein TQ was effective in reducing nitrate with parallel
decline of iNOS protein expression evidenced (Taka et al., 2015). TQ
also reduced LPS-mediated elevation in gene expression of Cxcl10
and some of other cytokines. The anti-inflammatory properties of
TQ in LPS-activated microglial cells suggested the applicability of
TQ in delaying the onset of inflammation-mediated neurodegenera-
tive disorders.
The aqueous extract of N.  sativa has been found to pos-
sess anti-inflammatory and analgesic activities in animal models.
Although osteoporosis is linked to oxidative stress and inflamma-
tion, the anti-osteoporotic effects of N. sativa and TQ are evidenced
by observing the inhibition of inflammatory cytokines (interleukin
(IL)-1 and 6)  and the transcription factor (NFκB). Both N.  sativa
and TQ have shown potential as an anti-osteoporotic agent (Shuid
et  al., 2012). TQ induced apoptosis and inhibited proliferation in
pancreatic ductal adenocarcinoma (PDA) cells. This anti-inflam-
matory potential involved an effect on the expression of different
proinflammatory cytokines and chemokines. TQ dose-dependently
reduced PDA cell synthesis of MCP-1, TNF-α, IL-1β, and Cox-2.
TQ as an inhibitor of proinflammatory pathways provides an ef-
fective strategy that combines anti-inflammatory and proapoptotic
modes of action (Chehl et al., 2009). A clinical trial was conducted
to investigate the anti-inflammatory effects of N. sativa in patients
with allergic rhinitis symptoms. The anti-allergic effects of N. sativa
components could be attributed to allergic rhinitis (Nikakhlagh
et  al., 2011). The anti-arthritic activity of orally administered TQ
(5 mg/kg body once daily for 21 days) in collagen-induced arthritic
Wistar rats was evidenced with significantly reduced proinflamma-
tory mediators [IL-1β, IL-6, TNF-α, IFN-γ, and PGE2] and increased
IL-10 (Umar et al., 2012).
Immunomodulatory action
The immunomodulatory properties of N. sativa and its major active
ingredient, TQ in terms of their experimentally documented abil-
ity to modulate cellular and humoral adaptive immune responses
(Table  6) have comprehensively been reviewed (Majdalawieh and
Fayyad, 2015). The molecular and cellular mechanisms underlying
such immunomodulatory effects of N. sativa and TQ are highlighted,
and the signal transduction pathways implicated in the immunoreg-
ulatory functions are suggested. Experimental evidence suggests that
N.  sativa extracts and TQ can therapeutically be employed in the
K. Srinivasan, 2018, Vol. 2, No. 1
regulation of immune reactions in infectious and non-infectious con-
ditions such as allergy, autoimmunity, and cancer.
The potential immunomodulatory effects of aqueous extract of
N.  sativa investigated in BALB/c mice and C57/BL6 primary cells
with respect to splenocyte proliferation, macrophage function, and
anti-tumor activity demonstrated that N. sativa significantly enhances
splenocyte proliferation in a dose-responsive manner (Ghonime
et al., 2011). Aqueous extract of N. sativa significantly suppressed
the secretion of key proinflammatory mediators (IL-6, TNF-α, and
NO) by primary macrophages indicating anti-inflammatory effects
in vitro. Nigella sativa methanolic extract treatment (intraperito-
neal) enhanced the total white blood cells count and increased spleen
weight in BALB/c mice, suggesting the immunomodulatory activity
of N. sativa seeds (Ghonime et al., 2011). Treatment with N. sativa
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oil significantly decreased the antibody production in response to ty-
phoid vaccination (antigen typhoid TH) in a Long-Evans rat model.
These results indicated that the N. sativa seeds could be considered
as a potential immunosuppressive cytotoxic agent (Torres et  al.,
2010). Co-administration of N. sativa (2.5%) with oxytetracycline
completely blocked the leukocyte and lymphocyte decreasing effects
elicited by oxytetracycline and produced immunostimulant effects
in pigeons indicating an immune-protective effect (Abel-Salam,
2012). Nigella sativa oil is also shown to have a promising radio-
protective action against immunosuppressive and oxidative effects
of γ-radiation in rats (Assayed, 2010). Nigella sativa seed extract
significantly improved symptoms and immune parameters in murine
ovalbumin-induced allergic diarrhoea in mice (Duncker et al., 2012).
Antioxidant and antimicrobial activity
An evaluation of the essential oil of N.  sativa seeds, for antioxi-
dants, showed that TQ and other components (carvacrol, t-anet-
hole, and 4-terpineol) have a radical scavenging property. These
constituents and the essential oil showed variable antioxidant ac-
tivity when tested in the diphenylpicrylhydrazyl assay; they also ef-
fectively scavenged OH radical in the assay for non-enzymatic lipid
peroxidation.
TQ has been shown to suppress the ferric nitrilotriacetate-
induced oxidative stress in Wistar rats (Khan and Sultana, 2005).
Dietary N. sativa seeds inhibited the oxidative stress caused by oxi-
dized corn oil in rats (Al-Othman et  al., 2006). Dietary N.  sativa
(10%) neutralized the oxidative stress induced by hepatocarcinogens
such as dibutylamine and sodium nitrate in albino rats by normal-
izing glutathione and nitric oxide levels (Gendy et  al., 2007). The
N. sativa seed oil and TQ (intraperitoneal) are shown to have pro-
tective effects on lipid peroxidation process during ischemia-reperfu-
sion injury in rat hippocampus (Hosseinzadeh et al., 2007). Treating
broiler chicks with N.  sativa seed for 6 weeks reduced the oxida-
tive stress in the liver by increasing the activities of myeloperoxi-
dase, glutathione-S-transferase, CAT, adenosine deaminase, and by
decreasing hepatic lipid peroxidation (Sogut et al., 2008). The TQ
pre-treatment countered the increased level of lipid peroxidation and
augmented the antioxidant enzyme activities in the erythrocyte dur-
ing 1,2-dimethylhydrazine-induced colon carcinogenesis in Wistar
rats (Harzallah et al., 2012).
The bioactive compounds of N.  sativa essential oil identified
using GC and GC-MS included p-cymene, TQ, α-thujene, longi-
folene, β-pinene, α-pinene, and carvacrol. Nigella sativa essential
oil exhibited different biological activities including antifungal,
antibacterial, and antioxidant potentials. Nigella sativa essential oil
completely inhibited different Gram-negative and Gram-positive
bacteria (Morsi, 2000). Nigella sativa oil also exhibited stronger
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1 
radical scavenging activity against DPPḢ radical in comparison with
synthetic antioxidants.
Anti-cancer properties
The anti-cancer effect of N.  sativa has extensively been studied in
different in vitro and in vivo models (Table 5). Nigella sativa is able
to exert antioxidant, anti-mutagenic, cytotoxic, pro-apoptotic, anti-
proliferative, and anti-metastatic effects in various primary cancer
cells and cancer cell lines (Majdalawieh and Fayyad, 2016). The avail-
able studies strongly suggest that N. sativa could serve as an effective
agent to control tumour initiation, growth, and metastasis independ-
ently or in combination with conventional chemotherapeutic drugs.
Nigella sativa extract ameliorated the benz(α-)pyrene-
induced carcinogenesis in the forestomach in mice (Aruna and
Sivaramakrishnan, 1990). This is partly attributed to the ability to
influence phase II enzymes. Orally administered N.  sativa oil (14
weeks) interfered with the induction of aberrant crypt foci (ACF)
by 1,2-dimethylhydrazine, putative preneoplastic lesions for colon
cancer in rats (Salim and Fukushima, 2003). This inhibition may be
associated, in part, with the suppression of cell proliferation in the
colonic mucosa. Nigella sativa aqueous suspension significantly pre-
vented gastric ulcer formation experimentally induced by necrotiz-
ing agents and also significantly ameliorated the severity of ulcer
and gastric acid secretion in pylorus-ligated Shay rats (Al Mofleh
et al., 2008).
The chemopreventive potential of N.  sativa oil on tumour for-
mation has been revealed in a study using a rat multiorgan carcino-
genesis model induced by five different carcinogens (Salim, 2010).
Post-initiation administration of 1000 or 4000 ppm N. sativa vola-
tile oil in the diet for 30 weeks significantly reduced colon tumour
sizes, incidences, and multiplicities. Nigella sativa volatile oil also
significantly decreased the incidences and multiplicities of tumours
in the lungs and alimentary canal (particularly the oesophagus and
forestomach). Thus, N. sativa exerts potential inhibitory effects on
tumour development in multiple organ sites (Salim, 2010). Nigella
sativa oil (orally administered for 3 days) decreased the proinflam-
matory cytokines (TNF-α, IL-1β, and IL-6) in the blood of rats with
experimental colitis induced with trinitrobenzene sulfonic acid (Isik
et  al., 2011). Nigella sativa oil, by preventing inflammatory status
in the blood, partly protected colonic tissue against experimental
ulcerative colitis. Oral TQ (1–10  mg/kg) or N.  sativa oil (thrice
in a week for 4  months) exerted a protective effect against breast
cancer in female rats induced by 7,12-dimethylbenz[α-]anthracene
as revealed by tumour markers, histopathological alterations, and
the regulation of several genes (Brca1, Brca2, Id-1, and P53 muta-
tion) related to breast cancer (Linjawi et al., 2015).
Acute lymphoblastic leukaemia (ALL) is a common childhood
malignancy and is conventionally treated with methotrexate which
also produces hepatotoxicity. The therapeutic value of N. sativa oil
in methotrexate-induced hepatotoxicity has been assessed in 40
Egyptian children with ALL under methotrexate therapy (Hagag
et al., 2015). Nigella sativa oil (80 mg/kg/day for 1 week) produced
significant differences in remission, relapse, death, and disease-free
survival. Nigella sativa seeds decreased methotrexate hepatotoxicity
and improved survival. This report is suggestive of its application as
an adjuvant drug in patients under methotrexate therapy.
Nigella sativa seed oil and TQ have been understood to exert
antioxidant and chemopreventive properties (Allahghadri et  al.,
2010). TQ could suppress tumour cell proliferation in the case of
breast adenocarcinoma, pancreatic carcinoma, colorectal carcin-
oma, osteosarcoma, ovarian carcinoma, and myeloblastic leukaemia
(Allahghadri et al., 2010). The cancer chemopreventive ability of TQ
11
has been explained by its ability to modulate cell division in can-
cer cells, involving downregulation of Bcl-xL, cyclin D1, and VEGF
(Aggarwal et al., 2008). TQ is reported to be effective in inhibiting
human umbilical vein EC migration and invasion, suggesting its role
in angiogenesis (Gali-Muhtasib et al., 2006). TQ is shown to prevent
tumour angiogenesis in a xenograft human prostate cancer (PC-3)
model (Yi et  al., 2008). Nigella sativa, its oil, and TQ are effect-
ive against cancer in the blood system, lung, kidney, liver, prostate,
breast, cervix, and skin. Some studies attribute the anti-cancer effect
of TQ to its role as an antioxidant, ability to improve body’s immune
system, and ability to induce apoptosis and control Akt pathway
(Khan et al., 2011).
The cytotoxic effects of N.  sativa seed extract as an adjuvant
therapy to doxorubicin on human MCF-7 breast cancer cells are
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reported. Nigella sativa lipid extract was found to be cytotoxic to
MCF-7 cells with LC50 of 2.7  mg/ml, whereas its aqueous extract
exhibited cytotoxicity at about 50 mg/ml (Mahmoud and Torchilin,
2012). TQ was found to be cytotoxic to human cervical squamous
carcinoma cells (SiHa) with IC50 values of 10.7 µg/ml as determined
by MTT assay, whereas it was less cytotoxic towards the normal cells.
Cell cycle analysis indicated induction of apoptosis by the compound
and elimination of SiHa cells via apoptosis with down-regulation
of the Bcl-2 protein (Ng et al., 2011). An investigation of the anti-
tumour and anti-angiogenic effects of TQ on osteosarcoma in vitro
and in vivo showed that TQ induced higher growth inhibition and
apoptosis in the human osteosarcoma cell line SaOS-2. TQ signifi-
cantly blocked human umbilical vein endothelial cell tube formation
in a dose-dependent manner. The anti-tumour and anti-angiogenic
activity of TQ in osteosarcoma is possibly mediated by inhibition of
NF-κB and downstream effector molecules (Peng et al., 2013).
TQ exerted a strong anti-proliferative effect in breast cancer cells
via its potential effect on the PPAR-γ activation pathway, and in
combination with doxorubicin and 5-fluorouracil, TQ’s cytotoxicity
was found to be increased. Migration and invasion of MDA-MB-231
cells were also reduced by TQ, which was found to increase PPAR-γ
activity and down-regulate the expression of Bcl-2, Bcl-xL, and sur-
vivin in breast cancer cells (Woo et  al., 2011). An investigation of
the effect of TQ on pancreatic cancer cells and on MUC4 expres-
sion revealed down-regulated MUC4 expression and induced apop-
tosis in pancreatic cancer cells. The decrease in MUC4 expression
was accompanied by increased apoptosis, decreased motility, and
decreased migration of pancreatic cancer cells (Torres et al., 2010).
The administration of N. sativa reduced the carcinogenic effects
of DMBA in mammary carcinoma which indicated its protective
role in mammary carcinoma (Shafi et al., 2008). TQ dose-depend-
ently suppressed the migration and invasion of Panc-1 cells. TQ
also significantly down-regulated NF-kB and MMP-9 in Panc-1
cells. Administration of TQ significantly reduced tumour metasta-
sis. Furthermore, the expression of NF-kB and MMP-9 protein in
tumour tissues was down-regulated after treatment with TQ, thus
exerting anti-metastatic activity on pancreatic cancer both in vitro
and in vivo (Wu et al., 2011). The chemo-sensitizing effect of TQ and
5-fluorouracil (5-FU) on gastric cancer cells both in vitro and in vivo
is reported (Lei et  al., 2012). Pre-treatment with TQ significantly
increased the apoptotic effects induced by 5-FU in gastric cancer cell
lines in vitro. The combined treatment of TQ with 5-FU was more
effective in anti-tumour action than either of them individually in a
xeno-graft tumour mouse model. The TQ/5-FU-combined treatment
induces apoptosis by enhancing the activation of both caspase-3 and
caspase-9 in gastric cancer cells (Lei et al., 2012).
In summary, N. sativa oil and TQ are found to inhibit experimen-
tal carcinogenesis in different animal models. It has been shown to
12
arrest the growth of various cancer cells in culture as well as xeno-
graft tumours in vivo. The mode of anticancer effects of TQ includes
inhibition of carcinogen-metabolizing enzyme activity and oxidative
damage to cellular macromolecules, amelioration of inflammation,
inhibition of cell cycle and apoptosis in tumour cells, inhibition of
tumour angiogenesis, and suppression of migration, invasion, and
metastasis of cancer cells. TQ improves anti-cancer effects when
combined with conventionally used chemotherapeutic agents. At the
molecular level, TQ targets intracellular signalling pathways, par-
ticularly a variety of kinases and transcription factors, which are
activated during tumourigenesis.
Gastroprotective effect
Nigella sativa oil and its constituents are proved to exert gastro-
protective effect (Table 7); some of the potential mechanisms exhib-
ited by N. sativa in preventing or curing gastric ulcers are reviewed
recently (Khan et  al., 2016). The mechanism of gastroprotective
effect of TQ has been assessed in rats injected with TQ (10 and
20  mg/kg) and subsequently subjected to ischemia or reperfusion
insult. TQ restored the altered acid secretion, gastric mucosal con-
tent, lipid peroxide, and the activity of myeloperoxidase, reduced
glutathione, and total nitric oxide along with ulcer index, the effi-
cacy being comparable with that of the reference drug omeprazole.
TQ exerted gastroprotection via inhibiting proton pump, acid secre-
tion and neutrophil infiltration, while enhancing mucin secretion,
and nitric oxide production, in addition to the antioxidant influences
(Magdy et al., 2012).
The anti-ulcer potential of N. sativa aqueous suspension on gas-
tric ulcers experimentally induced with various noxious chemicals
(indomethacin, 80% ethanol, and 0.2 M NaOH) in Wistar rats
was examined (Al Mofleh et al., 2008). Nigella sativa significantly
prevented gastric ulcer formation induced by necrotizing agents by
significantly replenishing the depleted gastric wall mucus content
and gastric mucosal non-protein sulfhydryl concentration. The anti-
ulcer effect of N.  sativa was exerted through its antioxidant and
anti-secretory activities (Al Mofleh et al., 2008). Both N. sativa (2.5
and 5.0 ml/kg, p.o.) and TQ (5, 20, 50, and 100 mg/kg, p.o.) were
found to possess gastro-protective activity against gastric mucosal
injury induced by ischemia or reperfusion in Wistar rats (El-Abhar
et al., 2003). Lipid peroxidation and lactate dehydrogenase, elevated
by the ischemia or reperfusion insult and decreased glutathione and
activity of SOD accompanied by an increased formation of gastric
lesions, were countered by N.  sativa or TQ treatment, indicating
their gastroprotective effect, probably by conservation of the gastric
mucosal redox state.
Nigella sativa and TQ are reported to protect gastric mucosa
against the ulcerating effect of alcohol on hypothyroidal rats and
mitigate most of the biochemical adverse effects on gastric mucosa,
viz., increase in lipid peroxidation and reduced gastric glutathione
content, and enzyme activities of gastric SOD and GST (Khaled,
2009). The beneficial effect of N.  sativa oil (2  ml/kg daily, i.p.)
in rats with necrotizing enterocolitis (NEC) was studied in new-
born Sprague-Dawley rats (Tayman et al., 2012). Histopathologic
and apoptosis evaluation indicated that the bowel damage was less
severe in the N. sativa oil–treated group. Nigella sativa oil had a
beneficial preserving effect on tissue antioxidant enzymes, whereas
lipid peroxide levels were significantly lower than those in the NEC
control group. In a mouse model of inflammatory bowel disease
(C57BL/6 murine colitis induced with dextran sodium sulfate),
treatment with TQ (5, 10, or 25 mg/kg) ameliorated colonic inflam-
mation (Lei et al., 2012). The treatment of mice with TQ prevented
K. Srinivasan, 2018, Vol. 2, No. 1
and reduced the occurrence of diarrhoea and body weight loss,
associated with amelioration of colitis-related damage. Also, there
was a significant reduction in colonic myeloperoxidase activity and
malondialdehyde levels and an increase in glutathione levels (Lei
et al., 2012).
Nephroprotective effect
The nephroprotective effect of N.  sativa oil is observed in gen-
tamicin-induced nephrotoxicity in rabbits (Saleem et  al., 2012)
(Table 7). Vitamin C and N.  sativa oil when given as combination
showed a synergistic nephroprotective effect (Saleem et  al., 2012).
Oral treatment of N.  sativa oil (0.5, 1.0, or 2.0  ml/kg/day for
10  days) produced a dose-dependent amelioration of gentamycin-
induced nephrotoxicity in rats as assessed by the biochemical and
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histological indices of nephrotoxicity (Ali, 2004). The protective
effect of N. sativa oil on methotrexate-induced nephrotoxicity has
been reported in albino rats which is medicated through restoring
the antioxidant status (Abul-Nasr et al., 2001; Yaman and Balikci,
2010). The protective effects of N.  sativa oil in the prevention of
chronic cyclosporine A-induced nephrotoxicity in rats were evi-
denced by attenuation of the oxidative stress (Uz et al., 2008). TQ
supplementation prevented the development of gentamycin-induced
degenerative changes in kidney tissues and cisplatin-induced renal
injury in rats as indicated by lipid peroxides and renal organic anion
and cation transporters (Sayed-Ahmed and Nagi, 2007; Ulu et al.,
2012). Nigella sativa significantly prevented renal ischemia- or rep-
erfusion-induced functional and histological injuries in Wistar rats
(Mousavi, 2015). Nigella sativa showed protective effects against
ischemia-perfusion damage on kidney tissue based on the total anti-
oxidant capacity, oxidative status index, and activities of catalase
and myeloperoxidase in the kidney tissue (Yildiz et al., 2010).
Hepatoprotective effect
It is reported that N.  sativa (i.p.  0.2  ml/kg) relieves the deleterious
effects of ischemia-reperfusion injury on liver in rats, as indicated by
titers of marker enzymes, total antioxidant capacity, total oxidative
status, and myeloperoxidase in the liver tissue (Yildiz et  al., 2008)
(Table 7). The protective effect of TQ on the Cd++-induced hepato-
toxicity in mice, particularly the perturbation of non-enzymatic and
enzymatic antioxidants, has been reported (Zafeer et al., 2012). Pre-
treatment with TQ (10  µmol/l) showed a significant protection as
indicated by an attenuation of protein oxidation and recovery of the
depleted antioxidants, suggesting that TQ exerts modulatory influence
on the antioxidant defence system when subjected to toxic insult.
Pulmonary-protective activity and anti-asthmatic
effects
Nigella sativa has been investigated for the possible beneficial
effects on experimental lung injury in rats after pulmonary aspir-
ation (Kanter, 2009) (Table 7) and found that N.  sativa treatment
inhibits the inflammatory pulmonary responses. Nigella sativa ther-
apy resulted in a significant reduction in the activity of iNOS and
an increase in surfactant protein D in the lung tissue of different
pulmonary aspiration models. It is concluded that N.  sativa treat-
ment might be beneficial in lung injury that merits potential clinical
use. The ameliorative effect of N. sativa oil in rats with hyperoxia-
induced lung injury has also been reported (Tayman et al., 2012).
The prophylactic effect of an extract of N.  sativa (15  ml/kg of
0.1 g% boiled extract for 3 months) has been examined in asthmatic
adults. All asthma symptoms, the frequency of symptoms, chest wheez-
ing, and pulmonary function tests (PFT values) were significantly
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1 
improved as a result of N.  sativa treatment, generally suggesting a
prophylactic effect on asthma disease (Boskabady et  al., 2007). TQ
potently and dose-dependently inhibited the formation of leukot-
rienes—supposedly important mediators in asthma and inflammatory
processes, in human blood cells (Mansour and Tornhamre, 2004).
Miscellaneous nutraceutical effects
During the last three decades, several in vitro and in vivo animal
studies have ascertained the pharmacological properties of N. sativa,
including its antioxidant, antibacterial, anti-proliferative, proa-
poptotic, anti-inflammatory, and antiepileptic properties, and its
beneficial effect in conditions of atherogenesis, endothelial dys-
function, glucose dyshomeostasis, and disrupted lipid metabolism.
Nigella sativa and its constituents are found to have antioxidant,
antidiabetic, anti-inflammatory, and anti-tumour properties as well
as therapeutic effects on metabolic syndrome, and gastrointestinal,
neuronal, cardiovascular, and respiratory disorders in clinical trials
(Gholamnezhad et al., 2016). Experimental and clinical studies have
evidenced therapeutic effects of N. sativa seed extracts, oil, and TQ
on different disorders. Standard clinical trials are however needed for
N. sativa supplementation for its promotion as an adjuvant therapy.
Long-term administration of N. sativa increased brain serotonin
levels and improved learning ability and memory in rats (Perveen
et al., 2008). Chronic administration of N. sativa decreased sero-
tonin turnover and produced anxiolytic effects in rats. Tryptophan
concentration in brain and plasma also increased significantly fol-
lowing repeated oral administration of N. sativa oil, suggesting that
this oil is useful for the treatment of anxiety (Perveen et al., 2009).
Anti-anxiety-like effects of TQ (20 mg/kg) was observed in mice,
which involved modulation of GABA and NO levels. The anxiolytic
effect was accompanied by a significant decrease in plasma nitrite
and countering of decreased γ-aminobutyric acid content in the
brain (Gilhotra and Dhingra, 2011). The neuroprotective effects of
the aqueous extract of N. sativa have been recorded during cere-
bral ischemia in rats; this could be resulting from its free radical
scavenging, antioxidant (elevation in reduced glutathione, SOD, and
catalase (CAT) activities), and anti-inflammatory properties (Akhtar
et al., 2012).
The incidence of kidney stone may increase the vulnerability of
patients to renal failure. Nigella sativa and its main bioactive com-
ponent—TQ showed positive effects on the prevention or dissol-
ution of kidney stones and renal failure. This involves antioxidative,
anti-inflammatory, and immunomodulatory effects. Thus, N. sativa
and its components are beneficial in the prevention and curing of
nephrolithiasis and renal damages (Hayatdavoudi et al., 2016).
Conclusions
A number of therapeutic influences of N. sativa and TQ have been
scientifically investigated. This includes antidiabetic, anti-allergic,
anti-microbial, immune-modulatory, anti-inflammatory, and anti-
tumour effects (Figure 4). Nigella sativa and TQ also possess gastro-
protective, hepatoprotective, nephroprotective, and neuroprotective
activities. The scientific studies conducted so far have confirmed
the pharmacological potential of N.  sativa seeds, its oil, extracts,
and its active principles, particularly TQ. TQ is the most abundant
constituent of the volatile oil of N.  sativa seeds, and most of the
medicinal properties of N. sativa are attributable mainly to TQ. All
the available evidence suggests that TQ should be developed as a
drug or adjuvant in clinical trials. Nigella sativa seeds, its oil, and
13
constituents like TQ could be used in suitable combinations with
conventional therapeutic agents for maximizing the effectiveness in
the treatment of many infectious diseases and also to circumvent the
drug resistance problem. Further investigations are recommended to
explore the specific cellular and molecular targets of various con-
stituents of N. sativa, particularly TQ.
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