Cumin (Cuminum Cyminum) and Black Cumin

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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

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(Nigella sativa) seeds: traditional uses, chemical
constituents, and nutraceutical effects
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: [email protected]
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 K. Srinivasan, 2018, Vol. 2, No. 1

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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- Bunium persicum (occasionally referred to as Cuminum nigrum;
ter taste and aroma and are used as a spice in Indian and extensively in also known as Shahi jeera), belonging to Apiaceae (parsley family),
Middle Eastern cuisines. The dry-roasted nigella seeds flavour curries, is a smaller variety of cumin with a different flavour, popularly used
vegetables, and pulses. Black seeds are used in food as a flavouring in North Indian, Pakistani, and Iranian foods (Figure 1). Until now,
additive in breads and pickles. It is also used as an ingredient of the there is only very little scientific information on this spice.
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 Chemical constituents
long history of use as medicine in the Indian traditional system of medi- Cumin seeds are nutritionally rich; they provide high amounts of fat
cine like Unani and Ayurveda (Sharma et al., 2005). The black cumin (especially monounsaturated fat), protein, and dietary fibre. Vitamins
seeds have traditionally been used in the Southeast Asian and Middle B and E and several dietary minerals, especially iron, are also con-
East countries for the treatment of diseases such as asthma, bron- siderable in cumin seeds. Cuminaldehyde (Figure 2), cymene, and
chitis, rheumatism, and other inflammatory diseases. Nigella sativa terpenoids are the major volatile components of cumin (Bettaieb
has extensively been used because of its therapeutic potential and pos- et al., 2011). Cumin has a distinctive strong flavour. Its warm aroma
sesses a wide spectrum of activities, namely, diuretic, antihypertensive, is due to its essential oil content. Its main constituent of aroma com-
antidiabetic, anticancer, immune-modulatory, antimicrobial, anthel- pounds are cuminaldehyde and cuminic alcohol. Other important
mintic, analgesic and anti-inflammatory, spasmolytic, bronchodilator, aroma compounds of roasted cumin are the substituted pyrazines,
gastroprotective, hepatoprotective, and renal protective properties. 2-ethoxy-3-isopropylpyrazine, 2-methoxy-3-sec-butylpyrazine, and
Traditionally, seeds of N. sativa are widely used for asthma, diabetes, 2-methoxy-3-methylpyrazine. Other components include γ-terpinene,
hypertension, fever, inflammation, bronchitis, dizziness, rheumatism, safranal, p-cymene, and β-pinene (Li and Jiang, 2004).
skin disorders, and gastrointestinal disturbances (Table 1). It is also Nigella sativa seeds contain protein (26.7%), fat (28.5%), carbohy-
used as a liver tonic, digestive, antidiarrhoeal, emmenagogue, and to drates (24.9%), crude fibre (8.4%), and total ash (4.8%). Nigella sativa
control parasitic infections and boost immune system (Goreja, 2003). seeds also contain a good amount of various vitamins and minerals
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1  3

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Figure 4.  Multiple medicinal properties of Nigella sativa (black cumin seeds).

like Cu, P, Zn, and Fe. Many active compounds have been identified in whether they have any stimulatory effect on the digestive enzymes.
N. sativa. The most important active compounds of N. sativa are thy- The influence of cumin seeds on the digestive enzymes of the rat pan-
moquinone (TQ) (30%–48%) (Figure 2), thymohydroquinone, dithy- creas and intestinal mucosa has particularly been investigated as a
moquinone (nigellone), p-cymene (7%–15%), carvacrol (6%–12%), result of both continuous dietary intake and single oral administra-
4-terpineol (2%–7%), t-anethole (1%–4%), sesquiterpene longifolene tion (Platel and Srinivasan, 1996; 2000a) (Table 2). Dietary (1.25%)
(1%–8%), α-pinene, and thymol. (Boskabady and Shirmohammadi, cumin lowered the activity of pancreatic lipase, whereas the activities
2002; Ali and Blunden, 2003). Nigella sativa also contains other com- of pancreatic trypsin, chymotrypsin, and amylase were significantly
pounds such as carvone, limonene, citronellol in trace amounts, and enhanced by the same (Platel and Srinivasan, 2000a). When given as a
two varieties of alkaloids, i.e. isoquinoline alkaloids (e.g. nigellicimine single oral dose, cumin exerted a lowering effect on pancreatic lipase,
and nigellicimine-N-oxide) and pyrazole alkaloids (e.g. nigellidine amylase, trypsin, and chymotrypsin. Among the terminal digestive
and nigellicine). Nigella sativa seeds also contain α-hederin, a water enzymes, a small intestinal maltase activity was significantly higher in
soluble pentacyclic triterpene (Al-Jassir, 1992; Nickavar et al., 2003). animals fed with cumin, whereas lactase and sucrose were unaffected
The pharmacological properties of N. sativa are mainly attributable (Platel and Srinivasan, 1996).
to its quinine constituents, TQ being the most abundant. The N. sativa Dietary cumin had a significant stimulatory effect on bile flow
seeds contain fatty oil rich in unsaturated fatty acids, constituting lino- rate, the extent of increase in bile volume being 25 per cent, whereas
leic acid (50%–60%), oleic acid (20%), eicosadienoic acid (3%), and its single oral dose did not have any effect on bile secretion rate
dihomolinoleic acid (10%), and saturated fatty acids (palmitic and (Platel and Srinivasan, 2000b). Dietary intake of cumin had a pro-
stearic acids) constitute up to 30 per cent. α-Sitosterol is the major found influence on bile acid output (quantity secreted per unit time),
sterol, accounting for 44%–54% of the total sterols in N. sativa oils, bile acid secretion being as high as 70 per cent over the control.
followed by stigmasterol (6.57%–20.9% of total sterols) (Cheikh- Similar significant increases in bile acid secretion were seen in the
Rouhou et al., 2008; Mehta et al., 2008). case of cumin when administered as a single oral dose. Since bile
Bitter cumin (Shahi jeera) seeds contain calcium, vitamin A, po- juice makes a significant contribution to the overall process of diges-
tassium, sodium, iron, magnesium, and phosphorus. Bitter cumin tion and absorption, essentially by supplying bile acids required for
(B.  persicum) has 0.5 to 1.6 per cent essential oil, mainly carvone micelle formation, it is expected that cumin, which has a digestive
(45%–60%), limonene, and p-cymene. Oleoresin of bitter cumin is stimulant action, could do so by stimulating biliary secretion of
brownish to yellowish green. As there is not enough scientific infor- bile acids.
mation on the health effects of bitter cumin, this review is limited Another study has examined whether this digestive stimulant
to C.  cyminum (cumin seeds) and N.  sativa (black seeds or black spice cumin also affects the duration of residence of food in the
cumin) 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
Health effects of C. cyminum dietary cumin roughly correlates with their beneficial influence either
Although the seeds of cumin (C. cyminum L.) are widely used as the on digestive enzymes or bile secretion.
spice for their distinctive aroma, they are also commonly used in
traditional medicine to treat a variety of diseases, including chronic Antidiabetic effects
diarrhoea and dyspepsia, acute gastritis, diabetes, and cancer. The The antidiabetic effect of cumin seeds has been reported in human
literature presents ample evidence for the biological and biomedical diabetics (Karnick, 1991) (Table 2). In this study, 80 patients with
activities of cumin, which have generally been ascribed to its bio- non-insulin dependent diabetes mellitus were orally administered for
active constituents such as terpenes, phenols, and flavonoids (Mnif 24 weeks with an Ayurvedic formulation containing C.  cyminum.
and Aifa, 2015). Those health effects of cumin seeds that are experi- Fasting and post-prandial blood sugar at 6-week intervals was
mentally validated (Figure 3) are discussed below. significantly reduced in all the patients. Dietary cumin seeds were
observed to alleviate diabetes-related metabolic abnormalities in
Digestive stimulant action STZ-diabetic rats (Willatgamuwa et  al., 1998). An 8-week dietary
In the context of cumin seeds being claimed in home remedies and regimen containing cumin powder (1.25%) was found to be remark-
traditional medicine, to aid digestion, an animal study has examined 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 Nigella sativa Cuminum nigrum or Bunium persicum
Genus/family Cuminum/Apiaceae (member of Nigella/Ranunculaceae Cuminum/Apiaceae
Parsley family)
Native of countries East Meditaranian to South Asia. South to Southwest Asia. Middle Eastern Central Asia to Northern India.
growing Now mostly grown in Pakistan, India, Mediterranean region, South Europe, Mountainous regions of North India

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Uzbekistan Iran, Turkey, Morocco, Northern India, Pakistan, Syria, Turkey,
Egypt, Syria, Chile, Mexico, and China Iran, and Saudi Arabia
Traditional uses Both whole and ground seeds are used A spice in Indian and Middle Eastern A spice in Northern Indian cookery, often
in the cuisines of many cultures for cuisines. In the ancient Egypt, it was the Moghul cooking
ages. It has also many uses in trad- used as a preservative in mummification.
itional medicine. They are used in Traditionally, it is used for asthma, dia-
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 glibenclamide (Jagtap and Patil, 2010). In vitro studies indicated that
also effectively countered by dietary cumin in alloxan-diabetic rats cumin inhibited free radicals and AGE formation. The antidiabetic
(Dandapani et al., 2002). effect of cumin (treated for 4 weeks) was comparable to glibencla-
Cuminum nigrum seeds or their water or methanol extracts mide and even better in controlling oxidative stress and AGE forma-
have been observed to be hypoglycemic in alloxan-diabetic rab- tion, which is implicated in pathogenesis of diabetic microvascular
bits (Akhtar and Ali, 1985). The antihyperglycemic influence of complications. The inhibitory activity of C. cyminum seed–isolated
C. nigrum has been attributed to the flavonoid compounds present component cuminaldehyde has been evaluated against lens aldose
in these seeds (Roman-Ramos et  al., 1995; Ahmad et  al., 2000). reductase and α-glucosidase isolated from Sprague-Dawley rats and
Methanolic extract of C.  cyminum has been investigated in strep- compared with that of quercetin as an aldose reductase inhibitor and
tozotocin-diabetic rats on diabetes, oxidative stress, and forma- acarbose as an α-glucosidase inhibitor (Lee, 2005). Cuminaldehyde
tion of advanced glycated end products (AGE) in comparison with 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 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.
Patients with Cumin extract significantly decreased the level of oxLDL while increasing the Samani and Farrokhi, 2014
hypercholesterolemia activities of paraoxonase, and arylesterase activities were increased in serum

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Anti-inflammatory effect
LPS-stimulated RAW 264.7 cells Cumin essential oil exerted anti-inflammatory effects via inhibition of Wei et al., 2015
NF-κB and mitogen-activated protein kinases ERK and JNK
Chemopreventive effect
Mice 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,
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- while increasing the activities of paraoxonase, and arylesterase activi-
ful for antidiabetic therapeutics. ties were increased in serum (Samani and Farrokhi, 2014). The effect
of cumin added to normal and hypercholesterolemia inducing diet on
Anti-inflammatory effects serum and liver cholesterol levels in rats has been studied (Sambaiah
Cumin essential oil was investigated for the anti-inflammatory effects and Srinivasan, 1991). Dietary cumin did not show any cholesterol
in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the lowering effect when included in the diet (1.25%) at about 5-fold the
underlying mechanisms (Wei et al., 2015) (Table 3). Volatile constitu- normal consumption level.
ents were identified in essential oil using Gas Chromatography - Mass
Spectrometry (GC-MS), the most abundant constituent being cumi- Chemopreventive effects
naldehyde (48.8%). Cumin oil exerted anti-inflammatory effects in Cancer chemopreventive potentials of dietary 2.5 and 5.0 per cent
LPS-stimulated RAW cells through inhibiting NF-κB and mitogen- cumin were evaluated against benzo(α)pyrene-induced tumorigenesis
activated protein kinases suggesting its potential as an anti-inflam- in forestomach and 3-methylcholanthrene (MCA)-induced tumorigen-
matory agent. esis in uterine cervix in mice (Gagandeep et al., 2003) (Table 3). Cumin
produced a significant inhibition of stomach tumour. The effect on car-
Cardio-protective influence through hypolipidemic cinogen/xenobiotic metabolizing phase I and phase II enzymes, antioxi-
and hypotensive effects dant enzymes, and lipid peroxidation in the liver was also examined.
Cuminum cyminum is traditionally used for the treatment of indigestion Cytochrome P450 and cytochrome b5 were significantly augmented by
and hypertension. The anti-hypertensive potential of aqueous extract dietary cumin. The phase II enzyme glutathione-S-transferase (GST)
of cumin seed and its role in arterial–endothelial nitric oxide synthase was increased by cumin, whereas the specific activities of superoxide
expression, inflammation, and oxidative stress have been evaluated in dismutase (SOD) and catalase were significantly elevated. Lipid peroxi-
renal hypertensive rats (Kalaivani et al., 2013) (Table 3). Cumin admin- dation was inhibited by cumin, suggesting that the cancer chemopre-
istered orally (200 mg/kg body) for 9 weeks improved plasma nitric ventive potential of cumin could be attributed to its ability to modulate
oxide and reduced the systolic blood pressure in hypertensive rats. This carcinogen metabolism.
was accompanied by the up-regulation of the expression of inducible The effect of cumin (C. cyminum; dietary 1.25% for 32 weeks)
nitric oxide synthase (iNOS), Bcl-2, TRX1, and TRXR1 and down- was studied on colon cancer induced in rats by 1,2-dimethylhydrazine
regulation of the expression of Bax, TNF-α, and IL-6. These data sug- (DMH) s.c. 20 mg/kg of body weight (15 doses, at weekly intervals)
gest that cumin seeds augment endothelial functions and ameliorate (Nalini et al., 2006). Results showed that cumin suppresses colon car-
inflammatory and oxidative stress in hypertensive rats. cinogenesis in the presence of the procarcinogen DMH. The excretion
Paraoxanase-1 plays a protective role against the oxidative modi- of fecal bile acids and neutral sterols was significantly increased in
fication of plasma lipoproteins and hydrolyzes lipid peroxides in cumin+DMH-administered rats. Cholesterol and 3-hydroxy-3-meth-
human atherosclerotic lesions. Flavonoids present in cumin seeds ylglutaryl-CoA reductase activity were decreased in cumin+DMH-
are recognized to have antioxidant activity and improve the antioxi- treated rats. Spent cumin generated from Ayurvedic industry was
dant system. A study demonstrated that cumin extract significantly evaluated for its nutraceutical potential in terms of antioxidant (in
decreased the level of oxidized Low-density lipoprotein (OxLDL) 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 The oil of N. sativa significantly lowered blood glucose in STZ-diabetic El-Dakhakhny et al., 2002
rats after 2, 4, and 6 weeks
Rat pancreatic islets Defatted extract of N. sativa seed increased glucose induced insulin re- Rchid et al., 2004
lease from isolated rat pancreatic islets in vitro
STZ/NA-diabetic hamsters N. sativa oil treatment for 4 weeks decreased blood glucose and Fararh et al., 2002
increased serum insulin

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STZ-diabetic hamsters 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
Hepatocytes (HepG2) Defatted extract of N. sativa seeds increased glucose consumption by Yuan et al., 2014
hepatocytes (HepG2) in vitro through activation of AMPK
Diabetic rabbits N. sativa extract (orally for 2 months) decreased lipid peroxidation and Meral et al., 2001
increased antioxidant defense system
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 abundant natural compound, cuminaldehyde can modulate α-SN
glucose uptake activity in L6 cells), and anticancer properties (in fibrillation, suggesting that such natural active aldehyde could have
terms of arresting the cell cycle and inducing apoptosis in HT29 potential therapeutic applications (Morshedi et al., 2015).
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- Health effects of N. sativa
tion or management of degenerative diseases. Black cumin (N.  sativa) has been in use in traditional systems of
medicine for various medical disorders. Nigella sativa is used in
Miscellaneous nutraceutical effects Moroccan folk medicine for the treatment of diabetes mellitus.
Cumin seeds are traditionally used for the treatment of diarrhoea. Many pre-clinical and clinical trials have investigated its efficacy,
The aqueous extract of cumin seeds (100, 250, and 500 mg/kg) has using the seed oil, essential oil, and its isolated main constituent TQ
been examined against diarrhoea in albino rats induced with castor (Ali and Blunden, 2003). These investigations provide preliminary
oil (Sahoo et  al., 2014). The extract showed significant inhibition support for its use in asthma, allergic rhinitis, and atopic dermatitis
in the frequency of diarrhoea, delaying the defecation time, secre- (Yarnell and Abascal, 2011). Black cumin might help in dyspepsia,
tion of intestinal fluid, and intestinal propulsion in a dose-dependent respiratory problems, diabetes mellitus, and metabolic syndrome
manner. Fibrillation of α-synuclein (α-SN) is a critical process in the (Yarnell and Abascal, 2011). A  meta-analysis of clinical trials sug-
pathophysiology of several neurodegenerative diseases, especially gests that N. sativa has a short-term benefit in lowering systolic and
Parkinson’s disease. A study on the inhibitory effects of C. cyminum diastolic blood pressure, and its various extracts can reduce triglyc-
essential oil on the fibrillation of α-SN indicated that the small 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 N. sativa extract ameliorated benz(a-)pyrene-induced carcinogenesis in Aruna and Sivarama-krishnan,
the forestomach 1990
Rat—DMH-induced colon cancer 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
Rats—gastric ulcer induced by necrotiz- N. sativa aqueous suspension significantly ameliorated the ulcer severity Al Mofleh et al., 2008

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ing agents and basal gastric acid secretion. The anti-ulcer effect is possibly prosta-
glandin-
mediated and/or through its antioxidant and anti-secretory activities
Wistar rats—colon cancer induced with 1000 or 4000 ppm N. sativa volatile oil in the diet for 30 weeks signifi- Salim, 2010
carcinogens cantly reduced malignant and benign colon tumour sizes, incidences and
multiplicities
Rats—colitis induced with TNBS Oral N. sativa oil, by preventing inflammatory status in the blood, partly Isik et al., 2011
protected colonic tissue against experimental ulcerative colitis
Rat—DMBA-induced breast cancer 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
Children with acute lymphoblastic Black cumin seeds (80 mg/kg/day for 1 week) decreased methotrexane Hagag et al., 2015
leukaemia hepatotoxicity and improved survival in children with leukaemia
Cancer cells Thymoquinone suppressed tumour cell proliferation in colorectal Gali-Muhtasib et al., 2006
carcinoma, breast adenocarcinoma, osteosarcoma, ovarian carcinoma,
myeloblastic leukaemia, and pancreatic carcinoma
Cancer cells 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
Prostate cancer (PC-3) cell TQ is shown to prevent tumour angiogenesis in a xenograft human Yi et al., 2008
cancer model
MCF-7 cells 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
Human cervical squamous carcinoma TQ was with IC50 values of 10.7 µg/ml; elimination of SiHa cells via Ng et al., 2011
cells (SiHa) apoptosis with down-regulation of the Bcl-2 protein
Human osteosarcoma cell line SaOS-2 Anti-tumour and anti-angiogenic activity of TQ possibly mediated by an Peng et al., 2013
inhibition of NF-κB and downstream effector molecules
Breast cancer MDA-MB-231 cells 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
Pancreatic cancer cells 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
Panc-1 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
PC-3 cells Administration of N. sativa reduced the carcinogenic effects of DMBA in Shafi et al., 2008
mammary carcinoma
Gastric cancer cells 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- vitro in rat pancreatic islets in the presence of glucose (8.3 mmol/l).
cial effects particularly in diabetes, dyslipidemia, hypertension, and Results showed that the antidiabetic properties of N.  sativa seeds
obesity. A  systematic review of all human trials has revealed that may partially be mediated by the stimulation of insulin release, espe-
N. sativa supplementation might be effective in glycemic control in cially by the basic subfraction of the seed. The possible insulinotropic
humans (Mohtashami and Entezari, 2016). 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
Antidiabetic effects serum insulin (Fararh et  al., 2002). Immunohistochemical staining
Nigella sativa seeds are traditionally used in the management of dia- revealed the presence of insulin in the pancreas from N. sativa oil-
betes mellitus in indigenous systems of medicine and folk remedies. treated group, suggesting that the hypoglycemic effect results, at
Defatted extract of N.  sativa seed is reported to increase glucose- least partly, from a stimulatory effect on β-cell function.
induced insulin release from isolated rat pancreatic islets in vitro The oil of N. sativa significantly lowered blood glucose in STZ-
(Rchid et al., 2004) (Table 4). The effect of N. sativa extracts (defatted diabetic rats after 2, 4, and 6 weeks (El-Dakhakhny et  al., 2002).
fractions either containing acidic and neutral compounds or contain- A study of the effect of N. sativa oil on insulin secretion from iso-
ing basic compounds) have been investigated on insulin secretion in 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

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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-
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 Nigella sativa oil administration (daily) to STZ-induced diabetic
rather than by stimulation of insulin release. The hypoglycemic rats maintained on a high-fat diet significantly induced the gene
effect of N. sativa oil (400 mg/kg by p.o.) is partly due to decreased expression of insulin receptor (Balbaa et  al., 2016). Nigella sativa
hepatic gluconeogenesis (Fararh et al., 2004). Indazole-type alkaloid oil upregulated the expression of IGF-1 and phosphoinositide-3 kin-
17-O-(β-D-glucopyranosyl)-4-O-methyl nigellidine present in the ase, whereas the expression of ADAM-17 was downregulated. Also,
defatted extract of N.  sativa seeds increased glucose consumption the N.  sativa oil significantly reduced blood glucose level, individ-
by hepatocytes (HepG2 cells) in vitro through activation of AMP- ual lipid profile, oxidative stress markers, serum insulin or insulin
activated protein kinase (AMPK) (Yuan et al., 2014). receptor ratio, and the TNF-α, confirming that N. sativa oil has an
Nigella sativa extract given orally for 2 months decreased lipid antidiabetic activity. Thus, the daily N. sativa oil treatment improves
peroxidation and increased antioxidant defence system and also insulin-induced signalling.
prevented the lipid peroxidation-induced liver damage in diabetic Hyperglycaemia is an important risk factor for the development
rabbits (Meral et al., 2001). Daily oral administration of ethanol and progression of the macrovascular and microvascular complica-
extract of N.  sativa seeds (300  mg/kg) to STZ-diabetic rats for tions that occur in diabetes. The expression of apoptotic markers in
30 days reduced the elevated levels of blood glucose, lipids, plasma the medial aortic layer of diabetic rats and the effects of N. sativa
insulin, and improved altered levels of lipid peroxidation products seed oil on the expression of these markers have been investigated
and antioxidant enzymes in liver and kidney (Kaleem et al., 2006). (Cüce et al., 2015). It is understood that N. sativa seed oil is effective
This suggested that in addition to antidiabetic activity, N.  sativa against diabetes and merits further treatment strategies for prevent-
seeds may control diabetic complications through antioxidant ing apoptosis in vascular structures.
effects. Treatment of N.  sativa oil (0.2  ml/kg, i.p.) for 30  days Treatment of streptozotocin-diabetic rats with N. sativa extract,
decreased the elevation in serum glucose and restored lowered N. sativa oil, and TQ, significantly decreased the diabetes-induced
serum insulin with partial regeneration or proliferation of pancre- lipid peroxides and hyperglycemia, and significantly increased
atic β-cells in STZ-diabetic rats (Kanter et al., 2003). The possible serum insulin and SOD activity in tissues. Nigella sativa oil and
protective effects of N. sativa (0.2 ml/kg, i.p.) against β-cell damage TQ have therapeutic potential and are protective against STZ-
from STZ-diabetes in rats have been evidenced by the observed diabetes by decreasing oxidative stress, thus preserving pancreatic
decrease in lipid peroxidation and serum nitric oxide and increase β-cell integrity, leading to increased insulin levels (Abdelmeguid
in the activities of antioxidant enzymes in the pancreas (Kanter et al., 2010). The protective effects of N. sativa oil on insulin sen-
et  al., 2004). Increased staining for insulin and preservation of sitivity and ultrastructural changes of pancreatic β-cells in STZ-
β-cell numbers were evident in N.  sativa–treated diabetic rats. induced diabetic rats are reported (Kanter et al., 2009). It is evident
This suggests that N. sativa treatment exerts a protective effect on that N.  sativa treatment exerts a protective effect on diabetes by
diabetes by decreasing oxidative stress and preserving pancreatic decreasing morphological changes and preserving the pancre-
β-cell integrity. 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

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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
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 useful adjuvant to oral hypoglycemic drugs in patients with type
carbohydrate metabolism in STZ-NA–induced diabetic rats have 2 diabetes mellitus.
been evaluated (Pari and Sankaranarayanan, 2009). Oral admin-
istration of TQ (20, 40, and 80  mg/kg body weight for 45  days) Ameliorative effects of N. sativa on dyslipidemia
dose-dependently improved the glycemic status in STZ/NA-induced Dyslipidemia is an established risk factor for ischemic heart disease.
diabetic rats. The levels of insulin and haemoglobin increased along Nigella sativa has been used for the treatment and prevention of hyper-
with a decrease in glucose and HbA1c levels. The altered activities lipidemia (Asgary et  al., 2015). Different preparations of N.  sativa
of carbohydrate-metabolizing enzymes were also restored (Pari and including seed powder (100 mg–20  g daily), seed oil (20–800  mg
Sankaranarayanan, 2009). daily), TQ (3.5–20 mg daily), and methanolic extract reduced plasma
In a clinical study, the adjuvant effect of N. sativa oil on vari- levels of total cholesterol, low-density lipoprotein cholesterol, and tri-
ous clinical and biochemical parameters of the insulin resistance glycerides. In clinical trials, N. sativa was found to be effective when
syndrome in patients with diabetes and dyslipidemia has been evi- added as an adjunct to conventional hypolipidemic and antidiabetic
denced (Najmi et  al., 2008). Nigella sativa accentuates glucose- medications. Inhibition of dietary cholesterol absorption, decreased
induced secretion of insulin besides negatively affecting glucose hepatic cholesterol synthesis, and up-regulation of LDL receptors
absorption. Hence, it is of immense therapeutic benefit in diabetic contribute to lipid-lowering effects of N. sativa. Overall, the evidence
individuals (Kapoor, 2009). The effect of N. sativa seeds used as from an experimental and a clinical study suggests that N. sativa seeds
an adjuvant therapy in addition to the anti-diabetic medications are promising natural therapy for patients with dyslipidemia.
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- Anti-inflammatory property and analgesic activity
cose, 2-hour post-prandially, and glycosylated haemoglobin. The The antinociceptive and anti-inflammatory effects of TQ (Table 6),
results indicate that a dose of 2 g/day of N. sativa could serve as a supporting the common perception of N. Sativa as a potent analgesic
10 K. Srinivasan, 2018, Vol. 2, No. 1

and anti-inflammatory agent, have been recently reviewed (Amin regulation of immune reactions in infectious and non-infectious con-
and Hosseinzadeh, 2016). Many protective properties are attributed ditions such as allergy, autoimmunity, and cancer.
to radical scavenging activity as well as an interaction with molecu- The potential immunomodulatory effects of aqueous extract of
lar targets involved in inflammation (proinflammatory enzymes and N.  sativa investigated in BALB/c mice and C57/BL6 primary cells
cytokines). Further investigations are needed to understand the pre- with respect to splenocyte proliferation, macrophage function, and
cise mechanisms responsible for the antinociceptive and anti-inflam- anti-tumor activity demonstrated that N. sativa significantly enhances
matory effects of its active constituents. splenocyte proliferation in a dose-responsive manner (Ghonime
Development of solid tumour malignancies is closely associated et al., 2011). Aqueous extract of N. sativa significantly suppressed
with inflammation. The steam-distilled essential oil of N.  sativa, the secretion of key proinflammatory mediators (IL-6, TNF-α, and

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which mainly contains p-cymene (37.3%) and TQ (13.7%), investi- NO) by primary macrophages indicating anti-inflammatory effects
gated for its analgesic and antiinflammatory properties in rats was in vitro. Nigella sativa methanolic extract treatment (intraperito-
found to produce a significant analgesic effect on acetic acid-induced neal) enhanced the total white blood cells count and increased spleen
writhing, formalin, and light tail flick tests (Hajhashemi et  al., weight in BALB/c mice, suggesting the immunomodulatory activity
2004). Intraperitoneal injection of 100, 200, and 400 µl/kg signifi- of N. sativa seeds (Ghonime et al., 2011). Treatment with N. sativa
cantly inhibited carrageenan-induced paw oedema. Mechanism(s) oil significantly decreased the antibody production in response to ty-
other than opioid receptors are believed to be involved in this an- phoid vaccination (antigen typhoid TH) in a Long-Evans rat model.
algesic effect of the Nigella essential oil. Its administration showed These results indicated that the N. sativa seeds could be considered
anti-inflammatory activity probably attributable to TQ, one of the as a potential immunosuppressive cytotoxic agent (Torres et  al.,
major components of black cumin. The anti-inflammatory effect 2010). Co-administration of N. sativa (2.5%) with oxytetracycline
of TQ on LPS-stimulated BV-2 murine microglia cells has been completely blocked the leukocyte and lymphocyte decreasing effects
reported, wherein TQ was effective in reducing nitrate with parallel elicited by oxytetracycline and produced immunostimulant effects
decline of iNOS protein expression evidenced (Taka et al., 2015). TQ in pigeons indicating an immune-protective effect (Abel-Salam,
also reduced LPS-mediated elevation in gene expression of Cxcl10 2012). Nigella sativa oil is also shown to have a promising radio-
and some of other cytokines. The anti-inflammatory properties of protective action against immunosuppressive and oxidative effects
TQ in LPS-activated microglial cells suggested the applicability of of γ-radiation in rats (Assayed, 2010). Nigella sativa seed extract
TQ in delaying the onset of inflammation-mediated neurodegenera- significantly improved symptoms and immune parameters in murine
tive disorders. ovalbumin-induced allergic diarrhoea in mice (Duncker et al., 2012).
The aqueous extract of N.  sativa has been found to pos-
sess anti-inflammatory and analgesic activities in animal models. Antioxidant and antimicrobial activity
Although osteoporosis is linked to oxidative stress and inflamma- An evaluation of the essential oil of N.  sativa seeds, for antioxi-
tion, the anti-osteoporotic effects of N. sativa and TQ are evidenced dants, showed that TQ and other components (carvacrol, t-anet-
by observing the inhibition of inflammatory cytokines (interleukin hole, and 4-terpineol) have a radical scavenging property. These
(IL)-1 and 6)  and the transcription factor (NFκB). Both N.  sativa constituents and the essential oil showed variable antioxidant ac-
and TQ have shown potential as an anti-osteoporotic agent (Shuid tivity when tested in the diphenylpicrylhydrazyl assay; they also ef-
et  al., 2012). TQ induced apoptosis and inhibited proliferation in fectively scavenged OH radical in the assay for non-enzymatic lipid
pancreatic ductal adenocarcinoma (PDA) cells. This anti-inflam- peroxidation.
matory potential involved an effect on the expression of different TQ has been shown to suppress the ferric nitrilotriacetate-
proinflammatory cytokines and chemokines. TQ dose-dependently induced oxidative stress in Wistar rats (Khan and Sultana, 2005).
reduced PDA cell synthesis of MCP-1, TNF-α, IL-1β, and Cox-2. Dietary N. sativa seeds inhibited the oxidative stress caused by oxi-
TQ as an inhibitor of proinflammatory pathways provides an ef- dized corn oil in rats (Al-Othman et  al., 2006). Dietary N.  sativa
fective strategy that combines anti-inflammatory and proapoptotic (10%) neutralized the oxidative stress induced by hepatocarcinogens
modes of action (Chehl et al., 2009). A clinical trial was conducted such as dibutylamine and sodium nitrate in albino rats by normal-
to investigate the anti-inflammatory effects of N. sativa in patients izing glutathione and nitric oxide levels (Gendy et  al., 2007). The
with allergic rhinitis symptoms. The anti-allergic effects of N. sativa N. sativa seed oil and TQ (intraperitoneal) are shown to have pro-
components could be attributed to allergic rhinitis (Nikakhlagh tective effects on lipid peroxidation process during ischemia-reperfu-
et  al., 2011). The anti-arthritic activity of orally administered TQ sion injury in rat hippocampus (Hosseinzadeh et al., 2007). Treating
(5 mg/kg body once daily for 21 days) in collagen-induced arthritic broiler chicks with N.  sativa seed for 6 weeks reduced the oxida-
Wistar rats was evidenced with significantly reduced proinflamma- tive stress in the liver by increasing the activities of myeloperoxi-
tory mediators [IL-1β, IL-6, TNF-α, IFN-γ, and PGE2] and increased dase, glutathione-S-transferase, CAT, adenosine deaminase, and by
IL-10 (Umar et al., 2012). decreasing hepatic lipid peroxidation (Sogut et al., 2008). The TQ
pre-treatment countered the increased level of lipid peroxidation and
Immunomodulatory action augmented the antioxidant enzyme activities in the erythrocyte dur-
The immunomodulatory properties of N. sativa and its major active ing 1,2-dimethylhydrazine-induced colon carcinogenesis in Wistar
ingredient, TQ in terms of their experimentally documented abil- rats (Harzallah et al., 2012).
ity to modulate cellular and humoral adaptive immune responses The bioactive compounds of N.  sativa essential oil identified
(Table  6) have comprehensively been reviewed (Majdalawieh and using GC and GC-MS included p-cymene, TQ, α-thujene, longi-
Fayyad, 2015). The molecular and cellular mechanisms underlying folene, β-pinene, α-pinene, and carvacrol. Nigella sativa essential
such immunomodulatory effects of N. sativa and TQ are highlighted, oil exhibited different biological activities including antifungal,
and the signal transduction pathways implicated in the immunoreg- antibacterial, and antioxidant potentials. Nigella sativa essential oil
ulatory functions are suggested. Experimental evidence suggests that completely inhibited different Gram-negative and Gram-positive
N.  sativa extracts and TQ can therapeutically be employed in the bacteria (Morsi, 2000). Nigella sativa oil also exhibited stronger
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1  11

radical scavenging activity against DPPḢ radical in comparison with has been explained by its ability to modulate cell division in can-
synthetic antioxidants. cer cells, involving downregulation of Bcl-xL, cyclin D1, and VEGF
(Aggarwal et al., 2008). TQ is reported to be effective in inhibiting
Anti-cancer properties human umbilical vein EC migration and invasion, suggesting its role
The anti-cancer effect of N.  sativa has extensively been studied in in angiogenesis (Gali-Muhtasib et al., 2006). TQ is shown to prevent
different in vitro and in vivo models (Table 5). Nigella sativa is able tumour angiogenesis in a xenograft human prostate cancer (PC-3)
to exert antioxidant, anti-mutagenic, cytotoxic, pro-apoptotic, anti- model (Yi et  al., 2008). Nigella sativa, its oil, and TQ are effect-
proliferative, and anti-metastatic effects in various primary cancer ive against cancer in the blood system, lung, kidney, liver, prostate,
cells and cancer cell lines (Majdalawieh and Fayyad, 2016). The avail- breast, cervix, and skin. Some studies attribute the anti-cancer effect

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able studies strongly suggest that N. sativa could serve as an effective of TQ to its role as an antioxidant, ability to improve body’s immune
agent to control tumour initiation, growth, and metastasis independ- system, and ability to induce apoptosis and control Akt pathway
ently or in combination with conventional chemotherapeutic drugs. (Khan et al., 2011).
Nigella sativa extract ameliorated the benz(α-)pyrene- The cytotoxic effects of N.  sativa seed extract as an adjuvant
induced carcinogenesis in the forestomach in mice (Aruna and therapy to doxorubicin on human MCF-7 breast cancer cells are
Sivaramakrishnan, 1990). This is partly attributed to the ability to reported. Nigella sativa lipid extract was found to be cytotoxic to
influence phase II enzymes. Orally administered N.  sativa oil (14 MCF-7 cells with LC50 of 2.7  mg/ml, whereas its aqueous extract
weeks) interfered with the induction of aberrant crypt foci (ACF) exhibited cytotoxicity at about 50 mg/ml (Mahmoud and Torchilin,
by 1,2-dimethylhydrazine, putative preneoplastic lesions for colon 2012). TQ was found to be cytotoxic to human cervical squamous
cancer in rats (Salim and Fukushima, 2003). This inhibition may be carcinoma cells (SiHa) with IC50 values of 10.7 µg/ml as determined
associated, in part, with the suppression of cell proliferation in the by MTT assay, whereas it was less cytotoxic towards the normal cells.
colonic mucosa. Nigella sativa aqueous suspension significantly pre- Cell cycle analysis indicated induction of apoptosis by the compound
vented gastric ulcer formation experimentally induced by necrotiz- and elimination of SiHa cells via apoptosis with down-regulation
ing agents and also significantly ameliorated the severity of ulcer of the Bcl-2 protein (Ng et al., 2011). An investigation of the anti-
and gastric acid secretion in pylorus-ligated Shay rats (Al Mofleh tumour and anti-angiogenic effects of TQ on osteosarcoma in vitro
et al., 2008). and in vivo showed that TQ induced higher growth inhibition and
The chemopreventive potential of N.  sativa oil on tumour for- apoptosis in the human osteosarcoma cell line SaOS-2. TQ signifi-
mation has been revealed in a study using a rat multiorgan carcino- cantly blocked human umbilical vein endothelial cell tube formation
genesis model induced by five different carcinogens (Salim, 2010). in a dose-dependent manner. The anti-tumour and anti-angiogenic
Post-initiation administration of 1000 or 4000 ppm N. sativa vola- activity of TQ in osteosarcoma is possibly mediated by inhibition of
tile oil in the diet for 30 weeks significantly reduced colon tumour NF-κB and downstream effector molecules (Peng et al., 2013).
sizes, incidences, and multiplicities. Nigella sativa volatile oil also TQ exerted a strong anti-proliferative effect in breast cancer cells
significantly decreased the incidences and multiplicities of tumours via its potential effect on the PPAR-γ activation pathway, and in
in the lungs and alimentary canal (particularly the oesophagus and combination with doxorubicin and 5-fluorouracil, TQ’s cytotoxicity
forestomach). Thus, N. sativa exerts potential inhibitory effects on was found to be increased. Migration and invasion of MDA-MB-231
tumour development in multiple organ sites (Salim, 2010). Nigella cells were also reduced by TQ, which was found to increase PPAR-γ
sativa oil (orally administered for 3 days) decreased the proinflam- activity and down-regulate the expression of Bcl-2, Bcl-xL, and sur-
matory cytokines (TNF-α, IL-1β, and IL-6) in the blood of rats with vivin in breast cancer cells (Woo et  al., 2011). An investigation of
experimental colitis induced with trinitrobenzene sulfonic acid (Isik the effect of TQ on pancreatic cancer cells and on MUC4 expres-
et  al., 2011). Nigella sativa oil, by preventing inflammatory status sion revealed down-regulated MUC4 expression and induced apop-
in the blood, partly protected colonic tissue against experimental tosis in pancreatic cancer cells. The decrease in MUC4 expression
ulcerative colitis. Oral TQ (1–10  mg/kg) or N.  sativa oil (thrice was accompanied by increased apoptosis, decreased motility, and
in a week for 4  months) exerted a protective effect against breast decreased migration of pancreatic cancer cells (Torres et al., 2010).
cancer in female rats induced by 7,12-dimethylbenz[α-]anthracene The administration of N. sativa reduced the carcinogenic effects
as revealed by tumour markers, histopathological alterations, and of DMBA in mammary carcinoma which indicated its protective
the regulation of several genes (Brca1, Brca2, Id-1, and P53 muta- role in mammary carcinoma (Shafi et al., 2008). TQ dose-depend-
tion) related to breast cancer (Linjawi et al., 2015). ently suppressed the migration and invasion of Panc-1 cells. TQ
Acute lymphoblastic leukaemia (ALL) is a common childhood also significantly down-regulated NF-kB and MMP-9 in Panc-1
malignancy and is conventionally treated with methotrexate which cells. Administration of TQ significantly reduced tumour metasta-
also produces hepatotoxicity. The therapeutic value of N. sativa oil sis. Furthermore, the expression of NF-kB and MMP-9 protein in
in methotrexate-induced hepatotoxicity has been assessed in 40 tumour tissues was down-regulated after treatment with TQ, thus
Egyptian children with ALL under methotrexate therapy (Hagag exerting anti-metastatic activity on pancreatic cancer both in vitro
et al., 2015). Nigella sativa oil (80 mg/kg/day for 1 week) produced and in vivo (Wu et al., 2011). The chemo-sensitizing effect of TQ and
significant differences in remission, relapse, death, and disease-free 5-fluorouracil (5-FU) on gastric cancer cells both in vitro and in vivo
survival. Nigella sativa seeds decreased methotrexate hepatotoxicity is reported (Lei et  al., 2012). Pre-treatment with TQ significantly
and improved survival. This report is suggestive of its application as increased the apoptotic effects induced by 5-FU in gastric cancer cell
an adjuvant drug in patients under methotrexate therapy. lines in vitro. The combined treatment of TQ with 5-FU was more
Nigella sativa seed oil and TQ have been understood to exert effective in anti-tumour action than either of them individually in a
antioxidant and chemopreventive properties (Allahghadri et  al., xeno-graft tumour mouse model. The TQ/5-FU-combined treatment
2010). TQ could suppress tumour cell proliferation in the case of induces apoptosis by enhancing the activation of both caspase-3 and
breast adenocarcinoma, pancreatic carcinoma, colorectal carcin- caspase-9 in gastric cancer cells (Lei et al., 2012).
oma, osteosarcoma, ovarian carcinoma, and myeloblastic leukaemia In summary, N. sativa oil and TQ are found to inhibit experimen-
(Allahghadri et al., 2010). The cancer chemopreventive ability of TQ tal carcinogenesis in different animal models. It has been shown to
12 K. Srinivasan, 2018, Vol. 2, No. 1

arrest the growth of various cancer cells in culture as well as xeno- and reduced the occurrence of diarrhoea and body weight loss,
graft tumours in vivo. The mode of anticancer effects of TQ includes associated with amelioration of colitis-related damage. Also, there
inhibition of carcinogen-metabolizing enzyme activity and oxidative was a significant reduction in colonic myeloperoxidase activity and
damage to cellular macromolecules, amelioration of inflammation, malondialdehyde levels and an increase in glutathione levels (Lei
inhibition of cell cycle and apoptosis in tumour cells, inhibition of et al., 2012).
tumour angiogenesis, and suppression of migration, invasion, and
metastasis of cancer cells. TQ improves anti-cancer effects when Nephroprotective effect
combined with conventionally used chemotherapeutic agents. At the The nephroprotective effect of N.  sativa oil is observed in gen-
molecular level, TQ targets intracellular signalling pathways, par- tamicin-induced nephrotoxicity in rabbits (Saleem et  al., 2012)

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ticularly a variety of kinases and transcription factors, which are (Table 7). Vitamin C and N.  sativa oil when given as combination
activated during tumourigenesis. 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
Gastroprotective effect 10  days) produced a dose-dependent amelioration of gentamycin-
Nigella sativa oil and its constituents are proved to exert gastro- induced nephrotoxicity in rats as assessed by the biochemical and
protective effect (Table 7); some of the potential mechanisms exhib- histological indices of nephrotoxicity (Ali, 2004). The protective
ited by N. sativa in preventing or curing gastric ulcers are reviewed effect of N. sativa oil on methotrexate-induced nephrotoxicity has
recently (Khan et  al., 2016). The mechanism of gastroprotective been reported in albino rats which is medicated through restoring
effect of TQ has been assessed in rats injected with TQ (10 and the antioxidant status (Abul-Nasr et al., 2001; Yaman and Balikci,
20  mg/kg) and subsequently subjected to ischemia or reperfusion 2010). The protective effects of N.  sativa oil in the prevention of
insult. TQ restored the altered acid secretion, gastric mucosal con- chronic cyclosporine A-induced nephrotoxicity in rats were evi-
tent, lipid peroxide, and the activity of myeloperoxidase, reduced denced by attenuation of the oxidative stress (Uz et al., 2008). TQ
glutathione, and total nitric oxide along with ulcer index, the effi- supplementation prevented the development of gentamycin-induced
cacy being comparable with that of the reference drug omeprazole. degenerative changes in kidney tissues and cisplatin-induced renal
TQ exerted gastroprotection via inhibiting proton pump, acid secre- injury in rats as indicated by lipid peroxides and renal organic anion
tion and neutrophil infiltration, while enhancing mucin secretion, and cation transporters (Sayed-Ahmed and Nagi, 2007; Ulu et al.,
and nitric oxide production, in addition to the antioxidant influences 2012). Nigella sativa significantly prevented renal ischemia- or rep-
(Magdy et al., 2012). erfusion-induced functional and histological injuries in Wistar rats
The anti-ulcer potential of N. sativa aqueous suspension on gas- (Mousavi, 2015). Nigella sativa showed protective effects against
tric ulcers experimentally induced with various noxious chemicals ischemia-perfusion damage on kidney tissue based on the total anti-
(indomethacin, 80% ethanol, and 0.2 M NaOH) in Wistar rats oxidant capacity, oxidative status index, and activities of catalase
was examined (Al Mofleh et al., 2008). Nigella sativa significantly and myeloperoxidase in the kidney tissue (Yildiz et al., 2010).
prevented gastric ulcer formation induced by necrotizing agents by
significantly replenishing the depleted gastric wall mucus content Hepatoprotective effect
and gastric mucosal non-protein sulfhydryl concentration. The anti- It is reported that N.  sativa (i.p.  0.2  ml/kg) relieves the deleterious
ulcer effect of N.  sativa was exerted through its antioxidant and effects of ischemia-reperfusion injury on liver in rats, as indicated by
anti-secretory activities (Al Mofleh et al., 2008). Both N. sativa (2.5 titers of marker enzymes, total antioxidant capacity, total oxidative
and 5.0 ml/kg, p.o.) and TQ (5, 20, 50, and 100 mg/kg, p.o.) were status, and myeloperoxidase in the liver tissue (Yildiz et  al., 2008)
found to possess gastro-protective activity against gastric mucosal (Table 7). The protective effect of TQ on the Cd++-induced hepato-
injury induced by ischemia or reperfusion in Wistar rats (El-Abhar toxicity in mice, particularly the perturbation of non-enzymatic and
et al., 2003). Lipid peroxidation and lactate dehydrogenase, elevated enzymatic antioxidants, has been reported (Zafeer et al., 2012). Pre-
by the ischemia or reperfusion insult and decreased glutathione and treatment with TQ (10  µmol/l) showed a significant protection as
activity of SOD accompanied by an increased formation of gastric indicated by an attenuation of protein oxidation and recovery of the
lesions, were countered by N.  sativa or TQ treatment, indicating depleted antioxidants, suggesting that TQ exerts modulatory influence
their gastroprotective effect, probably by conservation of the gastric on the antioxidant defence system when subjected to toxic insult.
mucosal redox state.
Nigella sativa and TQ are reported to protect gastric mucosa Pulmonary-protective activity and anti-asthmatic
against the ulcerating effect of alcohol on hypothyroidal rats and effects
mitigate most of the biochemical adverse effects on gastric mucosa, Nigella sativa has been investigated for the possible beneficial
viz., increase in lipid peroxidation and reduced gastric glutathione effects on experimental lung injury in rats after pulmonary aspir-
content, and enzyme activities of gastric SOD and GST (Khaled, ation (Kanter, 2009) (Table 7) and found that N.  sativa treatment
2009). The beneficial effect of N.  sativa oil (2  ml/kg daily, i.p.) inhibits the inflammatory pulmonary responses. Nigella sativa ther-
in rats with necrotizing enterocolitis (NEC) was studied in new- apy resulted in a significant reduction in the activity of iNOS and
born Sprague-Dawley rats (Tayman et al., 2012). Histopathologic an increase in surfactant protein D in the lung tissue of different
and apoptosis evaluation indicated that the bowel damage was less pulmonary aspiration models. It is concluded that N.  sativa treat-
severe in the N. sativa oil–treated group. Nigella sativa oil had a ment might be beneficial in lung injury that merits potential clinical
beneficial preserving effect on tissue antioxidant enzymes, whereas use. The ameliorative effect of N. sativa oil in rats with hyperoxia-
lipid peroxide levels were significantly lower than those in the NEC induced lung injury has also been reported (Tayman et al., 2012).
control group. In a mouse model of inflammatory bowel disease The prophylactic effect of an extract of N.  sativa (15  ml/kg of
(C57BL/6 murine colitis induced with dextran sodium sulfate), 0.1 g% boiled extract for 3 months) has been examined in asthmatic
treatment with TQ (5, 10, or 25 mg/kg) ameliorated colonic inflam- adults. All asthma symptoms, the frequency of symptoms, chest wheez-
mation (Lei et al., 2012). The treatment of mice with TQ prevented ing, and pulmonary function tests (PFT values) were significantly
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1  13

improved as a result of N.  sativa treatment, generally suggesting a constituents like TQ could be used in suitable combinations with
prophylactic effect on asthma disease (Boskabady et  al., 2007). TQ conventional therapeutic agents for maximizing the effectiveness in
potently and dose-dependently inhibited the formation of leukot- the treatment of many infectious diseases and also to circumvent the
rienes—supposedly important mediators in asthma and inflammatory drug resistance problem. Further investigations are recommended to
processes, in human blood cells (Mansour and Tornhamre, 2004). explore the specific cellular and molecular targets of various con-
stituents of N. sativa, particularly TQ.
Miscellaneous nutraceutical effects
During the last three decades, several in vitro and in vivo animal References
studies have ascertained the pharmacological properties of N. sativa,

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Abdelmeguid, N. E., Fakhoury, R., Kamal, S. M., Al Wafai, R. J. (2010).
including its antioxidant, antibacterial, anti-proliferative, proa- Effects of Nigella sativa and thymoquinone on biochemical and subcel-
poptotic, anti-inflammatory, and antiepileptic properties, and its lular changes in pancreatic β-cells of streptozotocin-induced diabetic rats.
beneficial effect in conditions of atherogenesis, endothelial dys- Journal of Diabetes, 2: 256–266.
function, glucose dyshomeostasis, and disrupted lipid metabolism. Abel-Salam, B. K. (2012). Immunomodulatory effects of black seeds
Nigella sativa and its constituents are found to have antioxidant, and garlic on alloxan-induced diabetes in albino rat. Allergologia Et
antidiabetic, anti-inflammatory, and anti-tumour properties as well Immunopathologia, 40: 336–340.
Abul-Nasr, S. M., El-Shafey, M. D. M., Osfor, M. M. H. (2001). Amelioration
as therapeutic effects on metabolic syndrome, and gastrointestinal,
by Nigella sativa of methotrexate induced toxicity in male albino rats: a
neuronal, cardiovascular, and respiratory disorders in clinical trials
biochemical, haematological and histological study. Scintia Agriculturae
(Gholamnezhad et al., 2016). Experimental and clinical studies have
Bohemica, 32: 123–160.
evidenced therapeutic effects of N. sativa seed extracts, oil, and TQ Aggarwal, B. B., Kunnumakkara, A. B., Harikumar, K. B., Tharakan, S. T.,
on different disorders. Standard clinical trials are however needed for Sung, B., Anand, P. (2008). Potential of spice-derived phytochemicals for
N. sativa supplementation for its promotion as an adjuvant therapy. cancer prevention. Planta Medica, 74: 1560–1569.
Long-term administration of N. sativa increased brain serotonin Ahmad, M., Akhtar, M. S., Malik, T., Gilani, A. H. (2000). Hypoglycaemic
levels and improved learning ability and memory in rats (Perveen action of the flavonoid fraction of Cuminum nigrum seeds. Phytotherapy
et al., 2008). Chronic administration of N. sativa decreased sero- Research: PTR, 14: 103–106.
tonin turnover and produced anxiolytic effects in rats. Tryptophan Akhtar, M. S., Ali, M. R. (1985). Study of hypogiycaemic activity of Cuminum
nigrum seeds in normal and alloxan diabetic rabbits. Planta Medica, 2:
concentration in brain and plasma also increased significantly fol-
81–85.
lowing repeated oral administration of N. sativa oil, suggesting that
Akhtar, M., Maikiyo, A. M., Khanam, R., Mujeeb, M., Aqil, M., Najmi, A. K.
this oil is useful for the treatment of anxiety (Perveen et al., 2009).
(2012). Ameliorating effects of two extracts of Nigella sativa in middle
Anti-anxiety-like effects of TQ (20 mg/kg) was observed in mice, cerebral artery occluded rat. Journal of Pharmacy & Bioallied Sciences,
which involved modulation of GABA and NO levels. The anxiolytic 4: 70–75.
effect was accompanied by a significant decrease in plasma nitrite Al Mofleh, I. A., et al. (2008). Gastroprotective effect of an aqueous suspen-
and countering of decreased γ-aminobutyric acid content in the sion of black cumin Nigella sativa on necrotizing agents-induced gas-
brain (Gilhotra and Dhingra, 2011). The neuroprotective effects of tric injury in experimental animals. Saudi Journal of Gastroenterology:
the aqueous extract of N. sativa have been recorded during cere- Official Journal of the Saudi Gastroenterology Association, 14: 128–134.
bral ischemia in rats; this could be resulting from its free radical Ali, B. H. (2004). The effect of Nigella sativa oil on gentamicin nephrotoxicity
in rats. The American Journal of Chinese Medicine, 32: 49–55.
scavenging, antioxidant (elevation in reduced glutathione, SOD, and
Ali, B. H., Blunden, G. (2003). Pharmacological and toxicological properties
catalase (CAT) activities), and anti-inflammatory properties (Akhtar
of Nigella sativa. Phytotherapy Research: PTR, 17: 299–305.
et al., 2012).
Al-Jassir, M. S. (1992). Chemical composition and microflora of black cumin
The incidence of kidney stone may increase the vulnerability of (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chemistry, 45:
patients to renal failure. Nigella sativa and its main bioactive com- 239–242.
ponent—TQ showed positive effects on the prevention or dissol- Allahghadri, T., et  al. (2010). Antimicrobial property, antioxidant capacity,
ution of kidney stones and renal failure. This involves antioxidative, and cytotoxicity of essential oil from cumin produced in Iran. Journal of
anti-inflammatory, and immunomodulatory effects. Thus, N. sativa Food Science, 75: H54–H61.
and its components are beneficial in the prevention and curing of Al-Othman, A. M., Ahmad, F., Al-Orf, S., Al-Murshed, K. S., Ariff, Z. (2006).
nephrolithiasis and renal damages (Hayatdavoudi et al., 2016). Effect of dietry supplementation of Ellataria cardamun and Nigella
sativa on the toxicity of rancid corn oil in rats. International Journal of
Pharmacology, 2: 60–65.
Amin, B., Hosseinzadeh, H. (2016). Black cumin (Nigella sativa) and its active
Conclusions
constituent, thymoquinone: an overview on the analgesic and anti-inflam-
A number of therapeutic influences of N. sativa and TQ have been matory effects. Planta Medica, 82: 8–16.
scientifically investigated. This includes antidiabetic, anti-allergic, Arun, K. B., Aswathi, U., Venugopal, V. V., Madhavankutty, T. S., Nisha, P.
anti-microbial, immune-modulatory, anti-inflammatory, and anti- (2016). Nutraceutical properties of cumin residue generated from ayur-
tumour effects (Figure 4). Nigella sativa and TQ also possess gastro- vedic industries using cell line models. Journal of Food Science and
protective, hepatoprotective, nephroprotective, and neuroprotective Technology, 53: 3814–3824.
Aruna, K., Sivaramakrishnan, V. M. (1990). Plant products as protective agents
activities. The scientific studies conducted so far have confirmed
against cancer. Indian Journal of Experimental Biology, 28: 1008–1011.
the pharmacological potential of N.  sativa seeds, its oil, extracts,
Asgary, S., Sahebkar, A., Goli-Malekabadi, N. (2015). Ameliorative effects of
and its active principles, particularly TQ. TQ is the most abundant
Nigella sativa on dyslipidemia. Journal of Endocrinological Investigation,
constituent of the volatile oil of N.  sativa seeds, and most of the 38: 1039–1046.
medicinal properties of N. sativa are attributable mainly to TQ. All Assayed, M. E. (2010). Radioprotective effects of black seed (Nigella sativa)
the available evidence suggests that TQ should be developed as a oil against hemopoietic damage and immunosuppression in gamma-irra-
drug or adjuvant in clinical trials. Nigella sativa seeds, its oil, and diated rats. Immunopharmacology and Immunotoxicology, 32: 284–296.
14 K. Srinivasan, 2018, Vol. 2, No. 1

Balbaa, M., El-Zeftawy, M., Ghareeb, D., Taha, N., Mandour, A. W. (2016). Gilhotra, N., Dhingra, D. (2011). Thymoquinone produced antianxiety-
Nigella sativa relieves the altered insulin receptor signaling in streptozo- like effects in mice through modulation of GABA and NO levels.
tocin-induced diabetic rats fed with a high-fat diet. Oxidative Medicine Pharmacological Reports: PR, 63: 660–669.
and Cellular Longevity, 2016: 2492107. Goreja, W. G. (2003). Black Seed: Nature’s Miracle Remedy. New York,
Bamosa, A. O., Kaatabi, H., Lebdaa, F. M., Elq, A. M., Al-Sultanb, A. (2010). Effect Amazing Herbs Press.
of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes Hagag, A. A., AbdElaal, A. M., Elfaragy, M. S., Hassan, S. M., Elzamarany, E.
mellitus. Indian Journal of Physiology and Pharmacology, 54: 344–354. A. (2015). Therapeutic value of black seed oil in methotrexate hepatotox-
Bettaieb, I., Bourgou, S., Sriti, J., Msaada, K., Limam, F., Marzouk, B. (2011). icity in Egyptian children with acute lymphoblastic leukemia. Infectious
Essential oils and fatty acids composition of Tunisian and Indian cumin Disorders Drug Targets, 15: 64–71.
(Cuminum cyminum L.) seeds: a comparative study. Journal of the Science Hajhashemi, V., Ghannadi, A., Jafarabadi, H. (2004). Black cumin seed essen-

Downloaded from https://academic.oup.com/fqs/article/2/1/1/4823052 by University of Agriculture, Faisalabad user on 28 September 2022


of Food and Agriculture, 91: 2100–2107. tial oil, as a potent analgesic and antiinflammatory drug. Phytotherapy
Boskabady, M. H., Shirmohammadi, B. (2002). Effect of Nigella sativa on iso- Research: PTR, 18: 195–199.
lated guinea pig trachea. Archives of Iranian Medicine, 5: 103–107. Harzallah, H. J., Grayaa, R., Kharoubi, W., Maaloul, A., Hammami, M.,
Boskabady, M. H., Javan, H., Sajady, M., Rakhshandeh, H. (2007). The Mahjoub, T. (2012). Thymoquinone, the Nigella sativa bioactive com-
possible prophylactic effect of Nigella sativa seed extract in asthmatic pound, prevents circulatory oxidative stress caused by 1,2-dimethylhydra-
patients. Fundamental & Clinical Pharmacology, 21: 559–566. zine in erythrocyte during colon postinitiation carcinogenesis. Oxidative
Chehl, N., Chipitsyna, G., Gong, Q., Yeo, C. J., Arafat, H. A. (2009). Anti- Medicine and Cellular Longevity, 2012: 854065.
inflammatory effects of the Nigella sativa seed extract, thymoquinone, Hayatdavoudi, P., Khajavi Rad, A., Rajaei, Z., Hadjzadeh, M. A. (2016). Renal
in pancreatic cancer cells. HPB: the Official Journal of the International injury, nephrolithiasis and Nigella sativa: a mini review. Avicenna Journal
Hepato Pancreato Biliary Association, 11: 373–381. of Phytomedicine, 6: 1–8.
Cheikh-Rouhou, S., Besbes, S., Lognay, G., Blecker, C., Deroanne, C., Attia, H. Hosseinzadeh, H., Parvardeh, S., Asl, M. N., Sadeghnia, H. R., Ziaee, T.
(2008). Sterol composition of black cumin (Nigella sativa L.) and aleppo (2007). Effect of thymoquinone and Nigella sativa seeds oil on lipid per-
pine (Pinus halpensis Mill.) seed oils. Journal of Food Composition and oxidation level during global cerebral ischemia-reperfusion injury in rat
Analysis, 21: 162–168. hippocampus. Phytomedicine: International Journal of Phytotherapy and
Cüce, G., Sözen, M. E., Çetinkaya, S., Canbaz, H. T., Seflek, H., Kalkan, S. Phytopharmacology, 14: 621–627.
(2015). Effects of Nigella sativa L. seed oil on intima-media thickness and Isik, F., et  al. (2011). Protective effects of black cumin (Nigella sativa) oil
Bax and Caspase-3 expression in diabetic rat aorta. Anatolian Journal of on TNBS-induced experimental colitis in rats. Digestive Diseases and
Cardiology, 16: 460–446. Sciences, 56: 721–730.
Dandapani, S., Subramanian, V. R., Rajagopal, S., Namasivayam, N. (2002). Jagtap, A. G., Patil, P. B. (2010). Antihyperglycemic activity and inhibition
Hypolipidemic effect of Cuminum cyminum L. on alloxan-induced dia- of advanced glycation end product formation by Cuminum cyminum
betic rats. Pharmacological Research, 46: 251–255. in streptozotocin induced diabetic rats. Food and Chemical Toxicology:
Duncker, S. C., Philippe, D., Martin-Paschoud, C., Moser, M., Mercenier, A., An International Journal Published for the British Industrial Biological
Nutten, S. (2012). Nigella sativa (black cumin) seed extract alleviates Research Association, 48: 2030–2036.
symptoms of allergic diarrhea in mice, involving opioid receptors. Plos Kalaivani, P., et  al. (2013). Cuminum cyminum, a dietary spice, attenuates
One, 7: e39841. hypertension via endothelial nitric oxide synthase and no pathway in
El-Abhar, H. S., Abdallah, D. M., Saleh, S. (2003). Gastroprotective activ- renovascular hypertensive rats. Clinical and Experimental Hypertension
ity of Nigella sativa oil and its constituent, thymoquinone, against gas- (New York, N.Y.: 1993), 35: 534–542.
tric mucosal injury induced by ischaemia/reperfusion in rats. Journal of Kaleem, M., Kirmani, D., Asif, M., Ahmed, Q., Bano, B. (2006). Biochemical
Ethnopharmacology, 84: 251–258. effects of Nigella sativa L.  seeds in diabetic rats. Indian Journal of
El-Dakhakhny, M., Mady, N., Lembert, N., Ammon, H. P. (2002). The hypo- Experimental Biology, 44: 745–748.
glycemic effect of Nigella sativa oil is mediated by extrapancreatic actions. Kanter, M., et al. (2003). Effects of Nigella sativa L. and urtica dioica L. on
Planta Medica, 68: 465–466. lipid peroxidation, antioxidant enzyme systems and some liver enzymes in
Fararh, K. M., Atoji, Y., Shimizu, Y., Takewaki, T. (2002). Isulinotropic proper- ccl4-treated rats. Journal of Veterinary Medicine. A, Physiology, Pathology,
ties of Nigella sativa oil in streptozotocin plus nicotinamide diabetic ham- Clinical Medicine, 50: 264–268.
ster. Research in Veterinary Science, 73: 279–282. Kanter, M., Coskun, O., Korkmaz, A., Oter, S. (2004). Effects of Nigella sativa
Fararh, K. M., Atoji, Y., Shimizu, Y., Shiina, T., Nikami, H., Takewaki, T. on oxidative stress and beta-cell damage in streptozotocin-induced dia-
(2004). Mechanisms of the hypoglycaemic and immunopotentiating betic rats. The Anatomical Record. Part A, Discoveries in Molecular,
effects of Nigella sativa L. Oil in streptozotocin-induced diabetic hamsters. Cellular, and Evolutionary Biology, 279: 685–691.
Research in Veterinary Science, 77: 123–129. Kanter, M., Akpolat, M., Aktas, C. (2009). Protective effects of the volatile
Gagandeep, Dhanalakshmi, S., Méndiz, E., Rao, A. R., Kale, R. K. (2003). oil of Nigella sativa seeds on beta-cell damage in streptozotocin-induced
Chemopreventive effects of Cuminum cyminum in chemically induced diabetic rats: a light and electron microscopic study. Journal of Molecular
forestomach and uterine cervix tumors in murine model systems. Nutrition Histology, 40: 379–385.
and Cancer, 47: 171–180. Kanter, M. (2009). Effects of Nigella sativa seed extract on ameliorating lung
Gali-Muhtasib, H., Roessner, A., Schneider-Stock, R. (2006). Thymoquinone: tissue damage in rats after experimental pulmonary aspirations. Acta
a promising anti-cancer drug from natural sources. The International Histochemica, 111: 393–403.
Journal of Biochemistry & Cell Biology, 38: 1249–1253. Kapoor, S. (2009). Emerging clinical and therapeutic applications of nigella sativa
Gendy, E., Hessien, M., Abdel Salamm, I., Moradm, M. E. L., Magrabym, K., in gastroenterology. World Journal of Gastroenterology, 15: 2170–2171.
Ibrahimm, H. A., et al. (2007). Evaluation of the possible antioxidant effects Karnick, C. R. (1991). A clinical trial of a composite herbal drug in the treat-
of Soybean and Nigella sativa during experimental hepatocarcinogenesis by ment of diabetes me1litus. Aryavaidyan, 5: 36–46.
nitrosamine precursors. Turkish Journal of Biochemistry, 32: 5–11. Khaled, A. A. S. (2009). Gastroprotective effects of Nigella sativa oil on the
Gholamnezhad, Z., Havakhah, S., Boskabady, M. H. (2016). Preclinical and formation of stress gastritis in hypothyroidal rats. International Journal of
clinical effects of Nigella sativa and its constituent, thymoquinone: a Physiology Pathophysiology and Pharmacology, 1: 143–149.
review. Journal of Ethnopharmacology, 190: 372–386. Khan, N., Sultana, S. (2005). Inhibition of two stage renal carcinogenesis, oxi-
Ghonime, M., Eldomany, R., Abdelaziz, A., Soliman, H. (2011). Evaluation dative damage and hyperproliferative response by Nigella sativa. European
of immunomodulatory effect of three herbal plants growing in Egypt. Journal of Cancer Prevention: the Official Journal of the European Cancer
Immunopharmacology and Immunotoxicology, 33: 141–145. Prevention Organisation (ecp), 14: 159–168.
Nutraceutical effects of cumin and black cumin seeds, 2018, Vol. 2, No. 1  15

Khan, M. A., Chen, H. C., Tania, M., Zhang, D. Z. (2011). Anticancer Nalini, N., Manju, V., Menon, V. P. (2006). Effect of spices on lipid metabol-
activities of Nigella sativa (black cumin). African Journal of Traditional, ism in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Journal of
Complementary, and Alternative Medicines: AJTCAM, 8: 226–232. Medicinal Food, 9: 237–245.
Khan, S. A., Khan, A. M., Karim, S., Kamal, M. A., Damanhouri, G. A., Mirza, Ng, W. K., Yazan, L. S., Ismail, M. (2011). Thymoquinone from Nigella sativa
Z. (2016). Panacea seed “nigella”: a review focusing on regenerative effects was more potent than cisplatin in eliminating of siha cells via apoptosis with
for gastric ailments. Saudi Journal of Biological Sciences, 23: 542–553. down-regulation of bcl-2 protein. Toxicology in Vitro: An International
Lee, H. S. (2005). Cuminaldehyde: aldose reductase and alpha-glucosidase Journal Published in Association with BIBRA, 25: 1392–1398.
inhibitor derived from Cuminum cyminum L. seeds. Journal of Agricultural Nickavar, B., Mojab, F., Javidnia, K., Amoli, M. A. (2003). Chemical compos-
and Food Chemistry, 53: 2446–2450. ition of the fixed and volatile oils of Nigella sativa L. from Iran. Zeitschrift
Lei, X., Liu, M., Yang, Z., Ji, M., Guo, X., Dong, W. (2012). Thymoquinone Fur Naturforschung. C, Journal of Biosciences, 58: 629–631.

Downloaded from https://academic.oup.com/fqs/article/2/1/1/4823052 by University of Agriculture, Faisalabad user on 28 September 2022


prevents and ameliorates dextran sulfate sodium-induced colitis in mice. Nikakhlagh, S., Rahim, F., Aryani, F. H., Syahpoush, A., Brougerdnya, M. G.,
Digestive Diseases and Sciences, 57: 2296–2303. Saki, N. (2011). Herbal treatment of allergic rhinitis: the use of Nigella
Lei, X., et  al. (2012). Thymoquinone inhibits growth and augments sativa. American Journal of Otolaryngology, 32: 402–407.
5-­fluorouracil-induced apoptosis in gastric cancer cells both in vitro Pari, L., Sankaranarayanan, C. (2009). Beneficial effects of thymoquinone on
and in vivo. Biochemical and Biophysical Research Communications, hepatic key enzymes in streptozotocin-nicotinamide induced diabetic rats.
417: 864–868. Life Sciences, 85: 830–834.
Li, R., Jiang, Z. (2004). Chemical composition of the essential oil of Cuminum Peng, L., et al. (2013). Antitumor and anti-angiogenesis effects of thymoqui-
cyminum L. from China. Flavour and Fragrance Journal, 19: 311–313. none on osteosarcoma through the NF-κb pathway. Oncology Reports,
Linjawi, S. A., Khalil, W. K., Hassanane, M. M., Ahmed, E. S. (2015). 29: 571–578.
Evaluation of the protective effect of Nigella sativa extract and its primary Perveen, T., Abdullah, A., Haider, S., Sonia, B., Munawar, A. S., Haleem, D. J.
active component thymoquinone against DMBA-induced breast cancer in (2008). Long-term administration of Nigella sativa effects nociceotion and
female rats. Archives of Medical Science: AMS, 11: 220–229. improves learning and memory in rats. Pakistan Journal of Biochemistry
Magdy, M. A., Hanan, e. l.  -. A., Nabila, e. l.  -. M. (2012). Thymoquinone: and Molecular Biology, 41: 141–143.
novel gastroprotective mechanisms. European Journal of Pharmacology, Perveen, T., Haider, S., Kanwal, S., Haleem, D. J. (2009). Repeated adminis-
697: 126–131. tration of Nigella sativa decreases 5-HT turnover and produces anxiolytic
Mahmoud, S. S., Torchilin, V. P. (2012). Hormetic/cytotoxic effects of Nigella effects in rats. Pakistan Journal of Pharmaceutical Sciences, 22: 139–144.
sativa seed alcoholic and aqueous extracts on MCF-7 breast cancer cells Platel, K., Srinivasan, K. (1996). Influence of dietary spices or their active prin-
alone or in combination with doxorubicin. Cellular Biochemistry and ciples on digestive enzymes of small intestinal mucosa in rats. International
Biophysics, 25: 1392–1398. Journal of Food Sciences and Nutrition, 47: 55–59.
Majdalawieh, A. F., Fayyad, M. W. (2015). Immunomodulatory and Platel, K., Srinivasan, K. (2000a). Influence of dietary spices and their active
anti-inflammatory action of Nigella sativa and thymoquinone: a compre- principles on pancreatic digestive enzymes in albino rats. Die Nahrung,
hensive review. International Immunopharmacology, 28: 295–304. 44: 42–46.
Majdalawieh, A. F., Fayyad, M. W. (2016). Recent advances on the anti-can- Platel, K., Srinivasan, K. (2000b). Stimulatory influence of select spices on bile
cer properties of Nigella sativa, a widely used food additive. Journal of secretion in rats. Nutrition Research, 20: 1493–1503.
Ayurveda and Integrative Medicine, 7: 173–180. Platel, K., Srinivasan, K. (2001). Studies on the influence of dietary spices on
Mansour, M., Tornhamre, S. (2004). Inhibition of 5-lipoxygenase and leuko- food transit time in experimental rats. Nutrition Research, 21: 1493–1503.
triene C4 synthase in human blood cells by thymoquinone. Journal of Rchid, H., et al. (2004). Nigella sativa seed extracts enhance glucose-induced
Enzyme Inhibition and Medicinal Chemistry, 19: 431–436. insulin release from rat-isolated langerhans islets. Fundamental & Clinical
Mehta, B. K., Verma, M., Gupta, M. J. (2008). Novel lipid constituents identi- Pharmacology, 18: 525–529.
fied in seeds of Nigella sativa Linn. Journal of Brazilian Chemical Society, Roman-Ramos, R., Flores-Saenz, J. L., Alarcon-Aguilar, F. J. (1995). Anti-
19: 458–462. hyperglycemic effect of some edible plants. Journal of Ethnopharmacology,
Meral, I., Yener, Z., Kahraman, T., Mert, N. (2001). Effect of Nigella sativa on glu- 48: 25–32.
cose concentration, lipid peroxidation, anti-oxidant defence system and liver Sahebkar, A., et al. (2016a). A systematic review and meta-analysis of rand-
damage in experimentally-induced diabetic rabbits. Journal of Veterinary omized controlled trials investigating the effects of supplementation with
Medicine. A, Physiology, Pathology, Clinical Medicine, 48: 593–599. Nigella sativa (black seed) on blood pressure. Journal of Hypertension,
Mnif, S., Aifa, S. (2015). Cumin (Cuminum cyminum L.) from traditional 34: 2127–2135.
uses to potential biomedical applications. Chemistry & Biodiversity, 12: Sahebkar, A., Beccuti, G., Simental-Mendía, L. E., Nobili, V., Bo, S. (2016b).
733–742. Nigella sativa (black seed) effects on plasma lipid concentrations in
Mohtashami, A., Entezari, M. H. (2016). Effects of Nigella sativa supplemen- humans: a systematic review and meta-analysis of randomized placebo-
tation on blood parameters and anthropometric indices in adults: a sys- controlled trials. Pharmacological Research, 106: 37–50.
tematic review on clinical trials. Journal of Research in Medical Sciences: Sahoo, H. B., Sahoo, S. K., Sarangi, S. P., Sagar, R., Kori, M. L. (2014). Anti-
the Official Journal of Isfahan University of Medical Sciences, 21: 3. diarrhoeal investigation from aqueous extract of Cuminum cyminum linn.
Morshedi, D., Aliakbari, F., Tayaranian-Marvian, A., Fassihi, A., Pan-Montojo, Seed in albino rats. Pharmacognosy Research, 6: 204–209.
F., Pérez-Sánchez, H. (2015). Cuminaldehyde as the major component of Saleem, U., Ahmad, B., Rehman, K., Mahmood, S., Alam, M., Erum, A. (2012).
Cuminum cyminum, a natural aldehyde with inhibitory effect on alpha- Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin
synuclein fibrillation and cytotoxicity. Journal of Food Science, 80: associated nephrotoxicity in rabbits. Pakistan Journal of Pharmaceutical
H2336–H2345. Sciences, 25: 727–730.
Morsi, N. M. (2000). Antimicrobial effect of crude extracts of nigella sativa Salim, E. I., Fukushima, S. (2003). Chemopreventive potential of volatile oil
on multiple antibiotics-resistant bacteria. Acta Microbiologica Polonica, from black cumin (Nigella sativa L.) seeds against rat colon carcinogen-
49: 63–74. esis. Nutrition and Cancer, 45: 195–202.
Mousavi, G. (2015). Study on the effect of black cumin (Nigella sativa Linn.) Salim, E. I. (2010). Cancer chemopreventive potential of volatile oil from black
On experimental renal ischemia-reperfusion injury in rats. Acta Cirurgica cumin seeds, Nigella sativa l., in a rat multi-organ carcinogenesis bioassay.
Brasileira, 30: 542–550. Oncology Letters, 1: 913–924.
Najmi, A., Haque, S. F., Naseeruddin, M., Khan, R. A. (2008). Effect of Nigella Samani, K. G., Farrokhi, E. (2014). Effects of cumin extract on oxldl, paraoxa-
sativa oil on various clinical and biochemical parameters of metabolic nase 1 activity, FBS, total cholesterol, triglycerides, HDL-C, LDL-C, apo
syndrome. International Journal of Diabetes in Developing Countries, 16: A1, and apo B in in the patients with hypercholesterolemia. International
85–87. Journal of Health Sciences, 8: 39–43.
16 K. Srinivasan, 2018, Vol. 2, No. 1

Sambaiah, K., Srinivasan, K. (1991). Effect of cumin, cinnamon, ginger, mus- Uz, E., et al. (2008). Nigella sativa oil for prevention of chronic cyclosporine
tard and tamarind in induced hypercholesterolemic rats. Die Nahrung, nephrotoxicity: an experimental model. American Journal of Nephrology,
35: 47–51. 28: 517–522.
Sayed-Ahmed, M. M., Nagi, M. N. (2007). Thymoquinone supplementa- Wei, J., Zhang, X., Bi, Y., Miao, R., Zhang, Z., Su, H. (2015). Anti-
tion prevents the development of gentamicin-induced acute renal tox- inflammatory effects of cumin essential oil by blocking JNK, ERK,
icity in rats. Clinical and Experimental Pharmacology & Physiology, 34: and NF-κb signaling pathways in LPS-stimulated RAW 264.7 cells.
399–405. Evidence-Based Complementary and Alternative Medicine: Ecam,
Shafi, G., Hasan, T. N., Sayed, N. A. (2008). Methanolic extracts of Nigella 2015: 474509.
sativa seed as potent lonogenic inhibitor of PC-3 cells. International Willatgamuwa, S. A., Platel, K., Saraswathi, G., Srinivasan, K. (1998). Anti-
Journal of Pharmacology, 4: 477–481. diabetic influence of dietary cumin seeds (Cuminum cyminum) in strepto-

Downloaded from https://academic.oup.com/fqs/article/2/1/1/4823052 by University of Agriculture, Faisalabad user on 28 September 2022


Sharma, P. C., Yelne, M. B., Dennis, T. J. (2005). Database on Medicinal Plants zotocin induced diabetic rats. Nutrition Research, 18: 131–142.
Used in Ayurveda. Central Council for Research in Ayurveda & Siddha, Woo, C. C., et  al. (2011). Anticancer activity of thymoquinone in breast
New Delhi. pp. 420–440. cancer cells: possible involvement of PPAR-γ pathway. Biochemical
Shuid, A. N., et al. (2012). Nigella sativa: a potential antiosteoporotic agent. Pharmacology, 82: 464–475.
Evidence-Based Complementary and Alternative Medicine: Ecam, 2012: Wu, Z. H., Chen, Z., Shen, Y., Huang, L. L., Jiang, P. (2011). [Anti-metastasis
696230. effect of thymoquinone on human pancreatic cancer]. Yao Xue Bao = Acta
Sogut, B., Celik, I., Tuluce, Y. (2008). The effects of diet supplemented with Pharmaceutica Sinica, 46: 910–914.
the black Cumin (Nigella sativa L.) upon immune potential and antioxi- Yaman, I., Balikci, E. (2010). Protective effects of Nigella sativa against gen-
dant marker enzymes and lipid peroxidation in broiler chicks. Journal of tamicin-induced nephrotoxicity in rats. Experimental and Toxicologic
Animal and Veterinary Advances, 7: 1196–1199. Pathology: Official Journal of the Gesellschaft Fur Toxikologische
Taka, E., et al. (2015). Anti-inflammatory effects of thymoquinone in activated Pathologie, 62: 183–190.
bv-2 microglial cells. Journal of Neuroimmunology, 286: 5–12. Yarnell, E., Abascal, K. (2011). Nigella sativa: holy herb of the Middle East.
Tayman, C., et al. (2013). Protective effects of Nigella sativa oil in hyperoxia- Alternative and Complementary Therapy, 17: 99–105.
induced lung injury. Archivos De Bronconeumologia, 49: 15–21. Yi, T., et  al. (2008). Thymoquinone inhibits tumor angiogenesis and
Tayman, C., et al. (2012). Beneficial effects of Nigella sativa oil on intestinal tumor growth through suppressing AKT and extracellular signal-reg-
damage in necrotizing enterocolitis. Journal of Investigative Surgery: the ulated kinase signaling pathways. Molecular Cancer Therapeutics, 7:
Official Journal of the Academy of Surgical Research, 25: 286–294. 1789–1796.
Torres, M. P., et al. (2010). Effects of thymoquinone in the expression of mucin Yildiz, F., et al. (2008). Nigella sativa relieves the deleterious effects of ische-
4 in pancreatic cancer cells: implications for the development of novel can- mia reperfusion injury on liver. World Journal of Gastroenterology, 14:
cer therapies. Molecular Cancer Therapeutics, 9: 1419–1431. 5204–5209.
Ulu, R., et  al. (2012). Regulation of renal organic anion and cation trans- Yildiz, F., et  al. (2010). Protective effects of Nigella sativa against ischemia-
porters by thymoquinone in cisplatin induced kidney injury. Food and reperfusion injury of kidneys. Renal Failure, 32: 126–131.
Chemical Toxicology: An International Journal Published for the British Yuan, T., et  al. (2014). Indazole-type alkaloids from Nigella sativa seeds
Industrial Biological Research Association, 50: 1675–1679. exhibit antihyperglycemic effects via AMPK activation in vitro. Journal of
Umar, S., Zargan, J., Umar, K., Ahmad, S., Katiyar, C. K., Khan, H. A. (2012). Natural Products, 77: 2316–2320.
Modulation of the oxidative stress and inflammatory cytokine response by Zafeer, M. F., Waseem, M., Chaudhary, S., Parvez, S. (2012). Cadmium-
thymoquinone in the collagen induced arthritis in wistar rats. Chemico- induced hepatotoxicity and its abrogation by thymoquinone. Journal of
Biological Interactions, 197: 40–46. Biochemical and Molecular Toxicology, 26: 199–205.

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