ArticlePDF AvailableLiterature Review

Abstract and Figures

Objectives Nigella sativa (black seed or black cumin), which belongs to the Ranunculacea family, is an annual herb with many pharmacological properties. Among its many active constituents, thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa (N. sativa) seeds, and it is the constituent to which most properties of this herb are attributed. Methods PubMed-Medline, Scopus, and Web of Science databases were searched to identify randomized control trials (RCTs) investigating the therapeutic effects of N. sativa and/or TQ. In this review, we investigated the clinical uses of N. sativa and TQ in the prevention and the treatment of different diseases and morbidity conditions in humans. Results Black seed and TQ are shown to possess multiple useful effects for the treatment of patients with several diseases, such as inflammatory and auto-immune disorders, as well as metabolic syndrome. Also, other advantages, including antimicrobial, anti-nociceptive and anti-epileptic properties, have been documented. The side effects of this herbal medicine appear not to be serious, so it can be applied in clinical trials because of its many advantages. Conclusion Some effects of N. sativa, such as its hypoglycemic, hypolipidemic and bronchodilatory effects, have been sufficiently studied and are sufficiently understood to allow for the next phase of clinical trials or drug developments. However, most of its other effects and applications require further clinical and animal studies.
Content may be subject to copyright.
Review on Clinical Trials of Black Seed (
Nigella sativa
and Its Active Constituent, Thymoquinone
Alireza Tavakkoli1, Vahid Mahdian2, Bibi Marjan Razavi3 and Hossein Hosseinzadeh4,*
Objectives: Nigella sativa (black seed or black cumin),
which belongs to the Ranunculacea family, is an annual
herb with many pharmacological properties. Among
its many active constituents, thymoquinone (TQ) is
the most abundant constituent of the volatile oil of Ni-
gella sativa (N. sativa) seeds, and it is the constituent to
which most properties of this herb are attributed.
Methods: PubMed-Medline, Scopus, and Web of Sci-
ence databases were searched to identify randomized
control trials (RCTs) investigating the therapeutic eects
of N. sativa and/or TQ. In this review, we investigated
the clinical uses of N. sativa and TQ in the prevention
and the treatment of dierent diseases and morbidity
conditions in humans.
Results: Black seed and TQ are shown to possess multi-
ple useful eects for the treatment of patients with sev-
eral diseases, such as inammatory and auto-immune
disorders, as well as metabolic syndrome. Also, other
advantages, including antimicrobial, anti-nociceptive
and anti-epileptic properties, have been documented.
e side eects of this herbal medicine appear not to be
serious, so it can be applied in clinical trials because of
its many advantages.
Conclusion: Some eects of N. sativa, such as its
hypoglycemic, hypolipidemic and bronchodilatory
eects, have been suciently studied and are su-
ciently understood to allow for the next phase of clini-
cal trials or drug developments. However, most of its
other eects and applications require further clinical
and animal studies.
1. Introduction
Nigella sativa (black seed or black cumin), which be-
longs to the Ranunculacea family, is an annual herb
with many pharmacological properties [1]. e use of
N. sativa (NS) seeds and oil in traditional remedies goes
back more than 2000 years, and the herb is described
as ‘the Melanthion’ by Hippocrates and Discroides [2].
Black seeds and their oil have a long history of folklore
usage in the Indian and the Arabian civilizations as
food and medicine and have been commonly used as
treatment for a variety of health conditions pertaining
to the respiratory system, digestive tract, kidney and
liver functions, cardiovascular system, and immune
system support, as well as for general well-being [3, 4].
NS contains many active components, such as thymo-
quinone (TQ), alkaloids (nigellicines and nigelledine),
saponins (alpha-hederin), avonoids, proteins, fatty
acids, and many others, that have positive eects in
the treatment of patients with dierent diseases [5, 6].
TQ is the most abundant constituent in the volatile oil
of NS seeds, and most of the herb’s properties are at-
tributed to it.
Cell culture studies and animal models have indicat-
Review article
Key Words
black seed, clinical trials, diseases, Nigella sativa, safety,
ISSN 2093-6966 [Print], ISSN 2234-6856 [Online]
Journal of Pharmacopuncture 2017;20[2]:107-111
This is an Open-Access article distributed under the terms of the Creative Commons
Attribution Non-Commercial License (
which permits unrestricted noncommercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.
This paper meets the requirements of KS X ISO 9706, ISO 9706-1994 and ANSI/NISO
Z39.48-1992 (Permanence of Paper).
*Corresponding Author
Hossein Hosseinzadeh. Pharmaceutical Research Center, Department of Pharmacody-
namics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences,
Mashhad, Iran.
Tel: +98-51-1881-9042 Fax: +98-51-1882-3251
2017 Korean Pharmacopuncture Institute
Received: Apr 28, 2017 Reviewed: Aug 21, 2017 Accepted: Aug 30, 2017
1 
3 
ed several therapeutic potentials, such as anti-cancer [5,
7-9], antimicrobial [10, 11], analgesic [12, 13], antipyretic
[14], contraceptive and anti-fertility, anti-oxytocic [3], anti-
tussive [15], anti-inammatory [12, 16], and anti-oxidant
[17-19] potentials, for black seed and its active component
TQ. NS or TQ anticancer activity has been demonstrated
for blood, breast, colon, pancreatic, liver, lung, brosar-
coma, prostate, and cervix cancer cell lines and in animal
models of lung, kidney, skin, colon, and breast cancer [7].
Black seed’s antimicrobial eects include those on gram-
negative and gram-positive bacteria, viruses, parasites,
Schistosoma, and fungi pathogens [10]. NS was also found
to be able to relieve the symptoms of or cure patients with
several diseases, such as hypertension, dyslipidemia, met-
abolic syndrome, diabetes [5, 20, 21], asthma [3], convul-
sion [22-24], and natural and chemical toxicities [25, 26].
Additionally, a suggestion was made that NS and TQ uti-
lization could prevent many disorders [6], including neu-
robehavioral [27], kidney [28, 29], and liver [4] disorders.
For these reasons, in this review, we investigated the clini-
cal uses of NS and TQ in the prevention and treatment of
dierent diseases and morbidity conditions in humans.
2. Methods
PubMed-Medline, Scopus, and Web of Science databases
were searched to identify randomized control trials (RCTs)
investigating the therapeutic eects of NS and/or TQ. We
reviewed the existing literature published until April 2016
by using the following keywords: "Nigella sativa'', "black
cumin'', "black seeds'', "thymoquinone'', and "patient'',
"clinic'' or "clinical trial''. All studies assessing the eects
of NS or TQ, topical use or oral intake, on human health
conditions were included.
3. Results
3.1. Safety
Administration of NS oil (5 mL/day) to healthy volunteers
for 8 weeks was reported not to have any notable liver,
kidney, or gastrointestinal side eects [30, 31]. NS oil in-
take (equivalent to oil obtained from 0.7 g of seeds) for 40
days showed reasonable kidney and liver safety in patients
with type 2 diabetes mellitus (DM); neither did it alter the
platelet or the total leukocyte count [32]. Another study
performed on 39 centrally obese men demonstrated that
intake of NS seeds (3 g/day for 3 months) had no detect-
able side eects [33]. Qidwai et al reported that the admin-
istration of NS seeds (2 g/day for 6 weeks) did not aect the
serum alanine aminotransferase (ALT) or the serum creat-
inine (Cr) levels in adults [34]. Furthermore, NS at doses of
1, 2 and 3 g/day for 3 months did not adversely aect either
the renal or the hepatic functions of diabetic patients [35].
Another study revealed that NS seed powder intake for 40
days caused no signicant change in total leukocyte and
platelet count [36].
Treatment with NS tea (5 g/day) added to the usual oral
anti-diabetic drugs, diet, and exercise for 6 months showed
signicant decreases in aspartate aminotransferase (AST),
ALT, serum total, direct and indirect bilirubin, serum Cr,
and blood urea levels in type 2 diabetic patients, as well as
improved liver and kidney functions [37]. e intake of NS
extract (200 or 400 mg/day) for 2 months was also reported
to cause no observable complications in patients with mild
hypertension [38].
No adverse eects were reported in applications of NS
oil twice daily for six months to the lesions of vitiligo pa-
tients [39]. Intake of NS oil (0.05 mL/kg/day) in osteopenic
postmenopausal women for three months showed no
benecial eects; however, no adverse side eects were
produced, either [40]. In another study conducted on Ira-
nian infertile men in order to assess the impacts of NS oil
(5 mL/day) on abnormal semen quality, no side eects
were observed [41]. Whereas no severe side eects were
reported in administration of NS oil (5 mL/day) to func-
tional dyspeptic patients, some mild adverse impacts were
observed, including nausea, bloating, and burning sensa-
tion [42]. On the other hand, some cases of epigastric pain
and hypoglycemia were reported as adverse eects when
NS oil capsules were used to treat patients with hepatitis
C virus (HCV) [43]. Dirjomuljono et al demonstrated the
safety of NS extract (1,080 mg/day) when used to treat pa-
tients with acute tonsillopharyngitis [44]. In another study
that investigated the anti-cestodal eects of NS powdered
seeds (40 mg/kg body weight) on children infected with
cestodes, no serious side eects were reported [45].
Treatment of seasonal allergic rhinitis patients with NS
seeds (250 mg/day) for two weeks has been reported not
to cause any adverse eects [46]. However, some patients
with allergic rhinitis when treated using nasal drops of
NS oil showed nasal dryness [47]. Dogar et al conrmed
that side eects produced by treatment of children with
acute lymphoblastic leukemia (ALL), aged between 2 - 18
years, with NS powder (40 mg/kg in two equal doses for 3
months), along with conventional therapy, were remark-
ably less than they were for L-asparaginase and conven-
tional therapy (note: conventional therapy includes dau-
norubicin, vincristine, and prednisolone). us, one can
conclude that NS powder, as an anti-cancer agent, is a
benecial substitute for L-asparaginase in the treatment of
patients with ALL [48].
Nevertheless, in a patient suering from DM, along with
coronary artery disease and hypertension, acute renal fail-
ure due to the use of NS tablets (2,000 – 2,500 mg/day) was
reported to have occurred 6 days after the start of treat-
ment [49]. Bamosa suggested that this adverse eect could
not have been related to NS because other clinical trials
with many more human subjects had demonstrated the
safety of NS in higher doses over longer periods of intake
and that the adverse eect could probably be attributed
to contamination of the tablets with other products [50].
Ibraheim also reported that only the total oil showed sig-
nicant increases in the AST and the ALT levels while both
the oil and the crushed seeds showed signicant increases
in the
-GT and the alkaline phosphatase (ALP) activities
[51]. A case of systemic and contact bullous drug eruption
as erythematous plaques with vesicles and bullous lesions
because of topical application and digestion of NS oil was
Journal of Pharmacopuncture 2017;20(2):107-111 109
Journal of Pharmacopuncture 2017;20(2):107-111
Study design Population
Part of the herb, dose,
and duration of treat-
Result References
72 Type 2 DM patients
(men and women aged
30 - 60 years old)
NS oil (3 g/day)
12 weeks
BMI, insulin level and insulin
resistance as well as HDL-C as
compared with baseline ,
FBS, TG, LDL-C and HbA1c as
compared to the placebo group
41 Type 2 DM patients
(men and women aged
30 - 60 years old)
NS oil (equivalent to
oil obtained from 0.7 g
of seeds)
40 days
FBS , insulin, but reversed
after 40 days of placebo adminis-
Prospective study
60 patients with insulin
resistance (men and
NS oil (5 mL/day) +
atorvastatin (10 mg/
day) and metformin
(1 g/day)
6 weeks
TC, LDL-C and FBS [78]
double blind,
clinical trial
43 Type 2 DM patients
(men and women)
NS oil extract
(1 g/day)
8 weeks
TG, LDL-C, TC, and LDL-C to
HDL-C ratios as compared to the
-41 type 2 DM patients
(men and women)
NS tea (5 g/day) +
usual oral anti-dia-
betic drugs, diet, and
6 months
FBG, PPBG and HbA1c [37]
-94 type 2 DM patients
(men and women)
NS seeds 2 g/day or 3
12 weeks
FBG, 2hPG, and HbA1c,
Insulin resistance ,
-cell function; no signicant
change in body weight
NS seeds 1 g/day,
12 weeks insignicant changes [35]
41 type 2 DM patients
(men and women aged
30 - 60 years old)
NS seed powder,
40 days
FBG, TC, LDL-C and TG,
HDL-C and insulin; all men-
tioned values except HDL signi-
cantly reversed again after 40 days
of placebo intake
Table 1 Eects of Nigella sativa supplementation on patients with diabetes
DM, Diabetes mellitus; NS, Nigella sativa; BMI, Body mass index; HDL-C, High density lipoprotein-cholesterol; TG, Triglyceride; LDL-
C, Low density lipoprotein-cholesterol; HbA1c, Haemoglobin A1c; FBS, Fasting blood sugar; TC, Total cholesterol; FBG, Fasting blood
glucose; PPBG, Postprandial blood glucose; 2hPG, 2 hours postprandial glucose.
reported [52]. In addition, another report showed that the
use of NS at 5 g/day inhibited CYP2D6- and CYP3A4-me-
diated metabolism of dextromethorphan in healthy hu-
man volunteers, showing that it may interact with other
CYP2D6 and CYP3A4 substrates [53].
Taken together, NS has been established as a safe herbal
product. Nevertheless, according to the mentioned stud-
ies, some adverse eects, including nausea, bloating, and
burning sensation, have been reported after administra-
tion of NS oil in functional dyspeptic patients, and a slight
increase in liver and kidney enzymatic markers has been
shown following consumption of NS oil and crushed seeds.
3.2. Metabolic syndrome
Metabolic syndrome is a cluster of cardio-metabolic
conditions that include obesity, insulin resistance, ather-
ogenic dyslipidemia, and high blood pressure (BP) [54]
and is a major contributor to the development of diabetes
[55]. A RCT done on 60 patients with metabolic syndrome
showed that NS oil (5 mL/day) used in combination with
atorvastatin and metformin could decrease fasting blood
sugar (FBS), LDL, and TC signicantly after six weeks
of use, but had no signicant eect on body mass index
(BMI) or waist circumference (WC) [56].
Another study by Amin et al evaluated the eect of black
seeds (1.5 g/day) alone and concurrent with turmeric
(900 mg and 1.5 g/day, respectively) on 250 patients with
metabolic syndrome. e results show that NS and tur-
meric alone improved BMI, WC and BF% after 4 weeks,
compared to baseline. Combination therapy improved
all parameters including BMI, BF%, WC, hip circumfer-
ence (HC), BP, total cholesterol (TC), triglyceride (TG),
and C-reactive protein (CRP) except HDL-cholesterol with
lower FBG and LDL-cholesterol as compared to placebo
after four weeks. After 8 weeks, NS reduced lipids and FBG,
whereas turmeric decreased LDL-cholesterol and CRP.
Combination therapy showed an improvement in all pa-
rameters and reduced BF%, FBG, cholesterol, TG, LDL-
cholesterol, CRP and increased HDL-cholesterol [57].
In another study, premenopausal women underwent the
following protocol: 12-week administration of NS-powder
capsules (1,600 mg/day), a 2-week washout period, and
12-week administration of a placebo, and vise versa. e
authors of the study concluded that NS could help to con-
trol weight gain, the lipid prole, and the blood glucose
and hormonal levels [58]. According to a clinical trial by
Najmi et al, NS (500 mg/day) after 8 weeks was able to im-
prove the ecacy of the therapeutic protocol (metformin
+ atorvastatin + aspirin) in patients with metabolic syn-
drome and poor glycemic control so that NS-treated pa-
tients indicated signicant improvements in their FBG,
postprandial blood glucose (PPBG), haemoglobin A1c
(HbA1c), and LDL-C levels [59].
e eects of NS and TQ on dierent components of met-
Journal of Pharmacopuncture 2017;20(2):107-111
Table 2 Clinical eects of Nigella sativa supplementation on the nervous system
NS, Nigella sativa.
Study design Population
Part of the herb, dose,
and duration of treat-
Result References
crossover clinical trial 23 epileptic children
Water extract of black
seed (40 mg/kg/8 h),
10 weeks
Signicant reduction of
mean frequency of seizures [80]
Pilot, double-blinded
crossover clinical trial 22 epileptic children ymoquinone
(1 mg/kg), 10 weeks
Signicant reduction of
frequency of seizures [81]
crossover pilot study
30 intractable
epileptic patients
40 - 80 mg/kg/day of
black seed oil,
10 weeks
No benecial eects in the
frequency and
severity of seizures
clinical trial
40 healthy
elderly volunteers
500 mg NS seed cap-
sule twice a day,
9 weeks
Improvement of cognition,
memory, and attention [83]
clinical trial
48 healthy
adolescent males
500 mg NS capsule
once daily, 4 weeks
Enhancements of mood,
anxiety, and cognition [84]
- 35 male opiate addicts 500 mg NS daily,
12 weeks
Signicant reduction of
withdrawal eects [85]
Randomized, triple-
blind, active, and
clinical trial
52 women with cyclic
Topical 600 mg
NS oil twice a day,
2 months
Signicant improvement of
the pain scores [86] 111
Journal of Pharmacopuncture 2017;20(2):107-111
abolic syndrome and cardiovascular disease risk factors,
including high BP, obesity, dyslipidemia, and high blood
glucose, have been established [21]. e clinical uses of NS
and TQ in the prevention and treatment of these factors
will be discussed in subsequent subsections.
3.3. Hypertension
Hypertension (HT) is a lifestyle-related disease, and di-
etary modications are eective for its management and
prevention. In a study performed by Dehkordi and Kam-
khah, which evaluated the anti-hypertensive eect of NS,
the intake of NS extract (200 or 400 mg/day) for 2 months
was reported to decrease both the systolic and the diastolic
BP in patients with mild HT as compared with the baseline
and the placebo values [38]. Another study by Huseini et al
on healthy volunteers who received NS oil (5 mL/day) for
two months revealed the hypotensive eect of NS, with the
systolic and the diastolic BP being lowered signicantly as
compared with both the placebo and the baseline values
3.4. Obesity
Obesity, dened as excess fat mass, increases the risks for
multiple metabolic diseases, such as type 2 diabetes, car-
diovascular disease, and several types of cancer [60]. Some
RCTs demonstrated that NS oil in combination with a low-
calorie diet decreased weight in obese women in compari-
son to the placebo level [61, 62]. It also caused the super-
oxide dismutase (SOD) level to be elevated [61] and the TG
and the LDL-C levels to be decreased [62].
Another study was performed on 39 centrally obese men
to evaluate the eect of NS on body weight, WC, and some
biochemical parameters [33]. e results of that study
showed that intake of NS seeds (3 g/day for 3 months)
caused a very signicant reduction in body weight and
WC, but insignicant reductions in the serum free testo-
sterone level, as well as the systolic and the diastolic BP,
and an insignicant increase in the adiponectin level. e
reduction of serum free testosterone in the control group,
who received two capsules of 750 mg our twice daily, was
more than it was in the treatment group, thus indicating
that NS can inhibit the decrease in the serum free testo-
sterone level.
3.5. Dyslipidemia
Dyslipidemia is dened as the derangements of one or
more of the lipoproteins in blood, such as elevated TC,
LDL-C, and/or TG, or low levels of HDL-C alone [63].
Moeen-ud-din et al reported that the intake of 2 teaspoons
of NS seeds for 6 weeks by hyperlipidemic patients de-
creased their LDL-C (P-value < 0.001) and increased their
HDL-C (P-value < 0.01) as signicantly as niacin [64]. e
results of another RCT indicated that compared to mineral
oil, administration of NS oil (5 mL/day) to healthy volun-
teers for 8 weeks induced signicant decreases in the fast-
ing blood cholesterol, LDL, TG, glucose, and HbA1C levels
[30]. Administration of NS seeds (two spoons/day) to male
and female hyperlipidemic patients for 4 weeks signi-
cantly (P-value < 0.001) increased HDL-C and decreased
body weight [65].
Menopausal women are one of the high risk groups for
developing dyslipidemia. In a study by Ibrahim et al, the
administration of powdered NS seeds (1 g/day) over a two-
month intervention was found to decrease signicantly
the TG, LDL-C and TC levels, but to increase the HDL-C
level [66]. However, one month after cessation of treat-
ment, the lipid proles in the NS-treated group tended to
change towards the pretreatment levels. Another clinical
trial done for a similar duration showed that a supplement
of powdered NS seeds (1 g/day) could improve some bio-
chemical parameters, including the lipid prole and blood
glucose, in menopausal women, but had no signicant ef-
fect on their body weight [67].
According to a World Health Organization (WHO) report,
coronary heart disease is a major cause of mortality in the
world [68]. e results of a study which examined the ef-
fects of NS on the lipid proles in patients with stable coro-
nary artery disease indicated that intake of NS powder (500
mg/day) for 6 months concurrent with statin (10 - 20 mg/
day) both decreased the serum levels of TG, VLDL, LDL,
and TC and elevated the HDL level signicantly whereas
statin alone decreased neither the TG, VLDL, LDL nor TC
level [69].
In healthy female volunteers, administration of both
crushed seeds and the formulated total oil of NS caused
signicant reductions in the prolactin, glucose, triglycer-
ide, and cholesterol levels. Additionally, administration
of the crushed seeds caused a signicant increase in the
white blood cell count (WBC) and the hemoglobin level
whereas administration of NS oil only increased the hemo-
globin level signicantly [51]. In another study, Bamosa et
al suggested that the administration of NS at 2 g/day for 2
weeks decreased the blood levels of both glucose and cho-
lesterol in healthy volunteers [70].
A large RCT compared the eects of simvastatin (10 mg/
day) alone and concurrent with NS seeds (500 mg/day) and
garlic oil (0.625 mg/day) on the lipid prole in 258 patients
with hyperlipidemia over an 8-week treatment [71]. In that
study, a comparison of mean values between the two treat-
ment groups indicated a highly signicant dierence (P =
< 0.01) for cholesterol, TG, non-HDL, and LDL reductions
and a signicant dierence (P = 0.03) for HDL elevation
[71]. Sabzghabaee et al reported that the TC, LDL, and TG
serum levels in hypercholesterolemic patients who took
NS at 2 g/day for 4 weeks decreased signicantly [72]. e
uses of NS extract at 200 and 400 mg/day for 2 months were
also reported to have decreased both the total and the LDL
cholesterol in patients with mild HT as compared with the
baseline [38].
Of course, some controversies exist in the clinical trial
results. Qidwai et al reported that NS seeds (2 g/day) ad-
ministration had not aected the BMI, waist-hip ratio, BP,
FBS or serum lipids in adults after 6 weeks of use [34]. Un-
like pervasive evidence for the eects of NS use on the lipid
prole, the administration of powdered NS seeds was re-
Figure 1 Schematic description for the eects of Nigella sativa in dierent parts of the human body
ported to have had no signicant eect on BP, serum lipid
levels, blood sugar, or body weight in adults [73]. According
to some meta-analyses, overall, the use of NS was shown
to reduce the plasma levels of TC, LDL-C and TG, but its
eect on HDL-C was not signicant [74, 75]. Whereas the
use of NS seed oil was observed to have greater eects on
the serum TC and the LDL-C levels, versus the use of seed
powder, elevation of the HDL-C levels was found only after
supplementation with NS seed powder [75].
3.6. Diabetes
DM is characterized by chronic elevation of blood glu-
cose, which is a central factor in the production of reactive
oxygen species (ROS) that, in turn, promote cellular dam-
age and contribute to the development and progression
of diabetic complications [76]. In a report by Heshmati et
al, although the administration of NS oil at 3 g/day for 12
weeks was stated to have caused insignicant decreases in
the BMI, insulin level, and insulin resistance, as well as an
increase in the HDL-C level, in patients with type 2 diabe-
tes, the FBS, TG, LDL-C, and HbA1c levels were observed
to have been lowered signicantly in the intervention
group as compared to the placebo group [77].
Another clinical trial showed that NS oil intake (equiva-
lent to oil obtained from 0.7 g of seeds) for 40 days caused a
signicant reduction of FBS and a signicant rise of insulin 113
Table 3 Eects of Nigella sativa supplementation on patients with some diseases of the respiratory system
NS, Nigella sativa.
Disease Study design Population
Part of the herb,
dose, and duration
of treatment
Result References
-15 asthmatic
NS boiled extract
(50 and 100 mg/kg )
NS was less eective than
theophylline and salb-
utamol, on pulmonary
function tests
clinical trial
29 asthmatic
15 mL/kg/day of
0.1% NS boiled
extract, 3 months
Prophylactic eects of NS
on asthmatic patients [97]
open study
84 patients of
wheeze associated
NS oil (0.1 mg/kg),
14 days
More benecial eects in
reducing the pulmonary
index and improving the
peak expiratory ow rate
controlled trial
40 chemical war
0.375 mL/kg/day of
50g NS boiled water
2 months
Prophylactic eect of NS
on chemical war victims [99]
clinical trial
47 untreated adult
patients with
seasonal allergic
NS seeds
(250 mg/day),
2 weeks
Decreasing daytime, oph-
thalmic, and nighttime
clinical trial
68 patients with
allergic rhinitis
Nasal drops of NS
oil (each drop: 15
mL oil), 6 weeks
Notable symptomatic
improvement of patients [47]
parallel, randomized,
186 acute tonsil-
NSPN capsule
( 360 mg NS and
50 mg Phyllanthus
niruri extracts),
thrice/day, 7 days
Treatment of the symp-
toms of the disease [44]
in type 2 DM patients [32]. In still another study, the ad-
dition of NS oil at 5 mL/day to atorvastatin at 10 mg/day
and metformin at 1 g/day was shown to have induced sig-
nicant reductions in the TC, LDL-C, and FBS levels after
6 weeks of use in patients with insulin resistance [78]. Fur-
thermore, according to a study performed by Hadi et al on
43 type 2 diabetic patients, after an 8-week treatment, the
administration of NS oil extract at 1 g/day decreased the
serum levels of TG, LDL-C, and TC, as well as the LDL-C
to HDL-C ratio, signicantly in comparison to the placebo
[79]. Moreover, treatment with NS tea at 5 g/day added to
the usual oral anti-diabetic drugs, diet, and exercise for 6
months led to signicant decreases in the FBG, PPBG, and
HbA1c level in type 2 diabetic patients [37]. Another clini-
cal trial showed that the administration of NS at a dose of
2 g/day over a 12-week treatment caused signicant de-
creases in the FBG, 2hPG, and HbA1c levels without any
signicant change in body weight [35]. In that study, in-
sulin resistance, calculated by using a homeostatic model
assessment, was also reduced while
-cell function was
increased signicantly. However, a dose of 1 g/day caused
insignicant changes, and no further increments in the
benecial responses were observed with a dose of 3 g/day,
indicating that 2 g/day was the optimum dose. Bilal et al
reported the highly signicant decreases in the FBG, TC,
LDL-C and TG levels and increases in the HDL-C and the
insulin levels were observed in patients with type 2 diabe-
tes after 40 days of NS seed powder intake [36]. However,
in that study, all mentioned values, except the HDL level,
signicantly reversed again after 40 days of placebo intake.
3.7. Nervous system
Akhondian et al demonstrated that treatment of intracta-
ble pediatric seizures with water extract of black seed (40
mg/kg/8 h) versus placebo, as an adjuvant therapy to anti-
epileptic drugs, led to a signicant reduction in the mean
frequency of seizures [80]. A similar clinical trial done by
the same author had similar outcomes, although TQ (1
mg/kg) was administered as an add-on therapy instead of
water extract of black seed [81]. On the other hand, anoth-
er study conducted by Shawki et al had a dierent result;
after administration of 40 - 80 mg/kg/day of black seed oil
as an adjuvant therapy for 4 weeks, no benecial eects on
the frequency and severity of seizures in intractable epi-
leptic children were observed [82].
In a placebo-controlled clinical trial addressing memory
and cognition, healthy elderly volunteers took a 500-mg
NS capsule twice a day over a period of 9 weeks [83]. At the
end of that period, through special tests, the authors ob-
served improved cognition, memory, and attention. Simi-
larly, another CT performed on healthy adolescent males
aged 14 to 17 years established the modulatory eects on
cognition, mood, and anxiety of NS taken in the form of a
500-mg NS capsule once a day for four weeks [84].
Sangi et al introduced NS administration as a eective
non-opiate treatment for opioid dependence [85]. ey
found that NS treatment oers some advantages in con-
trast with opiate treatments, such as relieving the with-
drawal eects, maintaining the physiological parameters,
and improving appetite.
3.8. Analgesic effects
Huseini et al showed that as compared with the topi-
cal administration of diclofenac, topical administration
of NS oil had signicant therapeutic eects on patients
with cyclic mastalgia without any adverse eects [86]. In
that study, 600 mg of NS oil (in the rst treatment group)
and 20 mg of topical diclofenac (in the second treatment
group) were applied to the painful area twice daily for two
3.9. Dermatology
Vitiligo is an autoimmune skin disease occurring due to
the destruction of skin melanocytes that produce skin pig-
ment. A RCT comparing the ecacy of applying NS oil and
sh oil to the lesions of vitiligo twice a day for six months
indicated that the former is more eective than the latter in
reducing the size of the lesions [39].
Hand eczema is a pruritic papulovesicular dermatitis se-
verely inuencing the patient's quality of life. Youse et al
compared the eects of NS ointment, betamethasone, and
eucerin on the severity of hand eczema and the patients'
quality of life [87]. In that study, for new cases of hand ec-
zema in patients between 18 and 60 years of age the men-
tioned drugs were applied twice daily for 4 weeks. rough
particular measures, the authors concluded that NS may
be as eective as betamethasone in enhancing quality of
life and alleviating the severity of eczema and that both
were more eective than eucerin.
In contrast, for a comparison of the therapeutic eects of
NS oil ointment and aplacebo on patients with atopic der-
matitis (eczema), 20 patients were asked to apply NS oil on
one arm and a placebo on the other every day for 4 weeks
[88]. e authors of that study reported that no meaning-
ful dierence could be found in terms of the parameters
measured, e.g., severity, pruritis, transepidermal water
loss, and skin hydration, between the treatment with NS
oil ointment and with a placebo.
Arsenical keratosis manifests itself in both the palms of
the hands and the soles of the feet due to chronic arsenic
consumption caused by drinking contaminated water.
Taking capsules of NS oil (500 mg) and vitamin E (200 mg)
for eight weeks has been shown to reduce the body’s ar-
senic load, thereby contributing to an overall alleviation of
the symptoms in patients with this disease [89].
3.10. Infectious diseases
Infection with HCV often leads to chronic hepatitis,
which, in turn, results in liver cirrhosis and hepatocellular
carcinomas. A study conducted in Egypt on HCV patients
demonstrated that ethanolic extracts of NS and Zingiber
ocinale (Z. ocinale), alone and together, had bene-
cial eects on HCV patients; i.e., their liver function was
improved and the viral load was decreased [90]. In that
study, a mixture of these extracts was observed to be more
eective than each one alone. Patients included in that
study were treated with capsules containing 500 mg of NS
and/or Z. ocinale twice daily for one month. In a similar
study, HCV patients received capsules of NS oil (450 mg)
three times a day over a 3-month period. at treatment
led to the same results reported in Ref. 90, i.e., decreased
viral load and improved liver function [43].
Onifade et al conrmed that treatment of a sero-positive
human immunodeciency virus (HIV) infected man with
NS concoction (10 mL twice/day for six months) resulted
in the reduction of the viral load to an undetectable level
in 3 months, an elevation of the CD4 count, an allevia-
tion of the symptoms, and a sustained sero-reversion [91].
Similarly, another study conducted by the same author on
a sero-positive HIV infected woman revealed the ecacy
of NS and honey therapy (10 mL thrice/day for 1 year)
for sustained sero-reversion [92]. ese eects can be as-
cribed to the probable virucidal activity of NS [91].
e helicobacter pylori (H. pylori) bacterium can cause
many diseases, such as peptic ulcers and gastric cancer.
Infection with H. pylori has a high prevalence worldwide.
Salem et al stated that in a four-week course, the ecacy
of NS powder (2 g/day) administered together with ome-
prazole to eradicate an H. pylori infection in non-ulcer
dyspeptic patients was relatively the same as that of triple
therapy, although 1 g/day or 3 g/day of NS powder given
together with omeprazole was not as eective, indicating
that the optimal dose of NS was 2 g/day [93]. (Triple thera-
py includes clarithromycin, amoxicillin, and omeprazole.)
In a study conducted on children who were infected with 115
cestodes, the ecacy of single oral administration of NS
powdered seeds and ethanolic extract (40 mg/kg body
weight) was proven to reduce the percentage of fecal eggs
per gram, which means NS has an anti-cestodal eect
[45]. Furthermore, in a RCT in which 100 infected women
were included, the therapeutic eects of black seed cap-
sules (500 mg twice daily) used together with clotrimazole
vaginal cream on C. albicans vaginitis were compared
with those of placebo capsules (500 mg twice daily) used
in combination with the same vaginal cream [94]. In that
study, after a 7-day treatment, the black seed capsules
used with clotrimazole vaginal cream were more impres-
sive in reducing the symptoms of the disease, such as vagi-
nal itching, discharge, irritation, vulvovaginal redness and
inammation [94].
3.11. Reproductive system
Kolahdooz et al proved that treatment of infertile Iranian
men with 2.5 mL of NS oil twice a day for two months, in
contrast with a placebo treatment in the same manner,
could enhance sperm parameters, including sperm count,
motility and morphology, semen volume, pH, and its
round cells [41]. Other benecial eects of NS on Leydig
cells, reproductive organs, and sexual hormones in infer-
tile men have also been conrmed [95].
3.12. Respiratory system
As for lower respiratory tract illnesses (LRTI), Boskabady
et al investigated the antiasthmatic eects of NS boiled
extract (50 and 100 mg/kg), theophylline (5 mg/kg), and
salbutamol (200 μg) [96]. In that study, 15 asthmatic pa-
tients were recruited, and each patient received one of
these 4 treatments in random order at intervals of 48 hours
for 2 weeks. e results of that study demonstrated that
in spite of the fact that both doses of NS boiled extract
showed bronchodilatory eects, their ecacies for pul-
monary function test (PFT) elevation were less than those
of theophylline and salbutamol. e results also revealed
the prophylactic eects of NS boiled extract on adult asth-
matic patients. In another study, over a 3-month period,
the daily intake of 15 mL/kg of 0.1% NS boiled extract led
to more impressive improvements in the PFT parameters
and alleviations of the symptoms of asthma than the intake
of the placebo solution did [97]. Ahmad et al conducted a
study on 5- to15-year-old LRTI patients with wheezing and
investigated the benecial impacts of the standard treat-
ment alone and the standard treatment combined with the
use of NS oil [98]. e authors of that study concluded that
the standard treatment when administered with NS oil (0.1
mg/kg for 14 days) had more benecial eects in reducing
the pulmonary index and improving the peak expiratory
ow rate [98]. In another study, daily administration of
0.375 mL/kg of 50% NS boiled water extract, as compared
with a placebo solution to victims of chemical warfare, as
compared with a placebo solution, for two months eect-
ed meaningful improvements in the PFT measures and the
respiratory symptoms, indicating that the use of NS had a
prophylactic impact on victims of chemical warfare [99].
Allergic rhinitis (AR) is an inammatory response of the
nasal mucosa to natural allergens and is characterized by
sneezing, rhinorrhea, nasal congestion, and itching [47,
100]. Moreover, a study comparing the therapeutic eects
of NS seeds (250 mg/day) and montelukast (10 mg/day) on
patients with seasonal allergic rhinitis over a course of two
weeks illustrated that both improved the daytime and oph-
thalmic symptoms considerably, although NS was more
ecient in alleviating the nighttime symptoms [46]. Simi-
larly, Nikakhlagh et al showed the positive eects of NS oil
capsule consumption over four weeks on the symptoms of
allergic rhinitis, i.e., nasal mucosal congestion, nasal itch-
ing, runny nose, sneezing attacks, turbinate hypertrophy,
and mucosal pallor [100]. Like the previous studies, that
of Alsamarai et al demonstrated that nasal drops of NS oil,
in comparison with nasal drops of ordinary food oil, could
signicantly improve the symptoms of AR patients, as well
as their ability to tolerate exposure to allergens [47]. In that
study, each drop comprised 15 mL of oil, and the patients
applied 2 drops nasally (one in each nostril) 3 times dai-
ly for 6 weeks. In an additional study of AR patients who
underwent a month of allergen-specic immunotherapy
and then received treatment with NS seeds (2 g/d) dur-
ing the next month, in contrast with the AR patients who
only received immunotherapy for two months, the former
showed more progress in their immune status, e.g., PMN
functions and CD8 counts [101]. at study showed that
NS administration contributed to a more eective immu-
notherapy. According to a study by Oysu et al, some of the
nasal symptoms of geriatric patients, for example, nasal
dryness, obstruction, and crusting, can be signicantly
improved by using NS oil [102].
As for patients with tonsillopharyngitis, the results of a
study by Dirjomuljono et al indicated that NSPN capsules
containing 360 mg of NS and 50 mg of Phyllanthus niruri
extracts, as compared with a placebo, if given three times
a day for 7 days to patients with acute tonsillopharyngitis,
could signicantly alleviate the symptoms of the disease
due to their anti-inammatory and immuno-modulatory
eects [44]. In another study, which was undertaken on
patients with inhalation allergy, the benecial impacts of
NS oil on the immune status of those patients, including
enhancement of the NK cell count and percentage of lym-
phocytes, were conrmed [103].
3.13. Skeletal system
Rheumatoid arthritis (RA) is a chronic systemic disease
characterized by inammation of the joints, degeneration
of collagen bers in mesenchymal tissues, and atrophy of
bones. Although the etiology is not well understood, au-
toimmunity seems to play a role in the etiology of RA. A
study on 40 female RA patients who received placebo cap-
sules twice a day in the rst month and 500-mg NS oil cap-
sules twice a day in the next month observed that the use
of NS oil capsules notably improved the disease’s activity
score and alleviated its symptoms, which could be attrib-
uted to the modulatory eect of NS on the immune system
A clinical trial conducted on osteopenic postmenopausal
women showed that the intake of NS oil (0.05 cc/kg/d) for
three months had no considerable eects on bone turno-
ver markers [40]. Furthermore, in another clinical trial,
in which 15 osteoporotic postmenopausal women were
included, no benecial eects of consuming NS extract
(0.05 mL/kg/d for three months) on bone turnover were
observed [105].
3.14. Gastrointestinal system
Celiac disease (CD) is characterized by increased sen-
sitivity to gluten and by inammation and destruction of
the small intestine mucosa due to an autoimmune mecha-
nism. In a study by Osman et al, the prescription of a glu-
ten free diet (GFD) together with the consumption of a
NS oil capsule (450 mg) twice daily as dietary supplement
for one year was more eective than a GFD alone in the
treatment of patients with iron deciency anemia associ-
ated with refractory CD; i.e., the hematological and im-
munological indices and the duodenal histology recovery
were improved [106]. Dermatitis herpetiformis (DH) is an
autoimmune skin disease caused by CD and is character-
ized by itchiness, a burning sensation, and chronic derma-
titis. Similar to the former CT, adding NS oil capsules to a
GFD for a period of 6 months was found to enhance the
ecacy of a GFD in the treatment of the disease [107]. Fur-
thermore, Mohtashami et al. reported that administration
of a honey-based formulation of NS oil (5 mL NS oil/day),
in comparison with a placebo, for 8 weeks could signi-
cantly improve the symptoms, such as dyspepsia severity,
and decrease the rate of H. pylori infection in functional
dyspeptic patients [42].
3.15. Anti-toxicity effects
Leukemia is a tumoral growth of WBCs in the bone mar-
row and is caused by a malignant neoplasm of hemat-
opoietic stem cells. In ALL, which is the most common
childhood malignancy [108], increased numbers of lym-
phoblasts are present in the circulating blood and in dier-
ent tissues and organs [48]. A study by Hagag et al reported
that NS oil (80 mg/kg/day) administered for one week after
each methotrexate treatment could reduce hepatotoxicity
and improve the survival rate in ALL children undergoing
that treatment [108].
4. Discussion
is review article summarized dierent studies on the
clinical uses of NS and TQ in the prevention and the treat-
ment of dierent diseases. Results indicated that NS has
benecial eects when used in the therapies for various
diseases, including cardiovascular, nervous system, skin,
infectious, reproductive system, respiratory system, skel-
etal system, and gastrointestinal diseases. Taken together,
the role of NS in the treatment of dierent diseases is dis-
cussed in the following sentences.
Dyslipidemia plays an important role in the genesis of
cardiovascular diseases (CVDs) [71], and hypercholeste-
rolemia is the most important risk factor for atheroscle-
rosis [72]. Lipid abnormalities are accountable for 56% of
patients with heart disease and 18% of those with an in-
farction; further, it is associated with one third of deaths
worldwide. In this article, we reviewed 19 clinical trials
that reported the ameliorative eect of NS on the lipid pro-
le. is nding shows that the use of NS supplements can
improve the lipid prole and prevent CVDs both in healthy
people and hyperlipidemic patients. e exact mecha-
nisms of the lipid-modifying eects of NS are not known,
but might be associated with the inhibition of intestinal
cholesterol absorption, decreased hepatic cholesterol syn-
thesis, and up-regulation of LDL receptors [74].
On the other hand, dyslipidemia is an important risk fac-
tor responsible for cardiovascular disease in patients with
diabetes [109], so alleviation/elimination of lipid abnor-
malities is important in the prevention of the complica-
tions of diabetes [79]. us, keeping the lipid prole of dia-
betic patients in the normal range can improve their health
status, and NS intake, in combination with anti-diabetics
and statins or brates, can help diabetic patients to control
both dyslipidemia and blood sugar. We also reported the
results of 13 clinical trials that presented data on the hy-
poglycemic eect of NS, 8 of which included patients with
insulin resistance. e results showed that the use of black
seed could decrease the HbA1c (5 studies) and the PPBG
(2 studies) levels signicantly.
Obesity is typically associated with increased risk factors
of CVDs. erefore, a therapeutic approach that aims to
control body weight and the metabolic prole might be ef-
fective in preventing CVDs [62]. e results of this review
demonstrate that the use of NS may have a weight-lose ef-
fect in obese men and women. Because of the lipid-mod-
ifying, hypoglycemic, and weight-lowering eects of black
seed, its use in the treatment of patients with metabolic
syndrome may be benecial [21].
According to some studies reviewed, NS may be a useful
herb for improving sexual function because of its inhibito-
ry eect on prolactin [51] and excitatory eect on testoster-
one [33]. In addition, spermatogenesis can be stimulated
by NS [95]. Consequently, it presents a good option for use
in the treatment of infertile men. However, more studies
are needed due to the lack of an adequate number of stud-
ies proving this eect.
TQ has an antioxidant role, improves the body's defense
system, induces apoptosis, and controls the Akt pathway
[7]. Immune system modulation is one of the most impor-
tant properties of NS, and a number of studies have been
done in order to prove this signicant eect. In this article,
we reviewed ve studies that directly showed the immuno-
modulatory eect of NS [39, 44, 104, 106, 107]. In addition,
other investigations have demonstrated that NS may be an
optimum choice for treating patients with allergy-related
diseases, such as asthma, atopic eczema and allergic rhini-
tis [110].
Moreover, the anti-nociceptive eect of NS has been
widely investigated in animal models, and a few studies 117
have evaluated that eect in humans. In this paper, the
anti-microbial activities of NS against bacteria, viruses,
and parasites have also been highlighted. e conclusion
is that it can be used in the treatment of infectious diseases
e existing drugs for some diseases produce adverse side
eects, do not lead to complete recovery, or are sometimes
expensive. us, herbal medicines, such as NS, can be use-
ful alternatives; however, before such herbal medicines are
used extensively, many RCTs should be conducted in or-
der to evaluate and conrm the eects of herbal medicines
[46, 48, 108]. One obvious example is sero-reversion in
HIV-infected patients. Highly active anti-retroviral therapy
does not cause sero-reversion in HIV-infected patients.
Onifade et al proved that NS contributes to sustained sero-
reversion in patients with HIV infection [91, 92].
Some authorities, despite achieving positive outcomes
for the features of NS, suggest further investigations with
larger samples and groups, diverse doses of NS, and longer
periods of study [42, 83-85, 93, 97-99]. After the benecial
eects of NS have been conrmed, it can be used in treat-
ment protocols. In contrast, some authors have reached
results that conict with the traditional beliefs about NS.
Actually, the evidence for the positive eects of NS in the
treatment of osteopenic postmenopausal women and
intractable epileptic children is conicting [40, 82, 105].
erefore, more studies should be planned in these situ-
5. Conclusion
In conclusion, the use of black seeds and their active
constituent TQ has been shown to have multiple useful
eects in the treatments of patients with several diseases,
such as inammatory and auto-immune disorders, as well
as metabolic syndrome. In this study, we also reviewed
other advantages of NS, e.g., its antimicrobial properties,
anti-nociceptive and anti-epileptic impacts, etc. We found
that the side eects of this herbal medicine did not ap-
pear serious, so it can be applied in clinical trials because
most of its major eects have been shown to be benecial.
Some properties of NS, such as its hypoglycemic, hypoli-
pidemic, and bronchodilatory properties, are suciently
understood so that NS can be used for subsequent phases
of clinical trials or for drug development. However, most
of the other eects and applications of NS require further
clinical and animal studies.
e authors thank Mashhad University of Medical Sci-
ences, Mashhad, Iran.
Conflict of interest
e authors declare that there are no conicts of interest.
Ziaee T, Moharreri N, Hosseinzadeh H. Review of phar-
macological and toxicological eects of Nigella sativa
and its active constituents. J Med Plants. 2012;2(42):16-
Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Cola-
gar A, Sisakhtnezhad S. ymoquinone and its thera-
peutic potentials. Pharmacol Res. 2015;95-96:138-58.
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK,
Siddique NA, et al. A review on therapeutic potential of
Nigella sativa: a miracle herb. Asian Pac J Trop Biomed.
Mollazadeh H, Hosseinzadeh H. e protective eect
of Nigella sativa against liver injury: a review. Iran J Ba-
sic Med Sci. 2014;17(12):958-66.
Shaq H, Ahmad A, Masud T, Kaleem M. Cardio-pro-
tective and anti-cancer therapeutic potential of Nigella
sativa. Iran J Basic Med Sci. 2014;17(12):967-79.
Butt MS, Sultan MT. Nigella sativa: reduces the
risk of various maladies. Crit Rev Food Sci Nutr.
Khan MA, Chen HC, Tania M, Zhang DZ. Anticancer
activities of Nigella sativa (black cumin). Afr J Tradit
Complement Altern Med. 2011;8(5):226-32.
Banerjee S, Padhye S, Azmi A, Wang Z, Philip PA,
Kucuk O, et al. Review on molecular and therapeu-
tic potential of thymoquinone in cancer. Nutr Cancer.
Abukhader MM. ymoquinone in the clinical treat-
ment of cancer: fact or ction?. Pharmacogn Rev.
Forouzanfar F, Bazzaz BSF, Hosseinzadeh H. Black
cumin (Nigella sativa) and its constituent (thymoqui-
none): a review on antimicrobial eects. Iran J Basic
Med Sci. 2014;17(12):929-38.
Hosseinzadeh H, Fazly Bazzaz BS, Haghi MM. Anti-
bacterial activity of total extracts and essential oil of
Nigella sativa L. seeds in mice. Pharmacologyonline.
Amin B, Hosseinzadeh H. Black Cumin (Nigella sativa)
and its active constituent, thymoquinone: an overview
on the analgesic and anti-inammatory eects. Planta
Med. 2015;82(1-2):8-16.
Amin B, Taheri MM, Hosseinzadeh H. Eects of intra-
peritoneal thymoquinone on chronic neuropathic pain
in rats. Planta Med. 2014;80(15):1269-77.
Ali BH, Blunden G. Pharmacological and toxico-
logical properties of Nigella sativa. Phytother Res.
Hosseinzadeh H, Eskandari M, Ziaee T. Antitussive ef-
fect of thymoquinone, a constituent of Nigella sativa
seeds, in guinea pigs. Pharmacologyonline. 2008;2:480-
Salem ML. Immunomodulatory and therapeutic prop-
erties of the Nigella sativa L. seed. Int Immunopharma-
col. 2005;5(13-14):1749-70.
Hosseinzadeh H, Taiari S, Nassiri-Asl M. Eect of
thymoquinone, a constituent of Nigella sativa L., on
ischemia-reperfusion in rat skeletal muscle. Naunyn-
Schmiedebergs Arch Pharmacol. 2012;385(5):503-8.
Hosseinzadeh H, Moghim FF, Mansouri S, Mansouri
T. Eect of Nigella sativa seed extracts on ischemia-
reperfusion in rat skeletal muscle. Pharmacologyon-
line 2007;2:326-35.
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR,
Ziaee T. Eect of thymoquinone and Nigella sativa
seeds oil on lipid peroxidation level during global cer-
ebral ischemia-reperfusion injury in rat hippocampus.
Phytomedicine. 2007;14(9):621-7.
Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al ani
H. Cardiovascular benets of black cumin (Nigella sati-
va). Cardiovasc Toxicol. 2013;13(1):9-21.
Razavi B, Hosseinzadeh H. A review of the eects
of Nigella sativa L. and its constituent, thymoqui-
none, in metabolic syndrome. J Endocrinol Invest.
Parvardeh S, Nassiri-Asl M, Mansouri SMT, Hossein-
zadeh H. Study on the anticonvulsant activity of thy-
moquinone, the major constituent of Nigella sativa L.
seeds, through intracerebroventricular injection. J Med
Plants. 2005;4:45-52.
Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri
MT. Intracerebroventricular administration of thymo-
quinone, the major constituent of Nigella sativa seeds,
suppresses epileptic seizures in rats. Med Sci Monit.
Hosseinzadeh H, Parvardeh S. Anticonvulsant eects
of thymoquinone, the major constituent of Nigella
sativa seeds, in mice. Phytomedicine. 2004;11(1):56-64.
Pourbakhsh H, Taghiabadi E, Abnous K, Hariri AT,
Hosseini SM, Hosseinzadeh H. Eect of Nigella sativa
xed oil on ethanol toxicity in rats. Iran J Basic Med Sci.
Mehri S, Shahi M, Razavi BM, Hassani FV, Hossein-
zadeh H. Neuroprotective eect of thymoquinone in
acrylamideinduced neurotoxicity in wistar rats. Iran J
Basic Med Sci. 2014;17(12):1007-11.
Javidi S, Razavi BM, Hosseinzadeh H. A review of
neuropharmacology eects of Nigella sativa and its
main component, thymoquinone. Phytother Res.
Havakhah S, Sadeghnia HR, Hajzadeh MA, Roshan NM,
Shaee S, Hosseinzadeh H, et al. Eect of Nigella sativa
on ischemia-reperfusion induced rat kidney damage.
Iran J Basic Med Sci. 2014;17(12):986-92.
Hosseinzadeh H, Montahaei R. Protective eect of
Nigella sativa L. extracts and thymoquinone, its ac-
tive constituent, on renal ischemia-reperfusion-in-
duced oxidative damage in rats. Pharmacologyonline.
Amini M, Huseini HF, Mohtashami R, Ghamarchehre
MA. Hypolipidemic eects of Nigella sativa L. seeds
oil in healthy volunteers: a randomized, double-
blind, placebo-controlled clinical trial. J Med Plants.
Huseini HF, Amini M, Mohtashami R, Ghamarchehre
ME, Sadeqhi Z, Kianbakht S, et al. Blood pressure low-
ering eect of Nigella sativa L. seed oil in healthy vol-
unteers: a randomized, double-blind, placebo-control-
led clinical trial. Phytother Res. 2013;27(12):1849-53.
Bilal A, Masud T, Uppal AM, Naveed AK. Eects of Nig-
ella sativa oil on some blood parameters in type 2 dia-
betes mellitus patients. Asian J Chem. 2009;21(7):5373-
Datau EA, Wardhana, Surachmanto EE, Pandelaki K,
Langi JA, Fias. Ecacy of Nigella sativa on serum free
testosterone and metabolic disturbances in central
obese male. Acta Med Indones. 2010;42(3):130-4.
Qidwai W, Hamza HB, Qureshi R, Gilani A. Eective-
ness, safety, and tolerability of powdered Nigella sativa
(kalonji) seed in capsules on serum lipid levels, blood
sugar, blood pressure, and body weight in adults: re-
sults of a randomized, double-blind controlled trial. J
Altern Complement Med. 2009;15(6):639-44.
Bamosa AO, Kaatabi H, Lebda FM, Elq AM, Al-Sultan A.
Eect of Nigella Sativa seeds on the glycemic control of
patients with type 2 diabetes mellitus. Indian J Physiol
Pharmacol. 2010;54(4):344-54.
Bilal A, Masud T, Uppal AM. BS5-5 Black seed (Nigella
sativa) regulates glucose, insulin level and lipid pro-
le in patients with type 2 diabetes. Diabetes Res Clin
Pract. 2008;79:19-20.
El-Shamy KA, Mosa MMA, El-Nabarawy SK, El-Qattan
M. Eect of Nigella sativa tea in type 2-diabetic patients
as regards glucose homeostasis, liver and kidney func-
tions. J Appl Sci Res. 2011;7(12):2524-34.
Dehkordi FR, Kamkhah AF. Antihypertensive eect of
Nigella sativa seed extract in patients with mild hyper-
tension. Fundam Clin Pharmacol. 2008;22(4):447-52.
Ghorbanibirgani A, Khalili A, Rokhafrooz D. Compar-
ing Nigella sativa oil and sh oil in treatment of vitiligo.
Iran Red Crescent Med J. 2014;16(6):e4515.
Valizadeh N, Zakeri HR, Shaee A, Sarkheil P, Heshmat
R, Larijani B. e eect of Nigella sativa extract on bio-
chemical bone markers in osteopenic postmenopausal
women. Iran J Endocrinol Metab. 2009;10(6):571-80.
Kolahdooz M, Nasri S, Modarres SZ, Kianbakht S,
Huseini HF. Eects of Nigella sativa L. seed oil on ab-
normal semen quality in infertile men: a randomized,
double-blind, placebo-controlled clinical trial. Phyto-
medicine. 2014;21(6):901-5.
Mohtashami R, Huseini HF, Heydari M, Amini M, Sad-
eqhi Z, Ghaznavi H, et al. Ecacy and safety of honey
based formulation of Nigella sativa seed oil in func-
tional dyspepsia: a double blind randomized control-
led clinical trial. J Ethnopharmacol. 2015;175:147-52.
Barakat EMF, El Wakeel LM, Hagag RS. Eects of Nig-
ella sativa on outcome of hepatitis C in Egypt. World J
Gastroenterol. 2013;19(16):2529-36.
Dirjomuljono M, Kristyono I, Tjandrawinata RR, No-
arny D. Symptomatic treatment of acute tonsillo-phar-
yngitis patients with a combination of Nigella sativa
and Phyllanthus niruri extract. Int J Clin Pharmacol
er. 2008;46(6):295-306.
Akhtar MS, Riat S. Field trial of Saussurea lappa roots
against nematodes and Nigella sativa seeds against
cestodes in children. J Pak Med Assoc. 1991;41(8):185-
Ansari MA, Ansari NA, Junejo SA. Montelukast ver-
sus Nigella sativa for management of seasonal allergic
rhinitis: a single blind comparative clinical trial. Pak J
46. 119
Med Sci. 2010;26(2):249-54.
Alsamarai AM, Abdulsatar M, Ahmed Alobaidi AH.
Evaluation of topical black seed oil in the treatment of
allergic rhinitis. Antiinamm Antiallergy Agents Med
Chem. 2014;13(1):75-82.
Dogar MZUH, Adi H, Akhtar MS, Sheikh MA. Prelimi-
nary assessment of ecacy of Nigella sativa seeds in
acute lymphoblastic leukemia in local children. Phar-
macologyonline. 2009;2:769-77.
Arslan E, Sayin S, Demirbas S, Cakar M, Somak NG,
Yesilkaya S, et al. A case study report of acute renal fail-
ure associated with Nigella sativa in a diabetic patient.
J Integr Med. 2013;11(1):64-6.
Bamosa A. Nigella sativa is a safe herbal product. J In-
tegr Med. 2014;12(1):66.
Ibraheim ZZ. Eect of Nigella sativa seeds and total oil
on some blood parameters in female volunteers. Saudi
Pharm J. 2002;10:54-9.
Gelot P, Bara-Passot C, Gimenez-Arnau E, Bene-
ton N, Maillard H, Celerier P. [Bullous drug erup-
tion with Nigella sativa oil]. Ann Dermatol Venereol.
2012;139(4):287-91. French.
Al-Jenoobi FI, Al-ukair AA, Abbas FA, Ansari MJ,
Alkharfy KM, Al-Mohizea AM, et al. Eect of black seed
on dextromethorphan O- and N-demethylation in hu-
man liver microsomes and healthy human subjects.
Drug Metab Lett. 2010;4(1):51-5.
Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria
P. Nonalcoholic fatty liver disease: a precursor of the
metabolic syndrome. Dig Liver Dis. 2015;47(3):181-90.
Kim B, Feldman EL. Insulin resistance as a key link for
the increased risk of cognitive impairment in the meta-
bolic syndrome. Exp Mol Med. 2015;47:e149.
Najmi A, Haque SF, Naseeruddin M, Khan RA. Eect
of Nigella sativa oil on various clinical and biochemi-
cal parameters of metabolic syndrome. Int J Diabetes
Metab. 2008;16:85-7.
Amin F, Islam N, Anila N, Gilani AH. Clinical ecacy
of the co-administration of Turmeric and Black seeds
(Kalongi) in metabolic syndrome - a double blind ran-
domized controlled trial- TAK-MetS trial. Complement
er Med. 2015;23(2):165-74.
Lati LA, Parhizkar S, Dollah MA, Tajuddin Syed Has-
san S. Alternative supplement for enhancement of re-
productive health and metabolic prole among peri-
menopausal women: a novel role of Nigella sativa. Iran
J Basic Med Sci. 2014;17(12):980-5.
Najmi A, Nasiruddin M, Khan RA, Haque SA. era-
peutic eect of Nigella sativa in patients of poor glyc-
emic control. Asian J Pharm Clin Res. 2012;5:224-8.
Lee MJ, Wu Y, Fried SK. Adipose tissue heterogeneity:
implication of depot dierences in adipose tissue for
obesity complications. Mol Aspects Med. 2013;34(1):1-
Namazi N, Mahdavi R, Alizadeh M, Farajnia S. Oxida-
tive stress responses to Nigella sativa oil concurrent
with a low-calorie diet in obese women: a randomized,
double-blind controlled clinical trial. Phytother Res.
Mahdavi R, Namazi N, Alizadeh M, Farajnia S. Eects
of Nigella sativa oil with a low-calorie diet on cardi-
ometabolic risk factors in obese women: a randomized
controlled clinical trial. Food Funct. 2015;6(6):2041-8.
Ni WQ, Liu XL, Zhuo ZP, Yuan XL, Song JP, Chi HS, et
al. Serum lipids and associated factors of dyslipidemia
in the adult population in Shenzhen. Lipids Health Dis.
Moeen-ud-din H, Murad S, Fatima A. Placebo control-
led study on comparison of eects of Nigella sativa and
nicotinic acid along with low fat diet and physical ex-
ercise on LDL-cholesterol and HDL-cholesterol. Pak J
Med Health Sci. 2014;8:306-9.
Fatima A, Shad MN, Asrar A, Murad S. Eects of Nigella
sativa on HDL-c & body weight. Pak J Med Health Sci.
Ibrahim RM, Hamdan NS, Mahmud R, Imam MU, Saini
SM, Rashid SN, et al. A randomised controlled trial on
hypolipidemic eects of Nigella Sativa seeds powder in
menopausal women. J Transl Med. 2014;12:82.
Ibrahim RM, Hamdan NS, Ismail M, Saini SM, Abd
Rashid SN, Abd Lati L, et al. Protective eects of Ni-
gella sativa on metabolic syndrome in menopausal
women. Adv Pharm Bull. 2014;4(1):29-33.
Mathews MJ, Liebenberg L, Mathews EH. e mecha-
nism by which moderate alcohol consumption inu-
ences coronary heart disease. Nutr J. 2015;14:33.
Tasawar Z, Siraj Z, Ahmad N, Mushtaq H. e eects of
Nigella sativa (Kalonji) on lipid prole in patients with
stable coronary artery disease in Multan, Pakistan. Pak
J Nut. 2011;10:162-7.
Bamosa AO, Basil A, Sowayan AA, Sowayan SA. Eect
of oral ingestion of Nigella sativa seeds on some blood
parameters. Saudi Pharm J. 2007;2:126-9.
Ahmad Alobaidi AH. Eect of Nigella sativa and Al-
lium sativum coadminstered with simvastatin in dys-
lipidemia patients: a prospective, randomized, double-
blind trial. Antiinamm Antiallergy Agents Med Chem.
Sabzghabaee AM, Dianatkhah M, Sarrafzadegan N,
Asgary S, Ghannadi A. Clinical evaluation of Nigella
sativa seeds for the treatment of hyperlipidemia: a ran-
domized, placebo controlled clinical trial. Med Arch.
Roufogalis B, Sekhon B. No statistically signicant ef-
fects of powdered Nigella sativa (kalonji) seed on se-
rum lipid levels, blood sugar, blood pressure or body
weight in adults. Focus Altern Complement er.
Asgary S, Sahebkar A, Goli-malekabadi N. Ameliorative
eects of Nigella sativa on dyslipidemia. J Endocrinol
Invest. 2015;38(10):1039-46.
Sahebkar A, Beccuti G, Simental-Mendia LE, Nobili V,
Bo S. Nigella sativa (black seed) eects on plasma li-
pid concentrations in humans: a systematic review and
meta-analysis of randomized placebo-controlled trials.
Pharmacol Res. 2016;106:37-50.
Kaatabi H, Bamosa AO, Badar A, Al-Elq A, Abou-Ho-
zaifa B, Lebda F, et al. Nigella sativa improves glycemic
control and ameliorates oxidative stress in patients with
type 2 diabetes mellitus: placebo controlled participant
blinded clinical trial. PLoS One. 2015;10(2):e0113486.
Heshmati J, Namazi N, Memarzadeh MR, Taghizadeh
M, Kolandooz F. Nigella sativa oil aects glucose me-
tabolism and lipid concentrations in patients with type
2 diabetes: a randomized, double-blind, placebo-con-
trolled trial. Food Res Int. 2015;70:87-93.
Najmi A, Nasiruddin M, Khan R, Haque SF. Eect of Ni-
gella sativa oil on various clinical and biochemical pa-
rameters of insulin resistance syndrome. Int J Diabetes
Dev Ctries. 2008;28(1):11-4.
Hadi S, Mirmiran P, Hosseinpour-Niazi S, Hedayati M,
Azizi F. Eect of Nigella sativa oil extract on lipid pro-
les in type 2 diabetic patients: a randomized, double
blind, placebo-controlled clinical trial. Iran J Endocri-
nol Metab. 2015;16(6):411-8.
Akhondian J, Parsa A, Rakhshande H. e eect of Nig-
ella sativa L. (black cumin seed) on intractable pediat-
ric seizures. Med Sci Monit. 2007;13(12):CR555-9.
Akhondian J, Kianifar H, Raoofziaee M, Moayedpour A,
Toosi MB, Khajedaluee M. e eect of thymoquinone
on intractable pediatric seizures (pilot study). Epilepsy
Res. 2011;93(1):39-43.
Shawki M, El Wakeel LM, Shatla R, El-Saeed G, Ibrahim
S, Badary O. e clinical outcome of adjuvant therapy
with black seed oil on intractable paediatric seizures: a
pilot study. Epileptic Disord. 2013;15(3):295-301.
Bin Sayeed MS, Asaduzzaman M, Morshed H, Hos-
sain MM, Kadir MF, Rahman MR. e eect of Nigella
sativa Linn. seed on memory, attention and cogni-
tion in healthy human volunteers. J Ethnopharmacol.
Bin Sayeed MS, Shams T, Fahim Hossain S, Rahman
MR, Mostofa A, Fahim Kadir M, et al. Nigella sativa L.
seeds modulate mood, anxiety and cognition in healthy
adolescent males. J Ethnopharmacol. 2014;152(1):156-
Sangi S, Ahmed SP, Channa MA, Ashfaq M, Mastoi
SM. A new and novel treatment of opioid dependence:
Nigella sativa 500 mg. J Ayub Med Coll Abbottabad.
Huseini HF, Kianbakht S, Mirshamsi MH, Zarch AB. Ef-
fectiveness of topical Nigella sativa seed oil in the treat-
ment of cyclic mastalgia: a randomized, triple-blind,
active, and placebo-controlled clinical trial. Planta
Med. 2016;82(4):285-8.
Youse M, Barikbin B, Kamalinejad M, Abolhasani E,
Ebadi A, Younespour S, et al. Comparison of therapeu-
tic eect of topical Nigella with betamethasone and
eucerin in hand eczema. J Eur Acad Dermatol Vener-
eol. 2013;27(12):1498-504.
Stern T, Bayerl C. Black seed oil ointment - a new ap-
proach for the treatment of atopic dermatitis?. Aktuelle
Derm. 2002;28(3):74-9.
Bashar T, Misbahuddin M, Hossain MA. A double-
blind, randomize, placebo-control trial to evaluate the
eect of Nigella sativa on palmer arsenical keratosis
patients. Bangladesh J Pharmacol. 2014;9:15-21.
Abdel-Moneim A, Morsy BM, Mahmoud AM, Abo-Seif
MA, Zanaty MI. Benecial theraputic eects of Nigella
sativa and/or Zingiber ocinale in HCV patients in
Egypt. Excli J. 2013;12:943-55.
Onifade AA, Jewell AP, Adedeji WA. Nigella sativa con-
coction induced sustained seroreversion in HIV patient.
Afr J Tradit Complement Altern Med. 2013;10(5):332-5.
Onifade AA, Jewell AP, Okesina AB. Seronegative con-
version of an HIV positive subject treated with Nigella
sativa and honey. Afr J Infect Dis. 2015;9(2):47-50.
EM Salem, Yar T, Bamosa AO, Al-Quorain A, Yasawy
MI, Alsulaiman RM, et al. Comparative study of Nigella
Sativa and triple therapy in eradication of Helicobacter
Pylori in patients with non-ulcer dyspepsia. Saudi J
Gastroenterol. 2010;16(3):207-14.
Fard FA, Zahrani ST, Bagheban AA, Mojab F. era-
peutic eects of Nigella Sativa Linn (Black Cumin)
on Candida albicans vaginitis. Arch Clin Infect Dis.
Mandavi R, Heshmati J, Namazi N. Eects of black
seeds (Nigella sativa) on male infertility: a systematic
review. J Herb Med. 2015;5(3):133-9.
Boskabady MH, Mohsenpoor N, Takaloo L. Antiasth-
matic eect of Nigella sativa in airways of asthmatic
patients. Phytomedicine. 2010;17(10):707-13.
Boskabady MH, Javan H, Sajady M, Rakhshandeh H.
e possible prophylactic eect of Nigella sativa seed
extract in asthmatic patients. Fundam Clin Pharmacol.
Ahmad J, Khan RA, Malik MA. A study of Nigella sativa
oil in the management of wheeze associated lower res-
piratory tract illness in children. Afr J Pharm Pharma-
col. 2009;3(5):248-51.
Boskabady MH, Farhadi J. e possible prophylactic
eect of Nigella sativa seed aqueous extract on res-
piratory symptoms and pulmonary function tests on
chemical war victims: a randomized, double-blind,
placebo-controlled trial. J Altern Complement Med.
Nikakhlagh S, Rahim F, Aryani FH, Syahpoush A,
Brougerdnya MG, Saki N. Herbal treatment of allergic
rhinitis: the use of Nigella sativa. Am J Otolaryngol.
Isik H, Cevikbas A, Gurer US, Kiran B, Uresin Y, Raya-
man P, et al. Potential adjuvant eects of Nigella sativa
seeds to improve specic immunotherapy in allergic
rhinitis patients. Med Princ Pract. 2010;19(3):206-11.
Oysu C, Tosun A, Yilmaz HB, Sahin-Yilmaz A, Korkmaz
D, Karaaslan A. Topical Nigella sativa for nasal symp-
toms in elderly. Auris Nasus Larynx. 2014;41(3):269-72.
Deurer A, Schleicher P, Kalus U, Pruß A, Kiesewetter H.
Eect of black cumin oil on the immune status of pa-
tients with inhalation energy. Biol Med. 2002;31:75-8.
Gheita TA, Kenawy SA. Eectiveness of Nigella sativa
oil in the management of rheumatoid arthritis pa-
tients: a placebo controlled study. Phytother Res.
Valizadeh N, Zakeri HR, Amin Asna G, Shaee A,
Sarkhail P, Heshmat R, et al. Impact of black seed
(Nigella sativa) extract on bone turnover markers in
postmenopausal women with osteoporosis. Daru.
Osman MT, Taha BI, Al-Duboni G, Muhamed LA. Im-
munomodulatory eect of Nigella sativa oil treatment
in iron deciency anemia caused by refractory coeliac
disease. Res J Pharm Biol Chem Sci. 2012;3:887-95.
Osman MT, Kutty MK. Immunotherapeutic application
107. 121
of Nigella sativa oil in management of dermatitis her-
petiformis associated with refractory coeliac disease.
Res J Pharm Biol Chem Sci. 2013;4:1181-6.
Hagag AA, AbdElaal AM, Elfaragy MS, Hassan SM, El-
zamarany EA. erapeutic value of black seed oil in
methotrexate hepatotoxicity in Egyptian children with
acute lymphoblastic leukemia. Infect Disord Drug Tar-
gets. 2015;15(1):64-71.
Qidwai W, Ashfaq T. Eect of dietary supplementa-
tion of black seed (N. Sativa L.) on lipid prole of pa-
tients suering from diabetes. Antiinamm Antiallergy
Agents Med Chem. 2014;13(1):3-8.
Kalus U, Pruss A, Bystron J, Jurecka M, Smekalova A,
Lichius JJ, et al. Eect of Nigella sativa (black seed) on
subjective feeling in patients with allergic diseases.
Phytother Res. 2003;17(10):1209-14.
Esmail F, Farhad Rahmani N, Mehrtash M, Fatemeh Sa-
dat M, Jalilvand M, e eects of 8-week Nigella sativa
supplementation and aerobic training on lipid prole
and VO2 max in sedentary overweight females. Int J
Prev Med. 2014;5(2):210-6.
... The anti-diabetic, anti-hypertensive, cardio-protective, and broncho-dilatory properties of HNS might make it even more beneficial in diabetic, hypertensive, cardiac, and asthmatic patients, which have a higher COVID-19 associated mortality (Cianciosi et al., 2018;Tavakkoli et al., 2017). Furthermore, the anti-platelet and anticoagulant effects of HNS may also shield COVID-19 patients from thromboembolic complications, which are among the leading complications and causes of mortality (Ahmed et al., 2011). ...
... Furthermore, the anti-platelet and anticoagulant effects of HNS may also shield COVID-19 patients from thromboembolic complications, which are among the leading complications and causes of mortality (Ahmed et al., 2011). The hepato-and renoprotective nature of HNS may offer added precedence over other drugs in limiting COVID-19-related hepatic and renal injuries (Cianciosi et al., 2018;Tavakkoli et al., 2017). Anti-pyretic, analgesic, and antitussive properties of HNS can also provide symptomatic relief (Abuelgasim et al., 2021). ...
Until now, no specific and effective treatment exists for coronavirus disease 2019 (COVID‐19). Since honey and Nigella sativa (HNS) have established antiviral, antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, we tested their efficacy for this disease in a multicenter, placebo‐controlled, and randomized clinical trial at four medical care facilities in Pakistan. RT‐PCR confirmed COVID‐19 adults showing moderate or severe disease were enrolled in the trial. Patients were randomly assigned in a 1:1 ratio to receive either honey (1 g kg−1 day−1) and Nigella sativa seeds (80 mg kg−1 day−1) or a placebo for up to 13 days along with standard care. The outcomes included symptoms' alleviation, viral clearance, and 30‐day mortality in the intention‐to‐treat population. Three hundred and thirteen patients, 210 with moderate and 103 with severe disease, underwent randomization from April 30 to July 29, 2020. Among the moderate cases, 107 were assigned to HNS, whereas 103 were assigned to the placebo group. Among the severe cases, 50 were given HNS, and 53 were given the placebo. HNS resulted in ~50% reduction in time taken to alleviate symptoms as compared to placebo (moderate cases: 4 vs. 7 days, Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23–8.84, p < 0.0001 and for severe cases: 6 vs. 13 days, HR: 4.04; 95% CI: 2.46–6.64; p < 0.0001). HNS also cleared the virus earlier than placebo in both moderate cases (6 vs. 10 days, HR: 5.53; 95% CI: 3.76–8.14, p < 0.0001) and severe cases (8.5 vs. 12 days, HR: 4.32; 95% CI: 2.62–7.13, p < 0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% vs. 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03–0.13, p < 0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01–0.09, p < 0.0001). In severe cases, the mortality rate was less than 1/4th in the HNS group than in placebo (4% vs. 18.87%, OR: 0.18; 95% CI: 0.02–0.92, p = 0.029). No HNS‐related adverse effects were observed. HNS, compared with placebo, significantly improved symptoms, expedited viral load clearance, and reduced mortality in COVID‐19 patients. This trial was registered on April 15, 2020 with Identifier: NCT04347382.
... Studies have also suggested that certain diseases of the kidney and liver, in addition to neurobehavioral disorders, can be prevented with optimum utilization of black cumin and TQ. Results from various clinical trials also exhibited therapeutic benefits of TQ on numerous diseases of the skeletal system, cardiovascular system, respiratory system, nervous system, gastrointestinal system, and reproductive system, as well as skin diseases [19,47]. Numerous in vitro and in vivo studies have demonstrated the therapeutic benefits of TQ and black cumin [45,46]. ...
... Studies have also suggested that certain diseases of the kidney and liver, in addition to neurobehavioral disorders, can be prevented with optimum utilization of black cumin and TQ. Results from various clinical trials also exhibited therapeutic benefits of TQ on numerous diseases of the skeletal system, cardiovascular system, respiratory system, nervous system, gastrointestinal system, and reproductive system, as well as skin diseases [19,47]. ...
Full-text available
Osteoporosis, a chronic bone disorder, is one of the leading causes of fracture and morbidity risk. Numerous medicinally important herbs have been evaluated for their efficacy in improving bone mass density in exhaustive preclinical and limited clinical studies. Nigella sativa L. has been used as local folk medicine, and traditional healers have used it to manage various ailments. Its reported beneficial effects include controlling bone and joint diseases. The present manuscript aimed to provide a sound discussion on the pharmacological evidence of N. sativa and its active constituent, thymoquinone, for its utility in the effective management of osteoporosis. N. sativa is reported to possess anti-IL-1 and anti-TNF-a-mediated anti-inflammatory effects, leading to positive effects on bone turnover markers, such as alkaline phosphatase and tartrate-resistant acid phosphatase. It is reported to stimulate bone regeneration by prompting osteoblast proliferation, ossification, and decreasing osteoclast cells. Thymoquinone from N. sativa has exhibited an antioxidant effect on bone tissue by reducing the FeNTA-induced oxidative stress. The present manuscript highlights phytochemistry, pharmacological effect, and the important mechanistic perspective of N. sativa and its active constituents for the management of osteoporosis. Further, it also provides sound discussion on the utilization of a nanotechnology-mediated drug delivery approach as a promising strategy to improve the therapeutic performance of N. sativa and its active constituent, thymoquinone, in the effective management of osteoporosis.
... Black seed has several therapeutic benefits, such as anti-cancer, antimicrobial, analgesic, antipyretic, anti-tussive, anti-inflammatory and anti oxidant potentials. Black seed's antimicrobial effects include those on gram negative and gram-positive bacteria, parasites, viruses and fungi (31) . ...
... [ Downloaded from on 2022-[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] ...
Full-text available
Background and purpose: Myelin degradation is one of the main causes of some neurological diseases. There is growing evidence that plant essential oils may reduce the risk of demyelination. In this experimental study, using a lipidomics approach, we investigated whether administration of Nigella sativa (NS) essential oil could improve changes in the profile of spinal fatty acids in demyelination model induced by intra-spinal administration of ethidium bromide (EB) in mice. Materials and methods: In this experimental study, 30 male rats were studied in five groups (n=6). The groups included control without treatment, solvent, and black seed essential oil (2, 5, and 10 ml/kg, intraperitoneally). The essential oil of NS was prepared and its fatty acid composition was determined by gas chromatography-mass spectrometry (GC-MS). The animals underwent intra-spinal administration of ET 0.2%. At the end of the experiments, samples were taken from the spinal cord of the rats and the concentration of seven different types of fatty acids in the homogenate of the spinal cord was measured and compared between the groups. Results: Ethidium bromide disturbed the normal concentration of polyunsaturated fatty acids, increased arachidonic acid derivatives, and decreased docosahexaenoic acid in rat spinal cord. Treatment with NS essential oil significantly prevented these changes in a dose-dependent manner (P<0.01). Conclusion: NS essential oil protects against EB-induced demyelination by regulating the level of endogenous fatty acids in spinal tissue.
... TQ, as the most abundant component of the essential oil of black cumin (N. sativa) seeds, has properties such as antimicrobial, antinociceptive, anti-epileptic, hypoglycemic, hypolipidemic, and bronchodilator properties (Tavakkoli et al. 2017). TQ exhibits a variety of pharmacological activities including nephroprotection, gastroprotection, anti-hepatocellular carcinoma, cardioprotection, neuroprotection, anti-allergy, retinal protection, bladder protection, reproductive system protection, and respiratory protection (Talebi et al. 2021;Tastemir Korkmaz et al. 2021). ...
Full-text available
Valproic acid (VA), widely used as an antiepileptic, causes structural and functional kidney disorders. Whether thymoquinone (TQ) has a beneficial effect on VA-induced nephrotoxicity has been investigated. Twenty-one male Spraque Dawley rats were grouped into control, VA, and VA + TQ groups (n=7 for per group). VA (500 mg/kg/day) and TQ (50 mg/kg/day) were applied to the rats orally for 14 days. They were euthanized on the 15th day of the treatment. The cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) gene expression levels, biochemical parameters, total antioxidant/oxidant statuses (TAS/TOS), oxidative stress index (OSI), histological and immunohistochemical analysis were performed to evaluate kidney toxicity. In the VA + TQ group, COX-1 expression levels increased, while COX-2 expression levels decreased. While the creatinine (Cr) and blood urea nitrogen (BUN) levels, production of caspase-3 (CAS-3) and NADPH oxidase-4 (NOX-4) were increased in the VA-treated group, they were decreased in VA + TQ group. Treatment with TQ against VA administration decreased TOS and OSI levels while increasing TAS. TQ protects the kidney against the toxic effects of VA.
... Black seed or black cumin (Nigella sativa), which belongs to the Ranunculacea family, is an annual herb with many pharmacological properties [9]. Black cumin is native to a vast region of the eastern Mediterranean, northern Africa, the Indian subcontinent, and Southwest Asia, and is cultivated in many countries, including Egypt, Iran, Greece, Syria, Albania, Turkey, Saudi Arabia, India, and Pakistan [10]. ...
pH represents the concentration of free H+ in pine needles extracts (PNE) and is therefore an important initial parameter in quality control. Electrical conductivity and pH of samples of fresh and stored for 20 days of PNE with black cumin oil and olive oil had values of 0.00 due to the encapsulation of water molecules, pH and electrical conduction was not possible. The pH of the other samples was in a weakly acidic environment because the pH of natural pine needles is 3.8. Electrical conductivity values in all samples except pine needle extract and honey increased during storage. By monitoring the parameters of pH and electrical conductivity in the quality control of PNE, it gives us a significant insight into the physical state of the phases and the way of storage.
Full-text available
Black seeds, sometimes called black cumin, are obtained from the spicy medicinal herb Nigella sativa that is native to a broad region encompassing the eastern Mediterranean, southwest Asia, and northern Africa. The seed and its oil have a distinctive aroma and taste, diversely described as bitter, peppery, metallic, and pungent. Both are frequent ingredients in numerous foods, especially in the Middle East and India. In these same regions N sativa has an extensive history as a folk medicine dating back millenia for relief for a variety of health conditions such as asthma, headache, bronchitis, amenorrhea, allergies, infections, and hypertension. The antioxidant, anti-inflammatory, and immunomodulatory properties of N sativa seeds observed in preclinical studies provided an impetus for clinical trials examining the seeds' effects on cardiovascular, respiratory, and neurological disorders, among others. This narrative review summarizes findings from publications addressing several these and other disorders and provides suggestions for future research.
Full-text available
Background: Hypothyroidism has been linked to many testicular structural and dysfunctional changes in males. Thymoquinone (TQ) has shown a potent testicular protective effect through its antioxidant, anti-inflammatory, antiapoptotic, fertility-enhancing, and endocrine modulatory activities. Objectives: This study aimed to investigate the efficacy of TQ in preserving the testicular structure of a model of experimentally induced hypothyroidism in rats and identify the mechanism behind this effect. Materials and methods: Propylthiouracil (PTU) was used to induce hypothyroidism in adult male Wistar rats, who were then treated with TQ (50 mg/kg/body weight) for 4 weeks and compared to the untreated rats. Thyroid hormonal profile, oxidants/antioxidants profile, and serum testosterone levels were assessed. Gene expression and immune expression of SIRT1 and pro-inflammatory cytokines TNF-α and NF-κB were also assessed in the testicular tissue. Results: TQ administration successfully improved PTU-induced disturbance in the thyroid hormonal profile (T3, T4, and TSH), serum testosterone level, and pancreatic antioxidants compared to the untreated hypothyroid group. TQ significantly downregulated ( p = 0.001, p ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated ( p = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased ( p = 0.002, p = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased ( p ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased ( p ˂ 0.001) in the testes of TQ-treated hypothyroid rats. Conclusion: Thymoquinone could limit the hypothyroidism-induced structural changes in the testis, mostly through the upregulation of SIRT1 expression, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects that were evident in this study. Therefore, TQ is recommended as an adjuvant safe supplement in managing hypothyroidism, especially in males.
Full-text available
From Wuhan to almost all parts of the globe, the deadly corona virus (COVID-19) hard-hit humanity like no other deadly disease has ever. This paper analyses the devastating diverse effects of COVID-19on various aspects of human life, looking beyond its death and infection plagues on humans across the globe.Drawing from secondary data, observation and intuition, the study reveals heart-blowing infection and death rates, variants and non/survivability factors of COVID-19. Next, it shows that besides reducing world's population and causing global panic and public health challenges, COVID-19 has exerted devastating effects on socioeconomic , psychological, clinical, educational, behavioral, nutritional, personal and general aspects of life. Virtually, all nations of the world were/are affected. Although no cogent or permanent solution has been found, alternative orthodox and traditional (herbal) remedies are so far used for recovering the health of infected persons and for prevention. The lockdown, imposed on nations to control the spread, also brought untold difficult situations and diverse effects upon the citizenry. The peak of the effects is the distortion of normal ways of life, which ushered in uncommon new ways of life that most people still battle with. The study concludes that COVID-19 pandemic, which so far defies absolute remedy, has diverse long-term devastating effects on humans and phenomena across the globe.It recommends the harmonized efforts, research findings and remedies, and the subversion of international politics over COVID-19 with more global cooperation and meaningful strategies among all nations of the globe.
Full-text available
Cyclophosphamide (CYC) has been known as an anticancer drug with several side effects on various organs such as the liver. In this study, the hepatoprotective properties of thymoquinone (TQ) were tested to decrease the damaging effects of Cyclophosphamide on the liver. The objective was to study and observe the possible ameliorative effect of thymoquinone on cyclophosphamide-induced hepatic toxicity in Wistar rats. Thirty Wistar male Adolescent (8 – 9 weeks old) rats weighing 70g – 150g were divided into Six groups; 5 rats per group (n=5) and treated orally for 21 consecutive days. Group A served as the control, and the rats in this group received normal saline. Group B was treated with 20mg/kg of cyclophosphamide. Group C was treated with 5mg/kg of Thymoquinone. Group D was treated with 10mg/kg of Thymoquinone. Group E was treated with 20mg/kg of cyclophosphamide and 5m/kg of Thymoquinone while Group F animals were treated with 20mg/kg of Cyclophosphamide and 10mg/kg of Thymoquinone. The Cyclophosphamide treated group showed significant decreases in the body and liver weight, distorted hepatic cytoarchitecture, and reduction in hepatic function whereas co-treatment with TQ, showed protective effects on Cyclophosphamide-induced hepatotoxicity damage. These results suggest that the administration of Thymoquinone may have a protective potential on Cyclophosphamide induce hepatotoxicity.
Full-text available
Nigella sativa has been used as traditional medicine for centuries. The crude oil and thymoquinone (TQ) extracted from its seeds and oil are effective against many diseases like cancer, cardiovascular complications, diabetes, asthma, kidney disease etc. It is effective against cancer in blood system, lung, kidney, liver, prostate, breast, cervix, skin with much safety. The molecular mechanisms behind its anticancer role is still not clearly understood, however, some studies showed that TQ has antioxidant role and improves body’s defense system, induces apoptosis and controls Akt pathway. Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history of last 2~3 decades. There are not so many research works done with this important traditional medicine and very few reports exist in the scientific database. In this article, we have summarized the actions of TQ and crude oil of N. sativa against different cancers with their molecular mechanisms. Key words: Traditional medicine, Nigella sativa, Thymoquinone, Antioxidant, Anti-cancer mechanism doi: 10.4314/ajtcam.v8i5S.10
Full-text available
Forty one type 2 diabetes mellitus (DM2) patients, selected and registered in accordance with especially laid down criteria were studied for the effect of Nigella sativa oil. All patients consumed Nigella saliva oil for 40 d followed by a placebo for another 40 d. Fasting blood sample of each subject was collected on 0, 40th and 80th day of the study. Glucose, insulin, platelet count, total leukocyte count, ALT, AST and blood urea were analyzed using standard methods. SPSS version-12 was used for statistical analysis and all the phases were compared by paired sample test. A significant fall in fasting blood glucose and rise in insulin and AST levels was observed after treatment with Nigella sativa oil as compared to concurrent control levels. Glucose and insulin levels significantly reversed after the placebo administration. Platelet count, total leukocyte count, ALT and blood urea remained statistically unchanged after Nigella sativa oil treatment or placebo as compared to the baseline levels. It is concluded that Nigella sativa oil may play a role in management of type 2 diabetes with reasonable renal and hepatic safety.
Neuropharmacology is the scientific study of drug effect on nervous system. In the last few years, different natural plants and their active constituents have been used in neurological therapy. The availability, lower price, and less toxic effects of herbal medicines compared with synthetic agents make them as simple and excellent choice in the treatment of nervous diseases. Nigella sativa, which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. In traditional and modern medicines several beneficial properties have been attributed to N. sativa and its main component, thymoquinone (TQ). In this review, various studies in scientific databases regarding the neuropharmacological aspects of N. sativa and TQ have been introduced. Results of these studies showed that N. sativa and TQ have several properties including anticonvulsant, antidepressant, anxiolytic, anti-ischemic, analgesic, antipsychotic, and memory enhancer. Furthermore, its protective effects against neurodegenerative diseases such as Alzheimer, Parkinson and multiple sclerosis have been discussed. Although there are many studies indicating the beneficial actions of this plant in nervous system, the number of research projects relating to the human reports is rare. Copyright © 2016 John Wiley & Sons, Ltd.
The effects of Nigella Sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: -15.65mg/dL, 95% CI: -24.67, -6.63, p=0.001), LDL-C (WMD: -14.10mg/dL, 95% CI: -19.32, -8.88, p<0.001), and triglyceride levels (WMD: -20.64mg/dL, 95% CI: -30.29, -11.00, p<0.001). No significant effect on HDL-C concentrations (WMD: 0.28mg/dL, 95% CI: -1.96, 2.53, p=0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes.
Introduction: The extract of the seeds of Nigella sativa (Ns) has been used therapeutically for centuries as a safe herbal medicine, and has been reported to have beneficial effects in the treatment of diabetic osteopenia and bone healing in animal models. In the present study, we examined the effect of Ns seed oil extract on biochemical bone markers in osteopenic postmenopausal women. Materials and Methods: In a placebo controlled clinical trial, 30 osteopenic postmenopausal women, aged 49-72 years, were randomized to either 3-month Ns (oil) treatment (3cc, 0.05 cc/kg/day p.o.) or placebo groups. In all subjects, calcium-D supplements (1 tab per day) were administered during the 3 month study period. At baseline and after 3 months CBC diff, liver and kidney function tests, and serum levels of calcium and phosphate and plasma levels of bone markers (including CTX,Osteocalcin and Bone-ALP) were measured. Results: Twenty-two participants completed the 3 month study period (9 in the Ns group and 13 in the placebo group). Women in the placebo group had relatively higher BMI in comparison with those in the Ns group. Other characteristics and bone markers levels were similar between two groups at the baseline. Plasma levels of bone markers including CTX, Osteocalcin and Bone ALP did not differ significantly between the Ns and placebo groups at the end of the 3 months; neither did changes in bone markers over the course of study show statistically significant differences between the two groups. Conclusion: Although Ns oil was safe, no reports of adverse reactions were observed in this study, we found no beneficial effect of Ns treatment on bone turnover markers. Based on our results, we do not recommend it for the prevention or treatment of bone loss. However this needs to be further investigated in the long-term clinical trials and with larger sample sizes.
The immune status of 27 patients with inhalation allergy was examined before and after a black cumin oil therapy lasting an average of 82 days in a retrospective study. We determined cellular immune status, circulating immune complexes and the subjective change of the inhalation allergy symptoms. All patients received a standard dosage of 6 capsules containing 420 mg black cumin oil each per day. The absolute cell count of the natural killer cells has risen tendentiously for 15% and we also measured a tendentiously increase of 9% lymphocytes out of the leucocyte cell population. The other lab parameters did not change significantly. Ten patients reported an improvement of subjective allergy symptoms.
Newly diagnosed acute lymphoblastic leukemia (ALL) patients were randomly divided into Groups I-III; having 21, 20 and 21 patients each, respectively. Ten age, sex and socio-economically matched healthy subjects were included for reference. Blood samples were taken for hematological parameters. In all groups these procedures were repeated after every 0.5 month till 6 months (including first 3 months of completion of induction chemotherapy followed by maintenance therapy. Due to various reasons, 48 subjects (16 in each) completed the study and their data were analyzed. In conventional therapy (Group I), daunorubicin (1.5mg/kg,i/v weekly), vincristine (.4mg/kg i/v twice weekly) and prednisolone (5 mg/kg per day orally in 3 divided doses) were prescribed to patients of ALL as induction therapy for a period of 3 months. In Group II, L-asparaginase was administered in addition to Group I therapy in 100u/kg, i/m twice weekly dose. Powdered Nigella sativa seeds were given to Group III patients in addition to conventional therapy (without L-asparaginase) in 40 mg/kg orally in two equally divided doses. The data showed that prognosis was good in all groups and was similar in male and female. Remission rate (RR) was affected by increasing age and survival was better in younger patients. The prognosis was worse in patients with high (>50000/mm3) initial WBC counts. RR was negatively affected by severe anemia (Hb<8.0g/dl) which showed positive correlation with Hb level. ESR was markedly raised in majority of patients at presentation but remained high even after induction therapy. The RR and survival time were better in patients having blood ESR between 10 t o 100 mm/1st hr.
Two ways cross-over comparative study was carried out to evaluate the differences between the biological effects of two-weeks administration of Nigella sativa seeds and total oil on blood glucose, cholesterol, triglycerides and prolactin levels. Blood RBCs, WBCs and platelets counts and hemoglobin level (Hb) were also determined. The effect on some enzyme activities as alanine amino-transferase (ALT), aspartate aminotransferase (AST), alkaline phophatase (ALP) gamma glutamyl-transferase (γ-GT) and creatine kinase (CK) activities were also determined. The study was carried out on healthy female volunteers of an average age 22 ± 0.08 years. The results showed that: (a) Both crushed seeds and the formulated total oil produced a significant decrease in glucose, prolactin, triglycerides and cholesterol level (b) The crushed seeds showed a significant increase in WBCs and hemoglobin level (P ≤ 0.05), where as the formulated total oil showed a significant increase in hemoglobin level (P ≤ 0.01) (c) Only the total oil showed a significant increase in ALT (P ≤ 0.05) and AST (P ≤ 0.001), while both the oil and the crushed seeds showed significant increase in γ-GT and ALP activities.
The effect of 2 weeks daily treatment with 2 g Nigella sativa (N. sativa) on the blood levels of glucose, uric acid, cholesterol, triglycerides, BUN and creatinine was studied on 16 second year male medical students. Nine students took 2 capsules of 500 mg N. sativa twice daily and served as the test group. Seven students served as controls and took 2 capsules of 500 mg brown sugar twice daily. In the test group, the parameters which showed a significant decrease by the end of the first week of treatment were glucose (p < 0.01) and cholesterol (p = 0.05). However, both levels went up by the end of the second week of the treatment but remained below baseline. Creatinine was significantly elevated (p < 0.01) by the end of the first week. Uric acid showed a progressive but a nonsignificant decrease. A finding of interest was that the control group showed a progressive and significant increase in uric acid. It is concluded that N. sativa has a potential reducing effect on the blood levels of both glucose and cholesterol.