November-December 2018 Indian Journal of Pharmaceutical Sciences 971
Nigella sativa L. (Ranunculaceae) is an annual
owering plant with green-to-blue-colored owers and
black seeds, native to southwest Asia, southern Europe
and North Africa but it is cultivated and used in other
parts of the world.
Crude oil derived from the seeds of N. sativa
exhibited a variety of pharmacological effects such
as antihistaminic[2,3], anticholinergic, diuretic and
antihypertensive[5,6], hypoglycemic, antioxytocic,
antinociceptive, respiratory stimulator, antiasthma
and antidyspnea, antitussive, bronchodilatory,
tracheal smooth muscle relaxant[14,15], hematological,
anticancer, antimicrobial, antiinammatory[20,21],
antifungal, antiulcer and antioxidant. N. sativa
seed oil is also effective in treating headache, atulence,
blood homeostasis abnormalities, rheumatism and
related inammatory diseases. Chemical composition
of N. sativa seed extracts analysed by supercritical CO2
extraction included n-nonane, tricyclene, camphene,
β-pinene, β-myrcene, 1,8-cineole, α-terpinene,
limonene, linalool, terpinolene, borneol, pinocarvone,
thymoquinone (TQ), thymol, carvacrol, cyclosativene,
α-longicyclene, palmitic acid, octadecanoic acid,
dihydrofarnesyl acetate, davanone and dihydrofarnesyl
acetate. Pharmacological properties of N. sativa
could be attributed to the constituents like nigellicine,
nigellidine, TQ, dithymoquinone, thymol, and
carvacrol (g. 1). Alimohammadi et al. reported
that the extract of N. sativa reduced blood glucose
due to inhibition of hepatic gluconeogenesis and
possible insulin tropic properties. Treatment with N.
sativa markedly decreased the fasting blood glucose
(FBG) level in streptozotocin (STZ) diabetic rats.
Histopathological examination also indicated that
the N. sativa partially ameliorated hepatic glycogen
content and preserved the pancreatic islet cells.
In addition, extracts of N. sativa and its constituents
Cardiovascular Effects of Nigella Sativa L. and its
F. SHAKERI, M. KHAZAEI1,2 AND M. H. BOSKABADY1,2*
Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, 1Neurogenic
Inammation Research Center, Mashhad University of Medical Sciences, 2Department of Physiology, School of Medicine,
Mashhad University of Medical Sciences, Mashhad, Iran
Shakeri, et al.: Cardiovascular effects of Nigella sativa
Various pharmacological effects of Nigella sativa L. have been reported that include, antioxidant,
antibacterial, antihistaminic, antihypertensive, hypoglycemic, antifungal, antiinﬂammatory, anticancer, and
immunomodulatory. It has also been reported to produce benecial effects in cardiovascular, gastrointestinal,
reproductive and respiratory disorders. The effects of Nigella sativa had been attributed to constituents
such as nigellicine, nigellidine, thymoquinone, dithymoquinone, thymol and carvacrol. In this article the
cardiovascular effects of Nigella sativa and its constituents were reviewed. Published data was gathered
through search engines and the ndings were classied into animal and human studies. The effects of
Nigella sativa and its constituents on cardiotoxicity, blood pressure, vascular smooth muscle, endothelial
dysfunction, heart rate, cardiac contractility, lipid prole, platelet aggregation and atherosclerosis were
reviewed. This review indicated that Nigella sativa and thymoquinone exhibited benecial cardiovascular
effects on cardiotoxicity, hypertension, hyperlipidemia, and atherosclerosis. These effects were probably
due to the antioxidant and antiinﬂammatory properties of Nigella sativa. It seems that Nigella sativa and its
constituents could be of therapeutic value in cardiovascular diseases.
Key words: Thymoquinone, cardiovascular disease, hypertension, atherosclerosis, hyperlipidemia
*Address for correspondence
This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which
allows others to remix, tweak, and build upon the work non-commercially,
as long as the author is credited and the new creations are licensed under
the identical terms
Accepted 03 September 2018
Revised 08 August 2017
Received 08 December 2016
Indian J Pharm Sci 2018;80(6):971-983
Indian Journal of Pharmaceutical Sciences
could lower blood pressure through blockade of
calcium channels[29,30]. The plant also showed a potent
inhibitory effect on both heart rate and contractility of
isolated guinea pig heart comparable and even higher
than that of diltiazem[31,32]. In the present review, the
cardiovascular effects of N. sativa and its constituents
Online literature searches were performed using
Medline, PubMed, Science Direct, Scopus, and
Google Scholar websites from 1965 to 2015 to identify
studies about cardiovascular effects of N. sativa and
its constituents. The keywords used were; N. sativa,
cardiovascular, cardiotoxicity, blood pressure, vascular
smooth muscle, endothelial dysfunction, heart rate,
heart contractility, lipid prole, platelet aggregation,
and atherosclerosis. The search results were checked
by two authors and cited articles were reviewed by
authors. Therefore, the risk of bias within the studies
and across the studies as far as this review concern was
avoided. There was no obvious limitation at the review
level. However, only few studies were found regarding
the clinical effect of the plant and its constituents
on cardiovascular diseases. Therefore, only limited
information at the outcome level could be presented in
LABORATORY ANIMAL STUDIES
Effect on cardiotoxicity:
Treatment with N. sativa seed powder (4 % w/w) and/or
aqueous solution of bees’ honey (2.5 g/kg/day) showed
a protective effect on the heart disorder induced by food
additives in rats. Cardioprotective effect of N. sativa
seed oil administered 4 ml/kg orally, 1 h before the
administration of lead acetate 20 mg/kg, intraperitoneal
(ip) 3 d weekly for 8 w on lead-induced cardiotoxicity in
rats has been reported. Findings showed that N. sativa
seed oil decreased heart rate, changes in ST segment,
which is the isoelectric section of the ECG between
the end of the S wave and the beginning of the T wave
also known as the J point, proinammatory cytokine
levels, oxidative stress and cardiac tissue damage.
Pretreatment with N. sativa oil (2 ml/kg, per oral, po) in
cyclosporine A-induced cardiomyopathy (25 mg/kg, po)
in rats for three weeks decreased the cyclosporine A
injury in the heart and lipid peroxidation, normalized
cardiac histopathology, improved antioxidant enzyme
status and cellular protein oxidation. Pretreatment
with TQ (100 mg/kg, po) and N. sativa seed oil
(100 µl/kg) reduced the plasma levels of triglycerides,
lipid peroxidation, cholesterol, glutathione peroxidase
and superoxide dismutase (SOD) activities on
methionine-induced hyperhomocysteinemia in rats.
The cardioprotective effect of TQ (50 mg/l in
drinking water), the main constituent of the volatile
oil of N. sativa seed, on cyclophosphamide-induced
cardiotoxicity in albino rats was evaluated by
Nagi et al. in 2011. Findings showed that treatment
with TQ caused a complete reversal of all the
biochemical changes induced by cyclophosphamide
and decreased oxidative and nitrosative stress as well
as improved antioxidant enzyme status, mitochondrial
function and energy production in heart tissues. The
effect of TQ (8-10 mg/kg/day, po) on doxorubicin-
induced cardiotoxicity (15-20 mg/kg as a single ip
injection) was also demonstrated that TQ when given
in the drinking water protects rats from doxorubicin-
induced cardiotoxicity as evidenced by signicant
reductions in serum lactate dehydrogenase and
creatine kinase. The superoxide scavenging, antilipid
peroxidation and cytoprotective agent may explain
such effect[38,39]. The protective effect of TQ (5, 10 and
20 mg/kg/day) on cypermethrin-induced (10 mg/kg/
day, po) necrosis, degeneration, and loss of striation in
heart for 28 d in albino mice showed that treatment with
TQ caused reversal of all biochemical changes induced
by cypermethrin and decreased oxidative stress lipid
The protective effect of TQ on the acute (at 4 and
18 h) effects of diesel exhaust particles (DEP,
30 mg/mouse, intratracheal) on cardiopulmonary
parameters in mice also showed that pretreatment of
C D E
Fig. 1: Chemical structure of some potentially bioactive
compounds in N. sativa
A: Thymoquinone; B: dithymoquinone; C: thymohydroquinone;
D: thymol; E: p-cymene
Indian Journal of Pharmaceutical Sciences 973
mice with TQ (6 mg/kg, ip), 24 and 1 h before DEP,
decreased IL-6 concentration, leukocytosis, airway
hyperresponsiveness to methacholine and increased
systolic blood pressure (SBP), platelet numbers,
plasma SOD activity. The effect of TQ (12.5, 25 and
50 mg/kg, po) on isoproterenol-induced myocardial
injury in rats showed that TQ decreased plasma SOD
activity, myocardial glutathione (GSH)/glutathione
disulphide ratio and histological changes induced
by isoproterenol. The effects of N. sativa and its
constituents on cardiotoxicity were summarized in
Effect on blood pressure:
The diuretic and hypotensive effects of dichloromethane
extract of N. sativa in the spontaneously hypertensive
rat indicated that oral administrations of N. sativa
extract (0.6 ml/kg/day) and furosemide (5 mg/kg/
day) signicantly increased the diuresis by 16 and
30 %, respectively after 15 d of treatment and reduced
the mean arterial pressure (MAP) by 22 and 18 %,
respectively. The protective effect of N. sativa
(0.2 ml/kg/day, ip) against oxidative injury in the
heart and kidney tissues of rats with renovascular
hypertension model induced by placing a renal artery
clip was investigated. The ndings showed that
N. sativa signicantly reduced blood pressure,
attenuated oxidative injury and improved left
ventricular function. The results also suggested that
N. sativa protected against hypertension-induced
tissue damage and improved cardiovascular function
by its antioxidant and antihypertensive effects. The
effect of N. sativa on L-NAME-induced hypertensive
rats also showed that oral administration of N. sativa
(2.5 ml/kg/day) reduced SBP and diastolic blood
pressure (DBP). The results also suggested that this
effect of N. sativa may be mediated by stimulating
nitric oxide release from vascular endothelium.
The volatile oil of the N. sativa seed (4-32 µl/kg,
intravenous, iv) reduced arterial blood pressure and
heart rate in a dose-dependent manner in guinea-
pigs. The effect of aqueous extract of N. sativa on
spontaneously hypertensive rats was also showed that
N. sativa signicantly reduced SBP and increased
urinary output and glomerular ltration rate. These
results also suggested that the antihypertensive effect
of N. sativa is mediated by increasing urinary and
electrolyte output. The effects of N. sativa seeds and
Syzygium aromaticum extracts on L-NAME-induced
hypertensive rats showed that N. sativa (400 mg/kg)
and S. aromaticum (100 mg/kg) reduced SBP, DBP,
MAP, LDL and increased serum nitric oxide level.
The effect of volatile oil of the N. sativa seed and TQ
on the arterial blood pressure and heart of urethane-
anaesthetized rats showed that treatment with volatile
oil of N. sativa seed (4-32 µl/kg, iv) or TQ (0.2-1.6
mg/kg, iv) decreased the arterial blood pressure and the
heart rate in a dose-dependent manner. The protective
effect of TQ (0.5 and 1 mg/kg/day, po), on L-NAME-
induced hypertension (50 mg/kg/day, po) for 4 w in
rats was evaluated by Khattab et al. in 2007 and the
ndings showed that TQ reduced the increase in SBP
induced by L-NAME in a dose-dependent manner and
decreased the elevated creatinine and increased GSH to
normal levels. The hypotensive effect of α-pinene (1,
5, 10, and 20 mg/kg, iv), a constituent of the essential
oil of N. sativa seed was seen in non-anaesthetized
normotensive rats. Dethymoquinonated volatile of
N. sativa seed, α-pinene and p-cymene also in a dose
range (2-16 µl/kg, iv) reduced blood pressure and heart
rate in urethane-anaesthetized rats, which is mediated
by inhibition of vasomotor center. The effects of
N. sativa and its constituents on blood pressure are
summarized in Table 1.
Effect on vascular smooth muscle and endothelial
The essential oil from the seeds of N. sativa exhibited
a depressant effect on the frog heart and a relaxant
property on isolated vascular smooth muscles of rat.
The vasorelaxation effect of cumulative concentration
of the hydro-ethanolic extract of N. sativa (2, 4, 6, 8, 10,
and 14 mg/ml) on rat aortic smooth muscle contracted
by both KCl and phenylephrine was shown. In the
other study by Suddek in 2010, the effect of TQ on
smooth muscle of pulmonary artery was investigated.
TQ caused a concentration-dependent decrease in
the tension of the pulmonary arterial smooth muscles
precontracted by phenylephrine. Furthermore, the
relaxant effect of N. sativa may be mediated by the
activation of ATP-sensitive potassium channels and
probably by non-competitive blocking of serotonin,
alpha1 and endothelin receptors.
Endothelial dysfunction with ageing is due to the
endothelial release of vasoconstrictor prostaglandins
and imbalance between the production of NO and
endothelium-derived hyperpolarizing factor. The
oral administration of TQ (10 mg/kg/day) improved
endothelial function by inhibition of oxidative stress
and normalization of the angiotensin system in rat
Indian Journal of Pharmaceutical Sciences
mesenteric artery. The effects of N. sativa and its
constituents on vascular smooth muscle and endothelial
dysfunction were summarized in Table 2.
Effect on heart rate and heart contractility:
The effects of aqueous and macerated extracts from
N. sativa (0.5, 1.0, 2.0 and 5.0 mg, %) on heart rate and
contractility of isolated heart in guinea pig showed a
potent inhibitory effect of both extracts from N. sativa on
heart rate and contractility, which was comparable and
even higher than that of diltiazem. It is suggested that
two probable mechanisms for these effects are calcium
channel blocking and an opening effect of the plant
on potassium channels of the isolated heart[31,32]. The
effect of oral administration of N. sativa (800 mg/kg)
on intrinsic cardiac responses showed that N. sativa
TABLE 1: THE EFFECT OF N. SATIVA AND ITS CONSTITUENTS ON CARDIOTOXICITY AND BLOOD
Plant preparation Study model Effect Reference
N. sativa and honey Sodium nitrite and sunset yellow-
induced heart disorder
Modulating heart disorder induced by
food additives 
N. sativa oil Lead-induced cardiotoxicity in rat
Decreased heart rate, ST segment
change, pro inammatory cytokines,
oxidative stress and cardiac tissue
N. sativa oil Cyclosporine A-induced cardiomyopathy
Normalized cardiac histopathology,
decreased lipid peroxidation, improved
antioxidant enzyme status and cellular
N. sativa oil and TQ Methionine-induced
hyperhomocysteinemia in rat Decreased TG, lipid peroxidation and TC 
cardiotoxicity in rat
Decreased oxidative and nitrosative
stress, improved antioxidant enzyme
status and mitochondrial function in
TQ Doxorubicin-induced cardiotoxicity in
Reduced serum lactate dehydrogenase
and creatine kinase [38-39]
TQ Cypermethrin-induced cardio toxicity
Decreased oxidative stress and lipid
TQ Diesel exhaust particles-induced
cardiotoxicity in rat
Decreased of SBP, leucocytosis, platelet
counts and the prothrombotic activity,
increased IL-6 concentration and
decreased plasma SOD activity
TQ Isoproterenol-induced myocardial injury
Decreased plasma SOD activity,
myocardial GSH/GSSG ratio and
N. sativa RVH model in rat Reduced BP, oxidative injury, improved
left ventricular function 
N. sativa L-NAME-induced hypertension in rat Reduced SBP and DBP 
N. sativa and S.
aromaticum extract L-NAME-induced hypertension in rat Reduced SBP, DBP, MAP, LDL, increased
serum nitric oxide 
Aqueous extract Spontaneously hypertensive rat
Increased urinary output and glomerular
Dichloromethane extract Spontaneously hypertensive rat Increased the diuresis, reduced MAP 
Volatile oil Normotensive guinea pigs Reduced BP and heart rate in a dose
dependent manner 
Volatile oil and TQ Urethane-anaesthetized rat Decreased arterial blood pressure and
heart rate in a dose-dependent manner 
Alpha-pinene Non-anaesthetized normotensive rat Hypotensive effect 
volatile of N. sativa,
α-pinene and p-cymene
Urethane-anaesthetized rat Reduced BP and heart rate 
TQ L-NAME-induced hypertension in rat
Reduced SBP in a dose dependent
manner, decreased creatinine and
increased GSH to normal levels
SOD: superoxide dismutase, TG: triglyceride, TC: total cholesterol, GSH/GSSG: glutathione/oxidized glutathione, SBP: systolic blood
pressure, RVH: renovascular hypertension, L-NAME: L-NG-nitroarginine methyl ester, BP: blood pressure, SBP: systolic blood pressure, DBP:
diastolic blood pressure, MAP: mean arterial pressure, LDL: low-density lipoprotein, TQ: thymoquinone, GSH: glutathione
Indian Journal of Pharmaceutical Sciences 975
signicantly increased left ventricular and whole heart
weights and enhanced levels of baseline peak tension,
maximum rate of tension development, heart rate and
myocardial ow rate.
The effect of oral administration
of N. sativa (800 mg/kg) for two months on cardiac
hemodynamics and adrenergic responsiveness also
showed that N. sativa resulted on intrinsic cardiac
contractile properties without evidence of increased
cardiac work load or energy consumption in vivo.
Furthermore, the supplementation of N. sativa for one
month on cardiac reserve in rats showed that N. sativa
developed a moderate but signicant hypertrophy that
was evident by an increase in the heart weight to body
weight ratio and associated with an increase in the
baseline cardiac inotropic properties.
Combination of N. sativa supplementation and
exercise training might induce a safer model of cardiac
hypertrophy. The effects of N. sativa (800 mg/kg) and
exercise (on treadmill, 2 h/day) on cardiac hypertrophy
in rats showed a synergistic effect of N. sativa treatment
with exercise training as N. sativa-exercise-induced
cardiac hypertrophy had lower heart rate and well-
matched electrical activity of the heart to its mass[58,59].
In a model of myocardial ischemic reperfusion injury
in rats, it was shown that oral administration of
N. sativa (800 mg/kg) increased contractile and vascular
functions and reduced oxidative stress in the cardiac
tissue. It also protected the heart against mitochondrial
permeability transition pore opening. The effect
of N. sativa (2 ml/kg, ip) on the heart rate, some
haematological values, and pancreatic β-cell damage
in cadmium-treated rats was showed that N. sativa
decreased the elevated heart rate, glucose concentration
and increased the lowered RBC and WBC counts as well
as hemoglobin (Hb) and packed cell volume values.
The results also suggest that the preventive effects of
N. sativa may be mediated by the inhibition of lipid
peroxidation and antioxidant property. Furthermore,
the effect of the plant (20 ml/kg) on heart rate in
alloxan-induced diabetic rabbits showed that N. sativa
treatment decreased the diabetes-induced disturbances
of heart rate and some haematological parameters of
alloxan-induced diabetic rabbits. In isoproterenol-
induced myocardial infarction, N. sativa seed extract
Plant preparation Study model Effect Reference
Essential oil of N. sativa Isolated vascular smooth muscles of rat Depressant effect on the frog heart
and a relaxant property 
Hydroethanolic extract Rat aortic smooth muscle contracted by
both KCl and phenylephrine The vasorelaxation effect 
TQ Smooth muscle of pulmonary artery
contracted by phenylephrine The relaxant effect 
TQ Endothelial dysfunction with ageing in rat
Improved endothelial function by
inhibition of oxidative stress and
normalization angiotensin system
N. sativa The intrinsic cardiac responses
Increased left ventricular and
whole heart weights, improved
baseline peak tension heart rate and
myocardial ow rate
N. sativa Cardiac reserve in rats
Increase heart weight to body weight
ratio and baseline cardiac inotropic
N. sativa N. sativa supplementation and exercise
training in rat
Cardiac hypertrophy, reduced heart
N. sativa Myocardial ischemic reperfusion injury in
Increased contractile and vascular
functions, reduced oxidative stress
in cardiac tissue
N. sativa Cadmium-treated rats
Decreased heart rate, glucose
concentration, increased RBC, WBC
counts, Hb, and PCV.
N. sativa Alloxan-induced diabetic rabbits Reduced heart rate 
N. sativa seed and oil
infarction in rats
Normalized altered levels of LDH,
CPK, AST, ALT and lipid prole 
Aqueous and macerated
extracts of N. sativa Isolated heart in guinea pig Inhibitory effect on heart rate and
heart contractility [31-32]
TABLE 2: THE EFFECT OF N. SATIVA AND ITS CONSTITUENTS ON VASCULAR SMOOTH MUSCLE,
ENDOTHELIAL DYSFUNCTION, HEART RATE AND HEART CONTRACTILITY
RBC: red blood cell, WBC: white blood cell, Hb: hemoglobin, PCV: packed cell volume, LDH: lactate dehydrogenase, CPK: creatine
phosphokinase,, AST: aspartate aminotransferase, ALT: alanine aminotransferase
Indian Journal of Pharmaceutical Sciences
(1000 mg/kg, po) and oil extract (2 ml/kg, po)
treatment for 21 d resulted in normalized levels of
LDH, CPK, AST, ALT, lipid prole. The effects of
N. sativa and its constituents on heart rate and heart
contractility were summarized in Table 2.
Effect on lipid prole:
The effect of methanolic extract (810 mg/kg) and
volatile oil (410 mg/kg) of N. sativa seed on
hyperlipidaemia rat showed that treatment with
the plant signicantly reduced the levels of plasma
triglycerides (TG), total cholesterol (TC), very
low density lipoproteins (VLDL-C), low density
lipoproteins (LDL-C), β-hydroxy β-methylglutaryl-
CoA reductase activity and increased high density
lipoproteins (HDL-C) concentration. Intra-gastric
gavage of petroleum ether extract of N. sativa seeds
reduced fasting plasma levels of insulin and TG and
increased HDL-C. Furthermore, oral administration
of N. sativa seed xed oil (1 ml/kg) in rats for 12 w
reduced TC, TG, glucose levels as well as leukocytes
and platelets counts and increased hematocrit and Hb
levels[60-66]. Treatment with N. sativa seed oil (800 mg/
kg, p.o. for 4 w) in rats was also signicantly decreased
serum TC, LDL, TG and increased serum HDL[61-67].
Treatment with N. sativa (50, 100, 200, 300, 400, 500
mg/day) also reduced serum TC, LDL, TG and increased
HDL/LDL ratio in normal rats. The inhibitory
effects of ethanolic extract of N. sativa seed (0.5, 1 and
1.5 mg/kg, ip) on adrenaline-induced dyslipidaemia
and left ventricular hypertrophy in rats was showed
that injection of the plant on adrenaline-induced
dyslipidaemia rats for two weeks signicantly reduced
TC, TG, LDL-C and increased HDL-C. However,
treatment with N. sativa for eight weeks increased
free radical scavenging activity and decreased the left
ventricular hypertrophy and cardiomyocyte size.
N. sativa (1000 mg/kg/day) in comparison to
simvastatin, a synthetic antihyperlipidemic drug in
Sprague Dawley rats showed signicant reduction
in TC, TG, LDL-C and increase of HDL-C. The
results suggested that N. sativa could be used as an
antihyperlipidemic drug without any side-effects[70,71].
Signicantly reduction of TC, TG, LDL-C, and MDA
has also been demonstrated as the effect of N. sativa
seed crushed treatment (7.5 g/kg/day) in a rabbit model
of hyperlipidemia. Furthermore, treatment with
N. sativa (5 %) signicantly reduced TC and LDL-C in
The effect of different extracts of N. sativa on lipid
prole in ovariectomized rats as an animal model of
menopause was evaluated and the results showed that
different extracts of N. sativa signicantly reduced
blood glucose and LDL-C, although the differences in
TC, TG and HDL-C were not signicant. Treatment
of either N. sativa (0.4 mg/kg) or olive oil (0.4 mg/kg) in
a mice model of hyperlipidaemia signicantly reduced
TC, TG, LDL-C and VLDL-C. However, the value of
HDL-C in olive oil group was signicantly higher than
in N. sativa group. The effect of acetone extracts of
N. sativa (0, 0.2, 0.4 % and N. sativa seed powder (0, 1.5,
2.5, 3.0 %) on hyperlipidaemia broiler chicks for 4 w
showed that supplementation of either the seed powder
or acetone extracts of the plant seeds signicantly
reduced TC and TG. The results of the effect of
N. sativa seed oil on lipid prole in sheep in contrast
to previous ndings showed that feeding with 4.7 %
of the plant oil in diets of sheep signicantly increased
TC, TG, LDL-C, and HDL-C. Supplementation of
N. sativa seed (2 %) also reduced HDL-C and elevated
TC, TG, LDL-C, VLDL-C in Pekin ducklings.
Canola oil and N. sativa seed powder signicantly
reduced TC and LDL-C but non-signicantly
increased HDL-C. Furthermore, treatment with N.
sativa (30 mg/kg, po) signicantly increased HDL-C
and decreased LDL-C. Palm oil increased the TC
and LDL-C; decreased HDL-C levels in albino rats at
24 w but treatment with N. sativa signicantly reduced
TC and LDL-C and increased HDL-C levels[82,83].
Supplementation with 5 % N. sativa signicantly
decreased arterial wall lipid deposition, TC and LDL
in hypercholesterolemia rabbits. TQ (10 mg/kg, po)
reduced TC, TG, and LDL-C and increased HDL-C
for a period of eight weeks in a rabbit model of
atherosclerosis although the differences in lipid prole
were not signicant[84,85]. Table 3 presented the effects
of N. sativa and its constituents on lipid prole.
Antiatherogenic and antiplatelet effects:
The effect of N. sativa seeds powder (1000 mg/kg) and
oil (500 mg/kg) in comparison to simvastatin (10 mg/kg)
on atherosclerosis in diet-induced hypercholesterolemia
rabbits for a period of eight weeks was investigated
and the results indicated that treatment with N. sativa
either powder or oil signicantly reduced arterial wall
lipid deposition, TC and LDL and increased HDL.
In addition, plaque formation signicantly inhibited
and reduced the intima/media ratio. The N. sativa
seeds powder (100 mg/kg/day) in diet-induced
Indian Journal of Pharmaceutical Sciences 977
hypercholesterolemia rabbits for a period of four weeks
was signicantly reduced serum levels of TC, TG, and
LDL-C and increased HDL-C. The methanol soluble
portion of the N. sativa seed oil showed inhibitory
effects on arachidonic acid (AA)-induced platelet
aggregation and blood coagulation. Some isolated
compounds from the oil such as 2-(2-methoxypropyl)-
5-methyl-1,4-benzenediol, thymol, carvacrol showed
signicantly higher effect on AA-induced platelet
aggregation and blood coagulation than aspirin. In
addition, fatty streak formation signicantly reduced
in the left and right coronary arteries and the aorta.
The results suggested that this effect of N. sativa may
be related to its antioxidant and antiinammatory
properties[88,89]. Treatment with propolis (a resinous
hive product collected by honeybees from various
plant sources) and TQ in hypercholesterolemia rabbits
also showed signicant reduction of serum TC,
LDL-C, triglycerides and thiobarbituric acid-reactive
concentrations, and increased HDL-C concentration,
as well as glutathione content. Histopathological
examination showed protective effect of propolis
and TQ against hypercholesterolemia-induced aortic
tissue damage. The results also suggested that the
protective effects of propolis and TQ maybe mediated
by antioxidant mechanism. Antiatherogenic and
antiplatelet effects of N. sativa and its constituents
have been shown in Table 4.
Effect on blood pressure:
Oral treatment of N. sativa seed in male patients with
mild hyperlipidaemia and hypertension for a period of
8 w demonstrated a signicant dose-dependent decline
in the levels of SBP and DBP. The antihypertensive
effect of N. sativa seed oil was evaluated on patients
with metabolic syndrome divided in two groups of
one, triple therapy including amlodipine 5 mg, atenolol
Plant preparation Study model Effect Reference
N. sativa Rat Increased HDL-C, decreased LDL-C 
N. sativa Rat feeded with palm oil Reduced TC and LDL-C, increased HDL-C [82,83]
N. sativa Rat feeded with cholesterol rich
diet Reduced TC, TG, LDL-C, increased HDL-C [70,71]
N. sativa Hyperlipidemia rabbit Reduced TC, TG, LDL-C, MDA 
N. sativa Hypercholesterolemia rabbit Reduced TC and LDL-C 
N. sativa Sunower oil, cholic acid and
propylthiouracil diet in rat Reduced TC, TG, LDL-C, increased HDL-C 
N. sativa Rat Reduced TC, LDL, TG, increased HDL/LDL
N. sativa and olive oil Hyperlipidemia mice Reduced TC, TG, LDL-C and VLDL-C,
increased HDL-C 
N. sativa seed Pekin ducklings Reduced HDL-C, elevated TC, TG, LDL-C,
N. sativa seed powder and
Canola oil Rat Reduced TC and LDL-C 
N. sativa seed xed oil Rat
Reduced TC, TG, glucose levels, leukocytes
and platelets counts, increased hematocrit
and hemoglobin levels
N. sativa oil Sheep Increased TC, TG, LDL-C, HDL-C 
N. sativa oil Rat Decrease TC, LDL, TG, increased HDL 
Methanolic extract and
volatile oil of N. sativa Hyperlipidemia rat Reduced TG, TC, VLDL-C, LDL-C, HMG-CoA
reductase activity, increased HDL-c 
Petroleum ether extract of
N. sativa seeds Rat Reduced fasting plasma levels of insulin and
TG, increased HDL-C 
Ethanolic extract of N.
and left ventricular hypertrophy
Reduced TC, TG , LDL-C, increased HDL-C 
methanol and hexane
extract of N. sativa
An animal model of menopause Reduced blood glucose and LDL-C 
Acetone extract and N.
sativa seed powder Hyperlipidemia broiler chicks Reduced TC and TG 
TABLE 3: THE EFFECT OF N. SATIVA AND ITS CONSTITUENTS ON LIPID PROFILE
TG: triglyceride, TC: total cholesterol, VLDL-C: very low density lipoprotein cholesterol, HDL-C: high density lipoprotein cholesterol, LDL-C:
low density lipoprotein cholesterol, MDA: malondialdehyde
Indian Journal of Pharmaceutical Sciences
50 mg and atorvastatin 10 mg once a day and the
second, triple therapy+a capsule containing 500 mg N.
sativa extract. Aspirin 150 mg was given in both groups
for a period of eight weeks. The ndings of this study
showed that N. sativa signicantly decreased SBP,
DBP and LDL-C and increased HDL. These ndings
suggest that N. sativa has signicant hypertensive
property and effect on dyslipidaemia. These results also
suggested that two possible mechanisms responsible
for antihypertensive effects of N. sativa are calcium
channel blocking and diuretic activity. The effect
of N. sativa seed oil on SBP and DBP in healthy
volunteers was also investigated. Each subject in the
N. sativa seed oil group received a bottle containing
150 ml N. sativa seed oil and in the placebo group
received a bottle containing 150 ml mineral oil every 4
w during the 8 w trial. The results indicated that N. sativa
signicantly decreased SBP and DBP. Combination
therapy of N. sativa seeds (50 mg/kg b.w) and honey
mixture also signicantly reduced SBP and DBP.
The clinical effects of N. sativa and its constituents on
blood pressure are summarized in Table 4.
Effect on lipid prole:
In a clinical study, the effects of N. sativa seed powder
on serum cholesterol, HDL and LDL-c and TG in
menopausal women of 2 groups including: treatment
group received N. sativa powder (500 mg) capsules and
placebo group received the placebo capsules (wheat
germ, 100 mg) was investigated. Capsules of N. sativa
powder were orally administered at a dose of 1 g after
breakfast every day for a period of two months. The
results indicated that N. sativa signicantly increased
serum HDL-C and decreased LDL-C, TC, TG and FBG.
However, the differences in BP were not signicant
between the treatment and placebo over the period of
intervention. Treatment with N. sativa seed oil also
signicantly increased serum HDL-C and decreased
LDL-C in patients with metabolic syndrome. The oral
treatment of N. sativa powder in hypercholesterolemia
patients at the dose of 1 g daily before breakfast for
two months signicantly reduced serum levels of TC,
LDL and TG, and increase HDL. In addition, serum
TC, LDL and TG were reduced signicantly after
6 mo of treatment with N. sativa powder (500 mg)
and statin (10-20 mg) in patients with stable coronary
artery disease in Multan, Pakistan compared to group
receiving statin (10-20 mg) alone. The effect of oral
treatment of N. sativa seed in male patients with mild
dyslipidaemia and hypertension was also investigated
for a period of eight weeks. Patients were randomized
into three groups: a placebo and two test groups that
received 100 and 200 mg of N. sativa extract twice a
day. The results showed a signicant dose-dependent
decline in the serum levels of TC, TG, LDL, SBP, and
DBP in N. sativa extract groups.
The effect of N. sativa on the blood levels of glucose,
uric acid, TG, cholesterol, blood urea nitrogen (BUN)
and creatinine in normal healthy human subjects
was evaluated in two groups, I) test group received
N. sativa powder (500 mg) capsules, II) the placebo
group received the placebo capsules (brown sugar,
Plant preparation Study model Effect Reference
N. sativa Hypercholesterolemia rabbit Decreased TC, LDL-C and fatty streak
N. sativa seeds powder Hypercholesterolemia rabbit Reduced TC, TG, LDL-C, increased HDL-C 
N. sativa seeds powder
and oil Hypercholesterolemia rabbit
Reduced arterial wall lipid deposition, TC,
LDL, plaque formation and the intima:
media ratio, increased HDL
Methanol soluble portion
of the N. sativa seed oil
Arachidonic acid (AA)-induced
platelet aggregation and blood
Inhibitory effect on platelet aggregation and
blood coagulation 
TQ and propolis Hypercholesterolemia rabbit
Reduced TC, LDL-C, TG and thiobarbituric
acid-reactive substances, increased HDL-C
and glutathione content
N. sativa seed Patients with mild hyperlipidemia
and hypertension Dose-dependent decline in SBP and DBP 
N. sativa oil Patients with metabolic syndrome Decreased SBP, DBP 
N. sativa oil Normal healthy human Decreased SBP and DBP 
N. sativa seeds and honey
mixture Hypercholesterolemia patients Decreased SBP, DBP 
TABLE 4: ANTIATHEROGENIC, ANTIPLATELET AND BLOOD PRESSURE-LOWERING EFFECTS OF N.
SATIVA AND ITS CONSTITUENTS
TG: triglyceride, TC: total cholesterol, HDL-C: high density lipoprotein cholesterol, LDL-C: low density lipoprotein cholesterol, TQ:
thymoquinone, SBP: systolic blood pressure, DBP: diastolic blood pressure
Indian Journal of Pharmaceutical Sciences 979
500 mg) twice daily. The results indicated that
N. sativa signicantly reduced blood levels of glucose
and cholesterol. Favourable effects of the capsulated
N. sativa powder (500 mg) on blood pressure, serum
total cholesterol, LDL cholesterol, triglycerides, and
fasting blood sugar have also been reported in another
human study but results were not statistically signicant
because of small sample size. The effects N. sativa
supplementation (2 g/day) and aerobic training on lipid
prole in sedentary overweight females for a period
of eight weeks also indicated that the combination
of the plant and aerobic exercise caused signicant
improvements in serum LDL-C and HDL-C. In
addition, administration of 200 mg N. sativa seed twice
daily for three months in patients with ischemic heart
disease also signicantly reduced TG and increased
The effect of 2.5 ml N. sativa seed oil twice daily
in comparison to atorvastatin 10 mg once a day,
metformin 500 mg twice a day, atenolol 50 mg once
a day, amlodipine 5 mg once a day for a period of six
weeks in patients with metabolic syndrome showed
that treatment with N. sativa signicantly decreased
serum levels of LDL-C and increased HDL-C. The
supplementation of 2.5 ml N. sativa seed oil twice a
day for a period of eight weeks signicantly reduced
fasting blood cholesterol, LDL, TG, glucose and
HbA1C levels in healthy subjects. Furthermore,
administration of 3 g/day N. sativa seed oil for two
months signicantly reduced TG, VLDL, weight and
waist circumference in obese women.
Treatment with N. sativa 2 g/day for 4 w in
hyperlipidemia patients showed signicant decrease
in serum levels of TC, TG and LDL. Saboos-
e-Asapghol (Plantago ovata) 4 g and N. sativa
2 g twice daily for a period of 90 d in patients with
hypertriglyceridemia also signicantly reduced serum
TG level. The effect of N. sativa seed oil (100,
140 ng/ml) on regulation of primary human monocyte
growth and CD11b expression showed that N. sativa
Plant preparation Study model Effect Reference
N. sativa Hyperlipidemia patients Decreased TC, TG and LDL 
N. sativa Hyperlipidemia patients Reduced LDL-C, increased HDL-C 
N. sativa Normal healthy human Reduced blood levels of both glucose and
N. sativa seed powder Menopausal women Increased HDL-C, decreased LDL-C, TC, TG and
N. sativa powder Hypercholesterolemia patients Reduced TC, LDL and TG, increased HDL 
N. sativa powder Patients with stable coronary
Reduced TC, LDL and TG
N. sativa seed Patients with mild
hyperlipidemia and hypertension
Signicant dose-dependent decline in the
levels of TC, TG ,LDL 
N. sativa seed Patients with ischemic heart
N. sativa seed Hyperlipidemia patients Reduced TC, TG, LDL-C, increased HDL-C 
N. sativa seed oil Normal healthy human Reduced fasting blood cholesterol, LDL, TG,
glucose and HbA1C levels 
N. sativa seed oil Obese women Reduced TG, VLDL, weight and waist
N. sativa oil Patients with metabolic
syndrome Decreased LDL-C, increased HDL-C 
N. sativa oil Patients with metabolic
syndrome Decreased LDL-C, increased HDL 
N. sativa seeds and honey
mixture Hypercholesterolemia patients Decreased TC, TG, TC:HDL-c, increased HDL-c 
N. sativa seeds, garlic oil
and simvastatin Patients with dyslipidemia Reduced TC, TG, LDL-C, Non-HDL, increased
N. sativa and aerobic
exercise Sedentary overweight females Improved LDL‑C and HDL-C 
N. sativa and Saboos-e-
Asapghol Hypertriglyceridemia patients Reduced TG 
TABLE 5: CLINICAL EFFECTS OF N. SATIVA AND ITS CONSTITUENTS ON LIPID PROFILE
TG: triglyceride, TC: total cholesterol, VLDL: very low-density lipoprotein, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density
lipoprotein cholesterol, FBG: fasting blood glucose, HbA1C: hemoglobin A1C
Indian Journal of Pharmaceutical Sciences
seed oil provided preliminary support on regulation
of cell growth and differentiation in monocyte and
monocyte-derived macrophages and reduced CD11b
expression. Two tea spoons (approximately 9.0 g)/
day N. sativa seed compared to gembrozil 600 mg
twice daily for a period of eight weeks in hyperlipidemia
patients signicantly reduced serum levels of TC, TG,
and LDL-C and increased HDL-C.
The effects of N. sativa in comparison to nicotinic
acid along with low fat diet and physical exercise
in hyperlipidemia patients divided to three groups:
I) placebo group, II) 2 tea spoons N. sativa after
breakfast, and III) niacin 2 g in divided doses, after
breakfast, lunch and dinner for the period of two months
was investigated. The results showed that N. sativa and
niacin signicantly reduced serum level of LDL-C and
increased HDL-C in hyperlipidemia patients.
Combination therapy of N. sativa seeds (50 mg/kg)
and honey signicantly decreased serum TC, TG, TC:
HDL-C, as well as SBP, DBP and increased HDL-C
in hypercholesterolemia. Combination treatment
of N. sativa seeds (500 mg), garlic oil (250 mg) and
simvastatin (10 mg) capsule once daily after meal at
night signicantly reduced serum TC, TG, LDL-C,
and Non-HDL and elevated HDL-C in dyslipidemia
patients. The effects of N. sativa and its constituents
on lipid prole in human studies were shown in
From various reports, it is concluded that N. sativa and
its main constituent's, TQ showed antihypertensive,
antiatherogenic, antihyperlipidemic, hypoglycemic
and cardioprotective effects. The results of reviewed
articles indicated the preventive and therapeutic effects
of N. sativa and its constituents on cardiovascular
diseases. However, further investigations are required
to reveal the exact perspectives of molecular and
cellular basis of N. sativa and its constituent’s effects
on cardiovascular disorders. In addition further
clinical investigations also needed to be conducted
regarding the effect of the plant and its constituents on
Conﬂicts of interest:
There are no conicts of interest among the authors.
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